Claims for Patent: 10,336,821

Summary for Patent: 10,336,821

Title:	Method of treating stroke by administering a compound that inhibits VEGF-B signaling in combination with a thrombolytic agent
Abstract:	A method of reducing an effect of stroke in a subject, the method comprising administering to the subject a compound that inhibits VEGF-B signaling.
Inventor(s):	Eriksson; Ulf (Stockholm, SE), Nilsson; Ingrid (Stockholm, SE), Lawrence; Daniel (Ann Arbor, MI), Su; Enming Joe (Ann Arbor, MI)
Assignee:	CSL Limited (Parkville, Victoria, AU) B-Creative Sweden AB (Balsta, SE)
Application Number:	15/527,066
Patent Claims:	1. A method of reducing an effect of stroke in a subject, the method comprising administering to the subject a compound that inhibits VEGF-B signaling, wherein the compound that inhibits VEGF-B signaling is: an antibody or antigen binding fragment thereof that binds to or specifically binds to VEGF-B and neutralizes VEGF-B signaling, the antibody or antigen binding domain thereof comprising complementarity determining regions (CDRs) of a heavy chain variable region (V.sub.H) comprising a sequence set forth in SEQ ID NO: 3, and CDRs of a light chain variable region (V.sub.L), comprising a sequence set forth in SEQ ID NO: 4; and is administered after the stroke and in combination with a thrombolytic compound. 2. The method of claim 1, wherein the subject suffers from diabetes and/or obesity. 3. The method of claim 2, wherein the diabetes is type 2 diabetes. 4. The method of claim 1, wherein the subject has one or more of the following characteristics: (a) has already suffered from a stroke and/or a transient ischemic attack; (b) has a family history of stroke; (c) suffers from heart disease; (d) has high blood pressure; (e) has high plasma low density lipoprotein levels; (f) has metabolic syndrome (g) has a cardiac abnormality; and/or (h) has undergone cardiac surgery or hip replacement surgery. 5. The method of claim 1, wherein the compound that inhibits VEGF-B signaling is administered before the thrombolytic compound. 6. The method of claim 5, wherein administration of the compound that inhibits VEGF-B signaling extends the time in which the thrombolytic compound can safely be administered to the subject. 7. The method of claim 1, wherein the thrombolytic compound is administered more than two hours after onset of symptoms of a stroke. 8. The method of claim 1, wherein the subject has blood glucose levels greater than 400 mg/dL. 9. The method of claim 1, wherein the thrombolytic compound is selected from the group consisting of a tissue plasminogen activator, lanetoplase, reteplase, staphylokinase, streptokinase, anistreplase, desmoteplase or a urokinase. 10. The method of claim 1, wherein the compound that inhibits VEGF-B and/or the thrombolytic compound is administered in an amount sufficient to have one or more of the following effects: (a) reducing infarct size in the subject; (b) reducing the hemorrhage score as assessed by the intracerebral hemorrhage score in the subject; (c) reducing incidence of a hemorrhage in a subject; (d) reducing the likelihood of lethal hemorrhage in a subject; (e) reducing brain edema in the subject following stroke; and/or (f) reducing blood-brain-barrier breakdown or leakage in the subject following stroke. 11. The method of claim 1, wherein the stroke is an ischemic stroke. 12. The method of claim 1, wherein the compound that inhibits VEGF-B signaling comprises an Fv. 13. The method of claim 12, wherein the compound that inhibits VEGF-B signaling is selected from the group consisting of: (i) a single chain Fv fragment (scFv); (ii) a dimeric scFv (di-scFv); (iii) a diabody; (iv) a triabody; (v) a tetrabody; (vi) a Fab; (vii) a F(ab').sub.2; (viii) one of (i) to (vii) linked to a constant region of an antibody, Fc or a heavy chain constant domain (C.sub.H)2 and/or C.sub.H3; and (ix) an antibody. 14. The method of claim 13, wherein the antibody: (i) comprises a humanized variable region of the V.sub.H comprising a sequence set forth in SEQ ID NO: 3 and V.sub.L comprising a sequence set forth in SEQ ID NO: 4; or (ii) comprises a V.sub.H comprising a sequence set forth in SEQ ID NO: 5 and a V.sub.L comprising a sequence set forth in SEQ ID NO:6. 15. The method of claim 1, wherein the compound that inhibits VEGF-B signaling is an antibody or antigen binding fragment thereof comprising: (i) a V.sub.H comprising: (a) a CDR1 comprising a sequence set forth in SEQ ID NO: 21; (b) a CDR2 comprising a sequence set forth in SEQ ID NO: 22; and (c) a CDR3 comprising a sequence set forth in SEQ ID NO: 23; and (ii) a V.sub.L comprising: (a) a CDR1 comprising a sequence set forth in SEQ ID NO: 18; (b) a CDR2 comprising a sequence set forth in SEQ ID NO: 19; and (c) a CDR3 comprising a sequence set forth in SEQ ID NO: 20. 16. The method of claim 1, wherein the thrombolytic compound is administered between two and six hours after onset of symptoms of a stroke.

Details for Patent 10,336,821

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2034-11-17
Chiesi Usa, Inc.	RETAVASE	reteplase	For Injection	103786	10/30/1996		2034-11-17