Claims for Patent: 9,534,052

Summary for Patent: 9,534,052

Title:	Reducing systemic regulatory T cell levels or activity for treatment of Alzheimer\'s disease
Abstract:	A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session.
Inventor(s):	Eisenbach-Schwartz; Michal (Rehovot, IL), Baruch; Kuti (Rehovot, IL), Rosenzweig; Neta (Rehovot, IL)
Assignee:	Yeda Research and Development Co. Ltd (Rehovot, IL)
Application Number:	15/212,231
Patent Claims:	1. A method of treating an Alzheimer's Disease, the method comprising administering to an individual in need thereof a composition comprising a human neutralizing anti-programmed death-1 (PD-1) antibody or a humanized, neutralizing anti-PD-1 antibody, wherein the composition is administered by a dosage regime comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session where the composition is administered to the individual followed by a non-treatment period where the composition is not administered to the individual, and wherein the non-treatment period is longer than the treatment session; wherein, if administration of the composition during the treatment session is a repeated administration, the non-treatment period is longer than the period between repeated administrations during the treatment session; wherein administration of the composition transiently reduces levels of systemic immunosuppression and increases choroid plexus gateway activity in facilitating selective recruitment of immune cells into the central nervous system, thereby treating the individual. 2. The method according to claim 1, wherein the administration of the composition during the treatment session is a single administration. 3. The method according to claim 1, wherein the administration of the composition during the treatment session is a repeated administration. 4. The method according to claim 3, wherein the repeated administration occurs once every two, three, four, five or six days. 5. The method according to claim 3, wherein the repeated administration occurs once weekly. 6. The method according to claim 3, wherein the repeated administration occurs once every four weeks. 7. The method according to claim 1, wherein the treatment session is from 3 days to four weeks. 8. The method according to claim 7, wherein the treatment session is from one week to four weeks. 9. The method according to claim 1, wherein the non-treatment period is longer than the treatment session. 10. The method according to claim 9, wherein the non-treatment period is from one week to six months. 11. The method according to claim 1, wherein the human neutralizing anti-programmed death-1 (PD-1) antibody is nivolumab, BMS-936559, MPDL3280A or MSB0010718C. 12. The method according to claim 1, wherein the humanized, neutralizing anti-PD-1 antibody is pidilizumab, pembrolizumab, AMP-224, MED14736 or MED10680. 13. The method according to claim 1, wherein the transient reduction in the level of systemic immunosuppression is associated with an increase in a systemic presence or activity of IFN.gamma.-producing leukocytes and/or an increase in a systemic presence or activity of an IFN.gamma. cytokine. 14. The method according to claim 1, wherein the transient reduction in the level of systemic immunosuppression is associated with an increase in a systemic presence or activity of effector T cells. 15. The method according to claim 1, wherein the transient reduction in the level of systemic immunosuppression is associated with a decrease in a systemic presence or activity of regulatory T cells and/or a decrease in a systemic presence of an IL-10 cytokine. 16. The method according to claim 1, wherein the transient reduction in the level of systemic immunosuppression is associated with a decrease in a systemic presence of myeloid-derived suppressor cells (MDSCs). 17. The method according to claim 1, wherein the transient reduction in the level of systemic immunosuppression occurs by release of a restraint imposed on the immune system by one or more immune checkpoints. 18. The method according to claim 17, wherein administration of the composition blocks the one or more immune checkpoints, thereby causing the transient reduction in the level of systemic immunosuppression. 19. The method according to claim 18, wherein the one or more immune checkpoints includes PD1-PDL1 or PD1-PDL2. 20. The method according to claim 1, wherein the administration of the composition during the treatment session is maintained at least until a systemic presence or activity of IFN.gamma.-producing leukocytes and/or an IFN.gamma. cytokine rises above a reference, at which point the administration is stopped, and the non-treatment period is maintained as long as the systemic presence or activity of IFN.gamma.-producing leukocytes and/or an IFN.gamma. cytokine is above the reference, wherein the reference includes a) a level of a systemic presence or activity of IFN.gamma.-producing leukocytes and/or an IFN.gamma. cytokine measured in the most recent blood sample obtained from the individual before the administering; or b) a level of a systemic presence or activity of IFN.gamma.-producing leukocytes and/or an IFN.gamma. cytokine characteristic of a population of individuals afflicted with the Alzheimer's Disease. 21. The method according to claim 1, wherein a cerebral level of soluble amyloid beta peptide is reduced in the individual, a cerebral amyloid beta (A.beta.) plaque burden is reduced or cleared in the individual, a hippocampal gliosis is reduced in the individual, a cerebral level of a pro-inflammatory cytokine is reduced in the individual, a brain inflammation is decreased in the individual and/or a cognitive function is improved in the individual. 22. The method according to claim 21, wherein the improved cognitive function is learning, memory, creation of imagery, plasticity, thinking, awareness, reasoning, spatial ability, speech and language skills, language acquisition, capacity for judgment attention or any combination thereof. 23. The method according to claim 1, wherein the immune cells include monocytes, macrophages, or T cells. 24. The method according to claim 23, wherein the T cells include regulatory T cells. 25. A method of treating an Alzheimer's Disease, the method comprising administering to an individual in need thereof a composition comprising a human neutralizing anti-programmed death-1 (PD-1) antibody or a humanized, neutralizing anti-PD-1 antibody as the only active ingredient, wherein the composition is administered by a dosage regime comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session where the composition is administered to the individual followed by a non-treatment period where the composition is not administered to the individual, and wherein administration of the composition transiently reduces levels of systemic immunosuppression and increases choroid plexus gateway activity in facilitating selective recruitment of immune cells into the central nervous system, thereby treating the individual. 26. The method according to claim 25, wherein the human neutralizing anti-programmed death-1 (PD-1) antibody is nivolumab, BMS-936559, MPDL3280A or MSB0010718C. 27. The method according to claim 25, wherein the humanized, neutralizing anti-PD-1 antibody is pidilizumab, pembrolizumab, AMP-224, MED14736 or MED10680. 28. The method according to claim 25, wherein the non-treatment period is longer than the treatment session. 29. The method according to claim 28, wherein the non-treatment period is from one week to six months. 30. The method according to claim 29, wherein the non-treatment period is from two weeks to six months. 31. The method according to claim 28, wherein the treatment session is from 3 days to four weeks. 32. The method according to claim 30, wherein the non-treatment period is from three weeks to six months. 33. The method according to claim 31, wherein the treatment session is from one week to four weeks. 34. The method according to claim 10, wherein the non-treatment period is from two weeks to six months. 35. The method according to claim 34, wherein the non-treatment period is from three weeks to six months.

Details for Patent 9,534,052

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2034-03-12
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2034-03-12
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	12/22/2014		2034-03-12
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	10/04/2017		2034-03-12
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	08/27/2021		2034-03-12