Claims for Patent: 10,435,472

Summary for Patent: 10,435,472

Title:	Method of treating bone metastasis diseases, medicaments therefore, and a method of predicting the clinical outcome of treating bone metastasis diseases
Abstract:	The instant invention provides for a new method of treating bone metastasis diseases in subjects, wherein said method preferably depends on whether the subject shows certain specific proteins levels in one or more body fluids prior to or during treatment, wherein said treatment comprises the administration of at least one pan .alpha.v integrin inhibitor to a subject, a medicament for use in said new methods, and a method of predicting the outcome of a treatment with at least one pan .alpha.v integrin inhibitor based on said specific protein levels in one or more body fluids of the subject.
Inventor(s):	Straub; Josef (Seeheim-Jugenheim, DE), Staub; Eike (Darmstadt, DE)
Assignee:	Merck Patent GmbH (Darmstadt, DE)
Application Number:	15/511,959
Patent Claims:	1. A method for identifying a tumour in a subject likely to benefit from treatment with pan .alpha.v integrin inhibitor Abituzumab, said method comprising: determining the levels of two or more proteins selected from the group consisting of DCN, F5, ICAM3, STK17B, STX1A, TEK, ANG, LEPR, MAP2K2, MAPK11, RGMB, and TNFRSF17 in at least one body fluid of said subject, wherein: a) a high level of one or more proteins selected from the group consisting of: DCN, F5, ICAM3, PIGR, STK17B, STX1A, and TEK, and/or b) low levels of one or more proteins in at last one body fluid of said subject, wherein said one or more proteins are selected from the group consisting of: ANG, LEPR, MAP2K2, MAPK11, RGMB, and TNFRSF17; and identify a tumour likely to benefit from the treatment with the pan .alpha.v integrin inhibitor Abituzumab; and treating said subject with Abituzumab. 2. A method for identifying a tumour in a subject likely to benefit from treatment with the pan .alpha.v integrin inhibitor Abituzumab, said method comprising: determining a level of a STX1A protein in one or more body fluids of said subject, wherein a high level thereof identifies a tumour likely to benefit from the treatment with the pan .alpha.v integrin inhibitor Abituzumab; and treating said subject with Abituzumab. 3. The method according to claim 1, wherein the level of a respective protein in said at least one body fluid is a) classified as high, if the respective protein level in said at least one body fluid is at least 5% higher than a median threshold determined for the respective protein, and/or b) classified as low, if the respective protein level in said at least one body fluid is at least 5% lower than said median threshold determined for the respective protein. 4. The method according to claim 1, wherein the at least one body fluid comprises blood plasma or consist of blood plasma. 5. A method for identifying a subject responsive to treatment with pan .alpha.v integrin inhibitor Abituzumab, said method comprising: determining the levels of two or more proteins selected from the group consisting of DCN, F5, ICAM3, PIGR, STK17B, STX1A TEK, ANG, LEPR, MAP2K2, MAPK11, RGMB, and TNFRSF17in at least one body fluid of said subject, wherein: a) a high level of one or more proteins selected from the group consisting of: DCN, F5, ICAM3, PIGR, STK17B, STX1A, and TEK, and/or b) low levels of one or more proteins in at last one body fluid of said subject, wherein said one or more proteins are selected from the group consisting of: ANG, LEPR, MAP2K2, MAPK11, RGMB, and TNFRSF17; identify a subject responsive to treatment with the pan .alpha.v integrin inhibitor Abituzumab; and treating said subject with Abituzumab. 6. The method according to claim 1, wherein said at least one body fluid is blood plasma. 7. The method according to claim 1, wherein the Abituzumab is administered to said subject every week, every second week or every fourth week. 8. The method according to claim 2, wherein the level of said STX1A protein in at least one body fluid sample of said subject is classified as high if the respective specific protein level in the one or more body fluid is at least 5% higher than a median threshold determined for STX1A protein. 9. The method according to claim 3, wherein said median threshold is determined in a subject population having bone metastasis disease. 10. The method according to claim 1, wherein said subject is characterized by a high level of the protein: STX1A and/or a protein having at least 90% sequence homology to said STX1A protein. 11. The method according to claim 1, wherein said subject is characterized by the respective levels of one or more proteins having at least 90% sequence homology to said two or more proteins. 12. The method according to claim 1, wherein said at least one body fluid is selected from the group consisting of blood plasma, blood serum and whole blood. 13. The method according to claim 3, wherein high levels and/or low levels of said two or more proteins are present and/or determined prior to administering said pan .alpha.v integrin inhibitor Abituzumab. 14. The method according to claim 3, wherein high levels and/or low levels of said two or more proteins are present and/or determined during or after administering said pan .alpha.v integrin inhibitor Abituzumab. 15. The method according to claim 9, wherein the bone metastasis disease is cancer or is derived from cancer. 16. The method according to claim 9, wherein the bone metastasis disease is derived from prostate cancer, breast cancer and/or lung cancer. 17. The method according to claim 9, wherein said median threshold for the respective specific protein is determined from body fluid of a plurality of subjects being part of a diseased subject population suffering from the respective bone metastasis disease. 18. The method according to claim 1, wherein said Abituzumab is administered to said subject in an amount of 100 mg to 3000 mg per month. 19. The method according to claim 1, wherein the Abituzumab is administered to said subject in an amount of 500 to 2000 mg every week, every second week every or every fourth week. 20. The method according to claim 1, wherein the Abituzumab is administered to said subject in an amount of about 500 mg per week, about 750 mg per week, about 1000 mg per week or about 1500 mg per week. 21. The method according to claim 1, wherein said pan .alpha.v integrin inhibitor Abituzumab is administered in combination with one or more agents or chemotherapeutic agents: a) selected from the group consisting of Leuproreline, Leuproreline acetate, bicalutamide, nilutamide, triptoreline, gosereline, flutamide, cyproterone, busereline and degarelix, b) selected from the group consisting of Zoledronic acid, Pamidronic acid, Clodronate disodium, Alendronic acid and Ibandronic acid, and/or c) selected from the group consisting of Abiraterone, Abiraterone acetate, Prednisone, Enzalutamide, Radium Ra 223 dichloride, Docetaxel, Sipuleucel-T, Cabazitaxel and Mitoxantrone; and/or the pharmaceutically acceptable derivatives and/or salts thereof. 22. The method according to claim 1, wherein said pan .alpha.v integrin inhibitor Abituzumab is administered in combination with 1, 2 or 3 agents or chemotherapeutic agents, selected from the group consisting of: a) Leuproreline, Leuproreline acetate, bicalutamid, nilutamide, triptoreline, gosereline, flutamide, cyproterone, busereline and degarelix, and/or the pharmaceutically acceptable derivatives and/or salts thereof; and/or b) Zoledronic acid, Pamidronic acid, Clodronate disodium, Alendronic acid and Ibandronic acid, and/or the pharmaceutically acceptable derivatives and/or salts thereof. 23. The method according to claim 5, wherein the level of protein in said at least one body fluid is a) classified as high, if the respective protein level in said at least one body fluid is at least 5% higher than a median threshold determined for the respective protein, and/or b) classified as low, if the respective protein level in said at least one body fluid is at least 5% lower than said median threshold determined for the respective protein.

Details for Patent 10,435,472

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Dendreon Pharmaceuticals Llc	PROVENGE	sipuleucel-t	Injection	125197	04/29/2010		2034-09-17