Claims for Patent: 10,001,483

Summary for Patent: 10,001,483

Title:	Methods for the treatment of Kaposi\'s sarcoma or KSHV-induced lymphoma using immunomodulatory compounds, and uses of biomarkers
Abstract:	Provided herein are uses of gene and protein biomarkers as a predictor of clinical sensitivity of Kaposi\'s sarcoma (KS) or Kaposi\'s sarcoma-associated herpesvirus (KSHV) induced lymphoma and patient response to treatment with an immunomodulatory compound. Further provided herein are methods for the treatment or management of Kaposi\'s sarcoma or KSHV-induced lymphoma with an immunomodulatory compound, alone or in combination with doxorubicin.
Inventor(s):	Yarchoan; Robert (Bethesda, MD), Zeldis; Jerome B. (Princeton, NJ), Polizzotto; Mark N. (New South Wales, AU), Davis; David A. (Bethesda, MD), Sereti; Irini (Washington, DC), Uldrick; Thomas S. (Washington, DC), Whitby; Denise (Frederick, MD), Khetani; Vikram (Short Hills, NJ)
Assignee:	Celgene Corporation (Summit, NJ) The United States of America, as Represented by the Secretary, Department of Health and Human Services (Washington, DC)
Application Number:	15/192,819
Patent Claims:	1. A method of treating or managing Kaposi's sarcoma-associated herpesvirus (KSHV) induced lymphoma, comprising: identifying a patient having KSHV-induced lymphoma sensitive to treatment with a compound of the formula: ##STR00056## or a pharmaceutically acceptable salt, solvate or stereoisomer thereof; wherein said identifying comprises measuring a level of major histocompatibility complex class I (MHC-1) in a biological sample obtained from the patient, wherein a decreased level of MHC-1 relative to a control sample indicates a likelihood that the patient is sensitive to treatment with the compound; and (ii) administering to the patient a therapeutically effective amount of the compound in a 28 day cycle comprising 21 consecutive days of administration followed by seven consecutive days of rest. 2. The method of claim 1, wherein the KSHV-induced lymphoma is a B-cell lymphoma. 3. The method of claim 2, wherein the B-cell lymphoma is primary effusion lymphoma (PEL). 4. The method of claim 1, wherein KSHV-induced lymphoma is multicentric Castleman's disease (MCD). 5. The method of claim 1, wherein the patient is human immunodeficiency virus (HIV) positive. 6. The method of claim 1, wherein the KSHV-induced lymphoma is newly diagnosed, relapsed, refractory, or relapsed and refractory. 7. The method of claim 1, wherein the patient has received previous therapy for KSHV-induced lymphoma. 8. The method of claim 7, wherein the previous therapy is treatment with cytotoxic chemotherapy, treatment with radiation therapy, treatment with an immunomodulatory compound, treatment with interferon, or treatment with local therapy. 9. The method of claim 8, wherein the previous therapy is treatment with thalidomide, lenalidomide, or a combination thereof. 10. The method of claim 1, wherein the compound is administered in an amount of about 1, 2, 3, 4, or 5 mg per day. 11. The method of claim 1, wherein the compound is administered as a free base. 12. The method of claim 1, wherein the compound is administered orally. 13. The method of claim 12, wherein the compound is administered in a capsule or tablet. 14. The method of claim 1, which further comprises administering a therapeutically effective amount of an additional active agent, wherein the additional active agent is doxorubicin, a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor. 15. The method of claim 14, wherein the additional active agent is a PD-1 inhibitor or a PD-L1 inhibitor. 16. The method of claim 15, wherein the PD-1 inhibitor is nivolumab, pembrolizumab, pidilizumab, REGN2810, PDR 001, AMP-224, or MEDI0680. 17. The method of claim 15, wherein the PD-L1 inhibitor is durvalumab, avelumab, atezolizumab, or BMS-936559. 18. The method of claim 3, wherein the patient is human immunodeficiency virus (HIV) positive. 19. The method of claim 3, wherein the patient has received previous treatment with cytotoxic chemotherapy, radiation therapy, an immunomodulatory compound, interferon, or local therapy. 20. The method of claim 19, wherein the previous therapy is treatment with thalidomide, lenalidomide, or a combination thereof. 21. The method of claim 3, wherein the compound is administered in an amount of about 1, 2, 3, 4, or 5 mg per day. 22. The method of claim 21, wherein the compound is administered as a free base. 23. The method of claim 21, wherein the compound is administered orally. 24. The method of claim 23, wherein the compound is administered in a capsule or tablet. 25. The method of claim 3, wherein the compound is orally administered in an amount of 5 mg per day for 21 consecutive days followed by seven consecutive days of rest in a 28 day cycle. 26. The method of claim 3, which further comprises administering a therapeutically effective amount of an additional active agent, wherein the additional active agent is doxorubicin, a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor. 27. The method of claim 26, wherein the additional active agent is a PD-1 inhibitor or a PD-L1 inhibitor. 28. The method of claim 27, wherein the PD-1 inhibitor is nivolumab, pembrolizumab, pidilizumab, REGN2810, PDR 001, AMP-224, or MEDI0680. 29. The method of claim 27, wherein the PD-L1 inhibitor is durvalumab, avelumab, atezolizumab, or BMS-936559.

Details for Patent 10,001,483

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Llc	KEYTRUDA	pembrolizumab	For Injection	125514	September 04, 2014		2035-06-26
Merck Sharp & Dohme Llc	KEYTRUDA	pembrolizumab	Injection	125514	January 15, 2015		2035-06-26
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	December 22, 2014		2035-06-26