Co-administration of a thrombolytic and an anti-CD18 antibody in stroke

• US 20020081294A1
• Filed: 12/20/2000
• Published: 06/27/2002
• Est. Priority Date: 01/23/1996
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Gross, Linda J., Thomas, G. Roger, Gross, Cordell E., Bednar, Martin M.
• Application Number:
  US09/811,384
• Publication Number:
  US 20020081294A1
• Time in Patent Office: Days
• US Class Current: 424/143.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/49 Urokinase; Tissue plasminogen activator
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/2821 against ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 16/2845 against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

A method for improving clinical outcome in focal ischemic stroke in a mammal by increasing cerebral blood flow and/or reducing infarct size is described which involves administering an effective amount of an ant-CD18 antibody to the mammal, in the absence of removal of the arterial obstruction.

Claims

1. A method for increasing cebral blood flow and/or reducing interfact size in focal ischemic stroke caused by obstruction of a main cerebral artery in a human mammal which comprise the step of co-administering effective amounts of tissue plasminogen actiator (tPA) and ati-CD18 antibody to mammal wherein neither the tPA nor the anti-CD18 antibody is administered to the mammal until about three to five hours after the onset of focal ischmic stroke.

2. The method of claim 1 that increase cerebral blood flow and reduces infarct cizo in the mammal.

3. The method of claim 1 wherein the anti-CD18 antibody is an antibody fragment.

4. The method of claim 3 wherein the anti-CD18 antibody fragment is a F(ab)₂.

5. The method of claim 1 wherein the anti-CD18 antibody is humanized.

6. The method of claim 1 wherein the anti-CD18 antibody is administered to the mammal by bolus dosage.

7. The method of claim 1 wherein the anti-CD18 antibody is administered inravenously.

8. The method of claim 1 wherein the anti-CD18 antibody is administered via cotinuos infusion.

9. The method of claim 1 wherein the anti-CD18 antibody and the tPA are simulteneously administered to the mammal.

10. The method of claim 1 wherein the anti-CD18 antibody is administered before the tPA is administered to the mammal.

11. The method of claim 1 wherein the anti-CD18 antibody is humanized H52 antibody comprising heavy chain sequence of SEQ ID NO:

10 and light chain sequence of SEQ ID NO;

11.

12. The method of claim 1 wherein the H52 antibody is a F(ab′

)₂.

13. The method of claim 1, wherein the anti-CD18 antibody binds to an extracellular domain of CD18 and inhibits or reduces the ability of a cell expressing CD18 to bind to endothelium.

14. The method of claim 1, wherein the anti-CD18 antibody binds CD18 with an affinity of 4 nm or less.

15. The method of claim 1, wherein the anti-CD18 antibody binds CD18 with an affinity of 3 nm or less.

16. The method of claim 1, wherein the anti-CD18 antibody binds CD18 with an affinity of 1 nm or less.

17. The method of claim 1, wherein the anti-CD18 antibody dissociates the CD11b/CD18 complex.

18. The method of claim 1, wherein the anti-CD18 antibody binds to the epitope bound by H52 antibody.