Immunoglobulin chimeric monomer-dimer hybrids

1. A monomer-dimer hybrid immunoconjugate comprising a first polypeptide chain and a second polypeptide chain,

wherein said first chain comprises (i) a clotting factor and (ii) an immunoglobulin constant region or a portion thereof comprising a neonatal Fc Receptor binding site, and

said second chain comprises an immunoglobulin constant region or a portion thereof comprising a neonatal Fc Receptor binding site and does not comprise a biologically active molecule or an immunoglobulin variable domain, and

wherein said first chain and said second chain are linked.

2. The immunoconjugate of claim 1 , wherein said second chain consists of the immunoglobulin constant region or a portion thereof.

3. The immunoconjugate of claim 1 , wherein said immunoglobulin constant region or a portion thereof in said first chain is an Fc fragment.

4. The immunoconjugate of claim 3 , wherein said immunoglobulin constant region or a portion thereof in said second chain is an Fc fragment.

5. The immunoconjugate of claim 1 , wherein said immunoglobulin constant region or a portion thereof in said first chain and said immunoglobulin constant region or a portion thereof in said second chain are identical.

6. The immunoconjugate of claim 1 , wherein the clotting factor has a clotting activity.

7. The immunoconjugate of claim 6 , wherein the clotting factor activates one or more member of a coagulation cascade.

8. The immunoconjugate of claim 1 , wherein said immunoconjugate treats a bleeding disorder when administered to a subject in need thereof.

9. The immunoconjugate of claim 8 , wherein the bleeding disorder is hemophilia A or hemophilia B.

10. The immunoconjugate of claim 8 , wherein the bleeding disorder is an acute bleeding episode resulting from severe trauma.

11. The immunoconjugate of claim 8 , wherein said treatment is prophylactic.

12. The immunoconjugate of claim 1 , wherein the clotting factor and the immunoglobulin constant region or a portion thereof are connected by a linker.

13. The immunoconjugate of claim 12 , wherein said linker is selected from the group consisting of:

a. G n ;

b. (GA) n ;

c. (GGS) n ;

d. SEQ ID NO: 31;

e. SEQ ID NO: 34;

e. SEQ ID NO: 35;

f. SEQ ID NO: 36;

g. SEQ ID NO: 37;

h. SEQ ID NO: 38;

i. SEQ ID NO: 39;

j. SEQ ID NO: 40;

k. SEQ ID NO: 85; and

l. SEQ ID NO: 86;

where n is any integer between 1 and 10.

14. The immunoconjugate of claim 1 , wherein said clotting factor comprises one or more of Factor V, Factor VII, Factor VIIa, Factor VIII, Factor VIIIa, Factor IX, Factor IXa, Factor X, Factor Xa, Factor XI, Factor XII, Factor XIII, fibrinogen, prothrombin, von Willebrand factor, and a combination thereof.

15. The immunoconjugate of claim 4 , wherein said clotting factor is Factor VII or Factor VIIa.

16. The immunoconjugate of claim 4 , wherein said clotting factor is Factor VIII or Factor VIIIa.

17. The immunoconjugate of claim 4 , wherein said clotting factor is Factor IX or Factor IXa.

18. The immunoconjugate of claim 1 , wherein said first chain and said second chain are linked either covalently or non-covalently.

19. The immunoconjugate of claim 18 , wherein said first chain and said second chain are linked via a disulfide bond.

20. The immunoconjugate of claim 1 , wherein said clotting factor is a chimeric clotting factor, which has a clotting activity.

21. The immunoconjugate of claim 1 , wherein said immunoconjugate has higher maximum serum concentration (Cmax), when administered orally, compared to a homodimer comprising two polypeptide chains, each of which is identical to said first chain of the immunoconjugate.

22. A monomer-dimer hybrid immunoconjugate comprising a first polypeptide chain and a second polypeptide chain,

wherein said first chain comprises (i) Factor VIII or Factor VIIIa and (ii) an immunoglobulin constant region or a portion thereof comprising a neonatal Fc Receptor binding site, and

said second chain comprises an immunoglobulin constant region or a portion thereof comprising a neonatal Fc Receptor binding site and does not comprise a biologically active molecule or an immunoglobulin variable domain, and

wherein said first chain and said second chain are linked.

23. The immunoconjugate of claim 22 , wherein said second chain consists of the immunoglobulin constant region or a portion thereof.

24. A monomer-dimer hybrid immunoconjugate comprising a first polypeptide chain and a second polypeptide chain,

wherein said first chain comprises (i) Factor IX or Factor IXa and (ii) an immunoglobulin constant region or a portion thereof comprising a neonatal Fc Receptor binding site, and

said second chain comprises an immunoglobulin constant region or a portion thereof comprising a neonatal Fc Receptor binding site, and does not comprise a biologically active molecule or an immunoglobulin variable domain, and

wherein said first chain and said second chain are linked.

25. The immunoconjugate of claim 24 , wherein said second chain consists of the immunoglobulin constant region or a portion thereof.

26. A pharmaceutical composition comprising the immunoconjugate of claim 1 and a pharmaceutically acceptable carrier.

27. The composition of claim 26 , which is formulated for oral administration, buccal administration, sublingual administration, intravenous injection, subcutaneous injection, intramuscular injection, nasal administration, rectal administration vaginal administration, pulmonary administration, or inhalation.

28. The composition of claim 27 , further comprising at least one agent, which is capable of treating a disease or condition.

29. The composition of claim 28 , wherein said at least one agent is a protein comprising a clotting factor.

30. The composition of claim 29 , wherein said clotting factor is selected from the group consisting of Factor V, Factor VII, Factor VIIa, Factor VIII, Factor VIIIa, Factor IX, Factor IXa, Factor X, Factor Xa, Factor XI, Factor XII, Factor XIII, fibrinogen, prothrombin, von Willebrand factor, and a combination thereof.

31. The composition of claim 30 , wherein said at least one agent is a monomer-dimer hybrid immunoconjugate.

32. The composition of claim 30 , wherein said at least one agent is a dimer.

33. The immunoconjugate of claim 1 , wherein the second chain consists essentially of an Fc fragment.

34. The immunoconjugate of claim 33 , wherein the first chain consists essentially of (i) a clotting factor and (ii) an Fc fragment.

35. The immunoconjugate of claim 34 , wherein the clotting factor is FVII, FVIIa, FVIII, FVIIIa, FIX, or FIXa.

36. The immunoconjugate of claim 2 , wherein the first chain consists of (i) a clotting factor and (ii) an Fc fragment.

37. The immunoconjugate of claim 36 , wherein the clotting factor is FVIII or FVIIIa.

38. The immunoconjugate of claim 36 , wherein the clotting factor is FIX or FIXa.