IP Library › Granted Patent US 8,629,245
Granted Patent B2
US 8,629,245 · App. 12/112,971 · Granted Jan 14, 2014

Immunoglobulin Fc libraries

Inventors: George Georgiou (Austin, TX); Sang Taek Jung (Austin, TX)
Assignee: Research Development Foundation
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,629,245
App. No.
12/112,971
Granted
Jan 14, 2014
Kind
B2
Abstract

Methods and composition for the screening and isolation of aglycosylated antibody Fc domain polypeptides. For example, in certain aspects methods for identifying aglycosylated Fc domains that bind to Fc receptors or preferentially bind to particular Fc receptors are described. Furthermore, the invention provides aglycosylated Fc domains that bind to Fc receptors with high affinity. Enhanced methods and media for prokaryotic based interaction screening are also provided.

Claims (44)

1. A polypeptide comprising an aglycosylated variant human IgG Fc domain capable of binding an FcR polypeptide, wherein the variant Fc domain comprises an amino acid substitution of P331L, E382V, M428I or M428L, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat, and further wherein the Fc domain comprises a substitution selected from the group consisting of a) E382V and M428I; b) E382V; c) N361D, E382V and M428I; d) N361D, F372L, E382V and M428I; e) H310Y, K322R, T350A, E382V, S426T and S442P; f) C229R, E382V and M428I; g) W313R and M428I; h) E382T, N384D and M428I; i) E380R, E382M and N384E; j) N361S, E382V and M428I; k) E382V, M428I and Y436A; l) P238S, E382V, S426V, M428L and E430H; m) E380D, E382V, N384R, S426V, M428L and E430D; n) E382V, S426I, M428L and E430S; o) H224R, E382V, S426T, M428S and E430P; p) S239L, 1253T, Q347L, E382V; q) E382V, G402D and M428I; and r) E382V, P331L and M428I.

2. The polypeptide of claim 1 , wherein the aglycosylated antibody Fc domain is Fc11 (SEQ ID NO: 2), Fc5 (SEQ ID NO: 3), Fc12 (SEQ ID NO: 4), Fc 20 (SEQ ID NO: 5), Fc49 (SEQ ID NO: 6), Fc23 (SEQ ID NO: 7), Fc104 (SEQ ID NO: 65), Fc106 (SEQ ID NO: 66), Fc110 (SEQ ID NO: 67), Fc114 (SEQ ID NO: 68), Fc117 (SEQ ID NO: 69), Fc143 (SEQ ID NO: 70), Fc149 (SEQ ID NO: 71), Fc151 (SEQ ID NO: 72), Fc152 (SEQ ID NO: 73), Fc331 (SEQ ID NO: 79), Fc402 (SEQ ID NO: 81) or Fc403 (SEQ ID NO: 82).

3. The polypeptide of claim 2 , wherein the aglycosylated antibody Fc domain is Fc5 (SEQ ID NO: 3).

4. The polypeptide of claim 3 , further comprising an Ig variable domain.

5. The polypeptide of claim 4 , further defined as a full length antibody.

6. The polypeptide of claim 1 , further comprising an Ig variable domain.

7. The polypeptide of claim 6 , further defined as a full length antibody.

8. The polypeptide of claim 1 , wherein the Fc domain binds to FcγRIa with an equilibrium dissociation constant of about 10 −6 M to about 10 −9 M under physiological conditions.

9. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E382V and M428I.

10. The polypeptide of claim 9 , wherein the wherein the aglycosylated antibody Fc domain is Fc5 (SEQ ID NO:3).

11. The polypeptide of claim 1 , wherein the Fc domain comprises the substitution E382V.

12. The polypeptide of claim 11 , wherein the wherein the aglycosylated antibody Fc domain is Fc11 (SEQ ID NO:2).

13. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions N361D, E382V and M428I.

14. The polypeptide of claim 13 , wherein the wherein the aglycosylated antibody Fc domain is Fc12 (SEQ ID NO: 4).

15. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions N361D, F372L, E382V and M428I.

16. The polypeptide of claim 15 , wherein the wherein the aglycosylated antibody Fc domain is Fc 20 (SEQ ID NO: 5).

17. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions H310Y, K322R, T350A, E382V, S426T and S442P.

18. The polypeptide of claim 17 , wherein the wherein the aglycosylated antibody Fc domain is Fc23 (SEQ ID NO: 7).

19. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions C229R, E382V and M428I.

20. The polypeptide of claim 19 , wherein the wherein the aglycosylated antibody Fc domain is Fc49 (SEQ ID NO: 6).

21. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions W313R and M428I.

22. The polypeptide of claim 21 , wherein the wherein the aglycosylated antibody Fc domain is Fc104 (SEQ ID NO: 65).

23. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E382T, N384D and M428I.

24. The polypeptide of claim 23 , wherein the wherein the aglycosylated antibody Fc domain is Fc106 (SEQ ID NO: 66).

25. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E380R, E382M and N384E.

26. The polypeptide of claim 25 , wherein the wherein the aglycosylated antibody Fc domain is Fc110 (SEQ ID NO: 67).

27. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions N361S, E382V and M428I.

28. The polypeptide of claim 27 , wherein the wherein the aglycosylated antibody Fc domain is Fc114 (SEQ ID NO: 68).

29. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E382V, M428I and Y436A.

30. The polypeptide of claim 29 , wherein the wherein the aglycosylated antibody Fc domain is Fc117 (SEQ ID NO: 69).

31. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions P238S, E382V, S426V, M428L and E430H.

32. The polypeptide of claim 31 , wherein the wherein the aglycosylated antibody Fc domain is Fc143 (SEQ ID NO: 70).

33. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E380D, E382V, N384R, S426V, M428L and E430D.

34. The polypeptide of claim 33 , wherein the wherein the aglycosylated antibody Fc domain is Fc149 (SEQ ID NO: 71).

35. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E382V, S426I, M428L and E430S.

36. The polypeptide of claim 35 , wherein the wherein the aglycosylated antibody Fc domain is Fc151 (SEQ ID NO: 72).

37. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions H224R, E382V, S426T, M428S and E430P.

38. The polypeptide of claim 37 , wherein the wherein the aglycosylated antibody Fc domain is Fc152 (SEQ ID NO: 73).

39. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions S239L, 1253T, Q347L, E382V.

40. The polypeptide of claim 39 , wherein the wherein the aglycosylated antibody Fc domain is Fc331 (SEQ ID NO: 79).

41. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E382V, G402D and M428I.

42. The polypeptide of claim 41 , wherein the wherein the aglycosylated antibody Fc domain is Fc402 (SEQ ID NO: 81).

43. The polypeptide of claim 1 , wherein the Fc domain comprises the substitutions E382V, P331L and M428I.

44. The polypeptide of claim 43 , wherein the wherein the aglycosylated antibody Fc domain is Fc403 (SEQ ID NO: 82).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2008
From: GEORGIOU, GEORGE; JUNG, SANG TAEK
To: RESEARCH DEVELOPMENT FOUNDATION
Reel/Frame 021367/0194 →
Continuity (3)
Provisional Application 60915183 · May 1, 2007
Provisional Application 60982652 · Oct 25, 2007
Related Publication 20090136936A1 · May 28, 2009