BISPECIFIC ANTIBODIES

• US 20090068181A1
• Filed: 09/09/2008
• Published: 03/12/2009
• Est. Priority Date: 06/28/2004
• Status: Abandoned Application

• Current Assignee: Transtarget, Inc.
• Original Assignee: Transtarget, Inc.
• Inventors: LEE, Randall J., Lum, Lawrence G., Larrick, James
• Application Number:
  US12/207,285
• Publication Number:
  US 20090068181A1
• Time in Patent Office: Days
• US Class Current: 424/133.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/289 against CD45
• CPC Class Codes: C07K 2317/31 multispecific

Abstract

The present invention provides compositions and methods for targeting stem cells to injured cardiac tissue.

Claims

1. A composition, the composition comprising a polypeptide comprising a cardiac antigen-specific binding component and a stem cell antigen-specific binding component,

wherein the cardiac antigen-specific binding component comprises a polypeptide that specifically binds to a cardiac antigen available for binding to the cardiac antigen-specific binding component, wherein the cardiac antigen is selected from the group consisting of:

myosin light chain and troponin I; and

wherein the stem cell antigen-specific component comprises a polypeptide that specifically binds to an antigen expressed on the surface of a stem cell.

2. The composition of claim 1, wherein the cardiac antigen-specific binding component and the stem cell antigen-specific binding component are chemically conjugated.

3. The composition of claim 1, further comprising the stem cell bound to the stem cell antigen-specific binding component.

4. The composition of claim 3, wherein the stem cell is selected from the group consisting of:

a peripheral blood stem cell (PBSC), a stem cell isolated from bone marrow;

a stem cell isolated from adipose tissue;

a mesenchymal stem cell, an embryonic stem cell, an umbilical cord blood stem cell, a CD34⁺ cell, a CD34⁻

cell, a CD45⁺ cell, and combinations thereof.

5. The composition of claim 4, wherein the stem cell is a PBSC.

6. The composition of claim 1, wherein the cardiac antigen-specific binding component and the stem cell antigen-specific binding component are each antibodies.

7. The composition of claim 6, wherein the antibodies are (Fab)′

₂ fragments.

8. The composition of claim 6, wherein the antibodies are scFv.

9. The composition of claim 6, wherein the antibodies are humanized.

10. The composition of claim 6, wherein the stem cell antigen-specific binding component is an antibody that specifically binds to a member selected from the group consisting of:

CD9, CD29, CD34, CD44, CD45, CD49e, CD54, CD71, CD90, CD105, CD106, CD120a, CD124, CD166, Sca-1, SH2, SH3, and HLA Class I.

11. The composition of claim 10, wherein the stem cell antigen-specific binding component is an antibody that specifically binds to CD45.

12. A method for targeting stem cells to injured cardiac tissue, the method comprising:

administering a composition to a subject, said composition comprising a polypeptide comprising a cardiac antigen-specific binding component and a stem cell antigen-specific binding component,

wherein the cardiac antigen-specific binding component comprises a polypeptide that specifically binds to a cardiac antigen available for binding to the first component, wherein the cardiac specific antigen is selected from the group consisting of;

myosin light chain and troponin I;

wherein the stem cell antigen-specific binding component comprises a polypeptide that specifically binds to an antigen expressed on the surface of a stem cell; and

wherein the polypeptide is bound to the stem cell.

13. The method of claim 12, wherein the first binding component and the stem cell antigen-specific binding component are chemically conjugated.

14. The method of claim 12, wherein the stem cell is a peripheral blood stem cell.

15. The method of claim 12, wherein the cardiac antigen-specific binding component and the stem cell antigen-specific binding component are each antibodies.

16. The method of claim 15, wherein the antibodies are (Fab)′

2 fragments.

17. The method of claim 15, wherein the antibodies are scFv.

18. The method of claim 15, wherein the antibodies are humanized.

19. The method of claim 15, wherein the second binding component is an antibody that specifically binds to CD45.

20. The method of claim 12, wherein the subject is a mammal.

21. The method of claim 20, wherein the mammal is a human.

22. Use, in the manufacture of a medicament for targeting stem cells to injured cardiac tissue of a polypeptide comprising a cardiac antigen-specific binding component and a stem cell antigen-specific binding component,

wherein the cardiac antigen-specific binding component comprises a polypeptide that specifically binds to a cardiac-specific antigen available for binding to the first component, wherein the cardiac specific antigen is selected from the group consisting of:

myosin light chain and troponin I; and

wherein the stem cell antigen-specific binding component comprises a polypeptide that specifically binds to an antigen expressed on the surface of a stem cell.

23. The use of claim 22, wherein the polypeptide is bound to the stem cell.

24. The use of claim 23, wherein the stem cell is selected from the group consisting of:

a peripheral blood stem cell (PBSC), a stem cell isolated from bone marrow;

a stem cell isolated from adipose tissue;

a mesenchymal stem cell, an embryonic stem cell, an umbilical cord blood stem cell, a CD34⁺ cell, a CD34⁻

cell, a CD45⁺ cell, and combinations thereof.

25. The use of claim 23, wherein the antigen expressed on the surface of a stem cell is selected from the group consisting of:

CD9, CD29, CD34, CD44, CD45, CD49e, CD54, CD71, CD90, CD105, CD106, CD120a, CD124, CD166, Sca-1, SH2, SH3, and HLA Class I.