Claims for Patent: 10,358,496

Summary for Patent: 10,358,496

Title:	Low dose immune checkpoint blockade in metastatic cancer
Abstract:	A method of treating cancer comprising and reducing autoimmune side effects in administration of anti-CTLA-4 antibodies. The invention provides methods for low dose immune checkpoint (IC) treatment of metastatic cancer by delivering anti-CTLA-4 and anti-PD-1 antibodies to cancer patients. Methods also provide for IL-2 stimulation for the activation of T cells against tumor cells. The invention further provides methods for daily cyclic high fever response (hyperthermia) during IL-2 therapy. The methods provide treatment of metastatic cancer without unacceptable autoimmune side effects.
Inventor(s):	Bakacs; Tibor (Budapest, HU), Kleef; Ralf (Vienna, AT)
Assignee:	Kleef; Ralf (Vienna, AT)
Application Number:	15/443,589
Patent Claims:	1. A method for reducing autoimmune side effects, said method comprising administering 0.5 mg/kg or lower dose of anti-PD-1 antibody with co-administration of 0.3 mg/kg or lower dose of anti-CTLA-4 antibody to a patient anticipating or experiencing anti-CTLA-4 autoimmune side effects or anti-PD-1 autoimmune side effects, wherein the anti-CTLA-4 antibody is ipilimumab and the anti-PD-1 antibody is nivolumab, pembrolizumab or pidilizumab, said method further comprising administering to the patient 300 mg/m.sup.2 or lower dose of cyclophosphamide. 2. The method of claim 1 for reducing autoimmune side effects in administration of anti-CTLA-4 antibodies by administering an effective amount of anti-PD-1 antibody to a patient anticipating or experiencing anti-CTLA-4 autoimmune side effects. 3. The method of claim 1 for reducing autoimmune side effects in administration of anti-PD-1 antibodies by administering an effective amount of anti-CTLA-4 antibody to a patient anticipating or experiencing anti-PD-1 autoimmune side effects. 4. The method of claim 1, further comprising administering Taurolidine to the patient, wherein the patient is being treated with high-dose (HD) IL-2. 5. The method of claim 1, wherein the patient is being treated with hyperthermia. 6. The method of claim 1, comprising weekly administering to the patient in need 0.5 mg/kg dose of anti-PD-1 antibody with co-administration of 0.3 mg/kg dose of anti-CTLA-4 antibody. 7. A method for enhancing cancer immunity in a patient while reducing autoimmunity in said patient comprising administering 0.5 mg/kg or lower dose of anti-PD-1 antibody with co-administration of 0.3 mg/kg or lower dose of anti-CTLA-4 antibody to a patient in need of treatment, wherein the anti-CTLA-4 antibody is ipilimumab and the anti-PD-1 antibody is nivolumab, pembrolizumab or pidilizumab, said method further comprising administering to the patient in need 300 mg/m lower dose of cyclophosphamide. 8. The method of claim 7, further comprising administering Taurolidine to the patient, wherein the patient is being treated with high-dose (HD) IL-2. 9. The method of claim 7, wherein the patient is being treated with hyperthermia. 10. The method of claim 7, comprising weekly administering to the patient in need 0.5 mg/kg dose of anti-PD-1 antibody with co-administration of 0.3 mg/kg dose of anti-CTLA-4 antibody. 11. The method of claim 7, wherein the anti-PD-1 antibody and anti-CTLA-4 antibody are administered simultaneously. 12. The method of claim 7, wherein the anti-PD-1 antibody and anti-CTLA-4 antibody are administered at different times. 13. The method of claim 7 comprising administering to a patient in need anti-PD-1 antibody and anti-CTLA-4 antibody in amounts effective to produce an anti-cancer effect, wherein the administration of anti-PD-1 antibody and anti-CTLA-4 antibody results in a lower level of autoimmunity as compared to administration of either anti-CTLA-4 or anti-PD-1 antibody alone. 14. The method of claim 13, wherein the anti-cancer effect is an effect chosen from decreased tumor burden, decreased metastasis, decreased tumor growth, and reduction in new tumor formation.

Details for Patent 10,358,496

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2036-03-01
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2036-03-01
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2036-03-01
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	12/22/2014		2036-03-01
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	10/04/2017		2036-03-01