Claims for Patent: 8,840,888

Summary for Patent: 8,840,888

Title:	Dosage regimen for administering a CD19XCD3 bispecific antibody
Abstract:	Provided herein is a method for assessing the risk of potential adverse effects for a human patient mediated by the administration of a CD19.times.CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient, wherein a ratio of about 1:5 or lower is indicative for a risk of potential adverse effects for said patient.
Inventor(s):	Nagorsen; Dirk (Munich, DE), Kufer; Peter (Munich, DE), Zugmaier; Gerhard (Munich, DE), Baeuerle; Patrick (Munich, DE)
Assignee:	Micromet AG (Munich, DE)
Application Number:	13/504,665
Patent Claims:	1. A method for treating malignant CD19 positive lymphocytes in a human patient identified as having a peripheral blood B:T cell ratio of about 1:5 or lower before treatment to identify patients at risk of developing adverse effects, wherein said B:T cell ratio can be determined by the following steps: i) Determining the total B cell number in a peripheral blood sample of said human patient; ii) Determining the total T cell number in a peripheral blood sample of said human patient; iii) Calculating the ratio of the total B cell number of step i) and the total T cell number of step ii) in order to obtain a B:T cell ratio, said method comprising: (a) administering a first dose of a CD19.times.CD3 bispecific antibody for a first period of time to said human patient; and consecutively (b) administering a second dose of said antibody for a second period of time to said human patient; wherein said second dose exceeds said first dose, and wherein said CD19.times.CD3 bispecific antibody is MT103 (Blinatumomab). 2. The method of claim 1, wherein said method ameliorates and/or prevents an adverse effect mediated by the administration of a CD19.times.CD3 bispecific antibody to said human patient having a B:T cell ratio of about 1:5 or lower. 3. The method of claim 1, wherein said CD19 positive lymphocytes comprise malignant CD19 positive lymphoma or leukemia cells. 4. The method of claim 1, wherein the route of administration in step (a) and/or the route of administration in step (b) is intravenous. 5. The method of claim 2, wherein said adverse effect is characterized by a neurological reaction. 6. The method of claim 5, wherein said neurological reaction is one or more selected from the group consisting of: confusion, ataxia, disorientation, dysphasia, aphasia, speech impairment, cerebellar symptoms, tremor, apraxia, seizure, grand mal convulsion, palsy, and balance disorder. 7. The method of claim 1, wherein said second period of time exceeds said first period of time. 8. The method of claim 1, wherein said first period of time exceeds 3 days. 9. The method of claim 1, wherein said first period of time is between 3 days and 10 days. 10. The method of claim 1, wherein said second period of time exceeds 18 days. 11. The method of claim 1, wherein said second period of time is between 18 days and 81 days. 12. The method of claim 1, wherein said first period of time is between 3 days and 10 days, and said second period of time is between 18 days and 81 days. 13. The method of claim 12, wherein said first period of time is 7 days and said second period of time is 21 or 49 days. 14. The method of claim 1, wherein said first dose is between 1 and 15 .mu.g/m.sup.2/d. 15. The method of claim 1, wherein said second dose is between 15 and 60 .mu.g/m.sup.2. 16. The method of claim 1, further comprising administering after a first and second dose for a first and second period of time a third dose of said antibody for a third period of time. 17. The method of claim 16, wherein said first period of time exceeds 3 days. 18. The method of claim 16, wherein said first period of time is between 3 days and 10 days. 19. The method of claim 16, wherein said second period of time exceeds 3 days. 20. The method of claim 16, wherein said second period of time is between 3 days and 10 days. 21. The method of claim 16, wherein said third period of time exceeds 8 days. 22. The method of claim 16, wherein said third period of time is between 8 days and 78 days. 23. The method of claim 16, wherein said first period of time is between 3 days and 10 days, and said second period of time is between 3 days and 10 days, and said third period of time is between 8 days and 78 days. 24. The method of claim 23, wherein said first period of time is 7 days, said second period of time is 7 days and said third period of time is 14 or 42 days. 25. The method of claim 16, wherein said first dose is between 1 and 15 .mu.g/m.sup.2/d. 26. The method of claim 16, wherein said second dose is between 1 and 15 .mu.g/m2/d. 27. The method of claim 16, wherein said third dose is between 15 and 60 .mu.g/m.sup.2/d. 28. The method of claim 16, wherein the route of administration of the third dose is intravenous. 29. The method of claim 3, wherein the lymphoma is indolent or aggressive B cell non-Hodgkin lymphoma (B NHL), mantle cell lymphoma (MCL) or chronic lymphatic leukemia (CLL). 30. The method of claim 3, wherein the leukemia is B-lineage acute lymphoblastic leukemia (ALL). 31. The method of claim 16, wherein said antibody is administered at a first dose of 5 .mu.g/m.sup.2/d, followed by a second dose of 15 .mu.g/m.sup.2/d and consecutively followed by a third dose of 60 .mu.g/m.sup.2/d. 32. A method for ameliorating or preventing an adverse effect mediated by the administration of a CD19.times.CD3 bispecific antibody to a human patient having a B:T cell ratio of about 1:5 or lower, said method comprising: (a) determining the ratio of total B cells to total T cells in a peripheral blood sample from said human patient to identify patients at risk of developing an adverse effect; (b) identifying said human patient as having an increased risk of potential adverse effects when the ratio of B:T cells is about 1:5 or less before treatment; (c) administering a first dose of said antibody for a first period of time to said patient identified in (b), and consecutively; (d) administering a second dose of said antibody for a second period of time; wherein said second dose exceeds said first dose, and wherein said CD19.times.CD3 bispecific antibody is MT103 (Blinatumomab). 33. The method of claim 32, wherein said adverse effect is characterized by a neurological reaction. 34. The method of claim 33, wherein said neurological reaction is one or more selected from the group consisting of: confusion, ataxia, disorientation, dysphasia, aphasia, speech impairment, cerebellar symptoms, tremor, apraxia, seizure, grand mal convulsion, palsy, and balance disorder.

Details for Patent 8,840,888

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	BLINCYTO	blinatumomab	For Injection	125557	12/03/2014		2029-10-27

International Patent Family for US Patent 8,840,888

Country	Patent Number	Estimated Expiration
Australia	2010311559
Brazil	112012009778
Brazil	122019016866