IP Library › Granted Patent US 8,097,436

Granted Patent B2

US 8,097,436 · App. 12/938,180 · Granted Jan 17, 2012

Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof

Assignee: Roche GlycArt AG

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 8,097,436
App. No.: 12/938,180
Granted: Jan 17, 2012
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention relates to antigen binding molecules (ABMs). In particular embodiments, the present invention relates to recombinant monoclonal antibodies, including chimeric, primatized or humanized antibodies specific for human EGFR. In addition, the present invention relates to nucleic acid molecules encoding such ABMs, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the ABMs of the invention, and to methods of using these ABMs in treatment of disease. In addition, the present invention relates to ABMs with modified glycosylation having improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function.

Claims (237)

1. An isolated polynucleotide encoding a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises:

(a) a CDR1 selected from the group consisting of SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:123, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, and SEQ ID NO:125; and

(b) the CDR2 of SEQ ID NO:79; and

2. The polynucleotide of claim 1 , wherein said heavy chain variable domain comprises:

(a) a CDR1 selected from the group consisting of: SEQ ID NO:53, SEQ ID NO:59, and SEQ ID NO:65; and

(b) the CDR2 of SEQ ID NO:79; and

3. The polynucleotide of claim 2 , wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:53; and

(b) the CDR2 of SEQ ID NO:79; and

4. The polynucleotide of claim 1 , wherein said polynucleotide comprises:

(a) a sequence selected from the group consisting of SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:122, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, and SEQ ID NO:124; and

(b) SEQ ID NO:80; and

5. The polynucleotide of claim 4 , wherein said polynucleotide comprises:

(a) a sequence selected from the group consisting of: SEQ ID NO:54, SEQ ID NO:60, and SEQ ID NO:66; and

(b) SEQ ID NO:80; and

6. The polynucleotide of claim 5 , wherein said polynucleotide comprises:

(a) SEQ ID NO:54; and

(b) SEQ ID NO:80; and

7. The polynucleotide of claim 1 , wherein said polynucleotide further encodes a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO: 111 or SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

8. The polynucleotide of claim 7 , wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

9. The polynucleotide of claim 7 , wherein said polynucleotide comprises:

(a) SEQ ID NO:112 or SEQ ID NO:114; and

(b) SEQ ID NO:116 or SEQ ID NO:118; and

10. The polynucleotide of claim 9 , wherein said polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:118; and

11. An isolated polynucleotide encoding a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

12. The polynucleotide of claim 11 , wherein said polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:116 or SEQ ID NO:118; and

13. The polynucleotide of claim 12 , wherein said polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:118; and

14. The polynucleotide of claim 11 , wherein said polynucleotide further encodes a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises:

(a) a CDR1 selected from the group consisting of: SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:123, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, and SEQ ID NO:125; and

(b) a CDR2 selected from the group consisting of: SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:127, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, and SEQ ED NO:105; and

15. The polynucleotide of claim 14 , wherein said heavy chain variable domain comprises:

(a) a CDR1 selected from the group consisting of SEQ ID NO:53, SEQ ID NO:59, and SEQ ID NO:65; and

(b) a CDR2 selected from the group consisting of SEQ ID NO:79, SEQ ID NO:91, and SEQ ID NO:97; and

16. The polynucleotide of claim 15 , wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:53; and

(b) the CDR2 of SEQ ID NO:79; and

17. The polynucleotide of claim 15 , wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:59; and

(b) the CDR2 of SEQ ID NO:91; and

18. The polynucleotide of claim 15 , wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:65; and

(b) the CDR2 of SEQ ID NO:97; and

19. The polynucleotide of claim 14 , wherein said polynucleotide comprises:

(b) a sequence selected from the group consisting of SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:126, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, and SEQ ID NO:106; and

20. The polynucleotide of claim 19 , wherein said polynucleotide comprises:

(a) a sequence selected from the group consisting of: SEQ ID NO:54, SEQ ID NO:60. and SEQ ID NO:66; and

(b) a sequence selected from the group consisting of: SEQ ID NO:80, SEQ ID NO:92, and SEQ ID NO:98; and

21. The polynucleotide of claim 20 , wherein said polynucleotide comprises:

(a) SEQ ID NO:54; and

(b) SEQ ID NO:80; and

22. The polynucleotide of claim 20 , wherein said polynucleotide comprises:

(a) SEQ ID NO:60; and

(b) SEQ ID NO:92; and

23. The polynucleotide of claim 20 , wherein said polynucleotide comprises:

(a) SEQ ID NO:66; and

(b) SEQ ID NO:98; and

24. An isolated polynucleotide encoding a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises a sequence selected from the group consisting of: SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:15; SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21; SEQ ID NO:23; SEQ ID NO:25; SEQ ID NO:27; SEQ ID NO:29; SEQ ID NO:31; SEQ ID NO:33; SEQ ID NO:35; SEQ ID NO:37; SEQ ID NO:39; and SEQ ID NO:121.

25. The polynucleotide of claim 24 , wherein said heavy chain variable domain comprises SEQ ID NO: 15.

26. The polynucleotide of claim 24 , wherein said polynucleotide further encodes a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises a sequence selected from the group consisting of: SEQ ID NO:43; SEQ ID NO:45; SEQ ID NO:49; and SEQ ID NO:51.

27. The polynucleotide of claim 26 , wherein said light chain variable domain comprises SEQ ID NO:45.

28. An isolated polynucleotide encoding a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises a sequence selected from the group consisting of SEQ ID NO:45; SEQ ID NO:49; and SEQ ID NO:51.

29. The polynucleotide of claim 28 , where said polynucleotide further encodes a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:15; SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21; SEQ ID NO:23; SEQ ID NO:25; SEQ ID NO:27; SEQ ID NO:29; SEQ ID NO:31; SEQ ID NO:33; SEQ ID NO:35; SEQ ID NO:37; SEQ ID NO:39; and SEQ ID NO:121.

30. A vector comprising the polynucleotide of any of claim 1 , 11 , 24 or 28 .

31. The vector of claim 30 , wherein said vector is polycistronic.

32. The vector of claim 30 , wherein said vector is a replicative cloning vector.

33. The vector of claim 30 , wherein said vector is an expression vector.

34. A host cell comprising the polynucleotide of any of claim 1 , 11 , 24 , or 28 .

35. A host cell comprising a first polynucleotide and a second polynucleotide,

wherein said first polynucleotide is the polynucleotide of claim 1 , and

wherein said second polynucleotide encodes a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:111 or SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

36. The host cell of claim 35 ,

wherein said first polynucleotide encodes a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises:

(a) a CDR1 selected from the group consisting of: SEQ ID NO:53, SEQ ID NO:59, and SEQ ID NO:65; and

(b) the CDR2 of SEQ ID NO:79; and

wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:111 or SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

37. The host cell of claim 36 ,

wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:53; and

(b) the CDR2 of SEQ ID NO:79; and

wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

38. The host cell of claim 35 ,

wherein said first polynucleotide comprises:

(a) a sequence selected from the group consisting of: SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:122, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, and SEQ ID NO:124; and

(b) SEQ ID NO:80; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:112 or SEQ ID NO:114; and

(b) SEQ ID NO:116 or SEQ ID NO:118; and

39. The host cell of claim 38 ,

wherein said first polynucleotide comprises:

(a) a sequence selected from the group consisting of: SEQ ID NO:54, SEQ ID NO:60, and SEQ ID NO:66; and

(b) SEQ ID NO:80; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:112 or SEQ ID NO:114; and

(b) SEQ ID NO:116 or SEQ ID NO:118; and

40. The host cell of claim 39 ,

wherein said first polynucleotide comprises:

(a) SEQ ID NO:54; and

(b) SEQ ID NO:80; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:118; and

41. A host cell comprising a first polynucleotide and a second polynucleotide,

wherein said first polynucleotide encodes a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises:

wherein said second polynucleotide is the polynucleotide of claim 11 .

42. The host cell of claim 41 ,

wherein said heavy chain variable domain comprises:

(a) a CDR1 selected from the group consisting of SEQ ID NO:53, SEQ ID NO:59, and SEQ ID NO:65; and

(b) a CDR2 selected from the group consisting of SEQ ID NO:79, SEQ ID NO:91, and SEQ ID NO:97; and

wherein said second polynucleotide encodes a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

43. The host cell of claim 42 , wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:59; and

(b) the CDR2 of SEQ ID NO:91; and

wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

44. The host cell of claim 42 , wherein said heavy chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:65; and

(b) the CDR2 of SEQ ID NO:97; and

wherein said light chain variable domain comprises:

(a) the CDR1 of SEQ ID NO:113; and

(b) the CDR2 of SEQ ID NO:115; and

45. The host cell of claim 41 ,

wherein said first polynucleotide comprises:

(b) a sequence selected from the group consisting of: SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:126, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, and SEQ ID NO:106; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:116 or SEQ ID NO:118; and

46. The host cell of claim 45 ,

wherein said first polynucleotide comprises:

(a) a sequence selected from the group consisting of SEQ ID NO:54, SEQ ID NO:60, and SEQ ID NO:66; and

(b) a sequence selected from the group consisting of: SEQ ID NO:80, SEQ ID NO:92, and SEQ ID NO:98; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:116 or SEQ ID NO:118; and

47. The host cell of claim 46 ,

wherein said first polynucleotide comprises:

(a) SEQ ID NO:60; and

(b) SEQ ID NO:92; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:118; and

48. The host cell of claim 46 ,

wherein said first polynucleotide comprises:

(a) SEQ ID NO:66; and

(b) SEQ ID NO:98; and

wherein said second polynucleotide comprises:

(a) SEQ ID NO:114; and

(b) SEQ ID NO:118; and

49. A host cell comprising a first polynucleotide and a second polynucleotide,

wherein said first polynucleotide is the polynucleotide of claim 24 , and

wherein said second polynucleotide encodes a polypeptide comprising a light chain variable domain, wherein said light chain variable domain comprises a sequence selected from the group consisting of SEQ ID NO:43; SEQ ID NO:45; SEQ ID NO:49; and SEQ ID NO:51.

50. A host cell comprising a first polynucleotide and a second polynucleotide,

wherein said first polynucleotide encodes a polypeptide comprising a heavy chain variable domain, wherein said heavy chain variable domain comprises a sequence selected from the group consisting of: SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:15; SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21; SEQ ID NO:23; SEQ ID NO:25; SEQ ID NO:27; SEQ ID NO:29; SEQ ID NO:31; SEQ ID NO:33; SEQ ID NO:35; SEQ ID NO:37; SEQ ID NO:39; and SEQ ID NO:121, and

wherein said second polynucleotide is the polynucleotide of claim 28 .

51. The host cell of claim 49 or 50 ,

wherein said first polynucleotide encodes a polypeptide comprising a heavy chain variable domain comprising SEQ ID NO:15, and

wherein said second polynucleotide encodes a polypeptide comprising a light chain variable domain comprising SEQ ID NO:45.

52. The host cell of any of claim 35 , 41 , 49 , or 50 ,

wherein said host cell is engineered to express at least one nucleic acid encoding a polypeptide having β(1,4)-N-acetylglucosaminyltransferase III activity.

53. The host cell of claim 52 , wherein said host cell is further engineered to express at least one nucleic acid encoding a polypeptide having mannosidase II activity.

54. A method of producing an antigen binding molecule which is capable of competing with the rat ICR62 monoclonal antibody for binding to human EGFR, said method comprising:

(a) culturing the host cell of any of claim 35 , 41 , 49 , or 50 , in a medium under conditions allowing the expression of said first polynucleotide and said second polynucleotide, and

(b) recovering said antigen binding molecule.

55. The polynucleotide of claim 28 , wherein said light chain variable domain comprises SEQ ID NO:45.

Assignments (3)

RELEASE OF SECURITY INTEREST Recorded Jun 12, 2026

From: COCOON SA LLC

To: APCINTEX LIMITED; JANPIX LIMITED; CAPELLA BIOSCIENCE LTD; LOCKBODY THERAPEUTICS LTD; ULTRAHUMAN TWO LIMITED; ULTRAHUMAN FOUR LIMITED; MORPHOGEN-IX LIMITED; OREXIA THERAPEUTICS LIMITED; CARDIOKINE BIOPHARMA LLC; CENTESSA BIOSCIENCES, INC; PEARLRIVER BIO GMBH; Z FACTOR LIMITED

Reel/Frame 075737/0001 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 19, 2011

From: UMANA, PABLO; MOSSNER, EKKEHARD

To: GLYCART BIOTECHNOLOGY AG

Reel/Frame 026929/0586 →

CHANGE OF NAME Recorded Sep 9, 2011

From: GLYCART BIOTECHNOLOGY AG

To: ROCHE GLYCART AG

Reel/Frame 026883/0831 →

Continuity (4)

Division 11889981 · Aug 17, 2007

Division 11348526 · Feb 7, 2006

Provisional Application 60650115 · Feb 7, 2005

Related Publication 20110111461A1 · May 12, 2011