IP Library › Granted Patent US 50,880
Granted Patent E1
US 50,880 · App. 17/816,698 · Granted May 5, 2026

Anti-human OX40L antibodies and methods of treatment

Inventors: Jamie Campbell (Cambridge, GB); Steve Holmes (Cambridge, GB); Ian Kirby (Cambridge, GB); Miha Kosmac (Cambridge, GB)
Assignee: Kymab Limited
C07K16/2875A61K39/3955A61K2039/505C07K2317/33C07K2317/76
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 50,880
App. No.
17/816,698
Granted
May 5, 2026
Kind
E1
Abstract

The present invention relates to anti-human OX40L antibodies, new medical uses and methods.

Claims (63)

1 . An antibody or a fragment thereof that specifically binds to hOX40L and competes for binding to said hOX40L with the antibody 02D10 which comprises a heavy chain amino acid sequence of SEQ ID No:62 and a light chain amino acid sequence of SEQ ID No:64, the antibody or fragment thereof comprising a VH domain which comprises the HCDR3 sequence of SEQ ID NO:40 or 46.

2 . The antibody or fragment thereof according to claim 1 , wherein the VH domain comprises the HCDR1 sequence of SEQ ID NO:36 or 42.

3 . The antibody or fragment thereof according to claim 1 , wherein the VH domain comprises the HCDR1 sequence of SEQ ID NO:36 or 42, and the VH domain comprises the HCDR2 sequence of SEQ ID NO:38 or 44.

4 . The antibody or fragment thereof according to claim 1 , wherein the VH domain comprises the HCDR1 sequence of SEQ ID NO:36 or 42, and the VH domain comprises the HCDR2 sequence of SEQ ID NO:38 or 44, and wherein the antibody or fragment thereof further comprises a VL domain which comprises the LCDR1 sequence of SEQ ID NO:54 or 60.

5 . The antibody or fragment thereof according to claim 1 , wherein the VH domain comprises the HCDR1 sequence of SEQ ID NO:36 or 42, and the VH domain comprises the HCDR2 sequence of SEQ ID NO:38 or 44, and wherein the antibody or fragment thereof further comprises a VL domain comprising the LCDR1 sequence of SEQ ID NO:54 or 60, and the VL domain comprising the LCDR2 sequence of SEQ ID NO:52 or 58.

6 . The antibody or fragment thereof according to claim 1 , wherein the VH domain comprises the HCDR1 sequence of SEQ ID NO:36 or 42, and the VH domain comprises the HCDR2 sequence of SEQ ID NO:38 or 44, and wherein the antibody or fragment thereof further comprises a VL domain comprising the LCDR1 sequence of SEQ ID NO:54 or 60, the VL domain comprising the LCDR2 sequence of SEQ ID NO:52 or 58, and the VL domain comprising the LCDR3 sequence of SEQ ID NO:54 or 60.

7 . The antibody or fragment thereof according to claim 6 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO:34.

8 . The antibody or fragment thereof according to claim 6 comprising a first and a second copy of the VH domain.

9 . The antibody or fragment thereof according to claim 6 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:48.

10 . The antibody or fragment thereof according to claim 6 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:48 and the VH domain comprises the amino acid sequence of SEQ ID NO:34.

11 . The antibody or fragment thereof according to claim 6 comprising a first and a second copy of the VL domain.

12 . The antibody or fragment thereof according to claim 6 comprising a kappa light chain.

13 . The antibody or fragment thereof according to claim 6 comprising a constant region.

14 . The antibody or fragment thereof according to claim 10 comprising a IgG4-PE constant region of SEQ ID NO:128.

15 . A composition comprising an antibody or a fragment thereof that specifically binds to hOX40L and competes for binding to said hOX40L with the antibody 02D10 which comprises a heavy chain amino acid sequence of SEQ ID No:62 and a light chain amino acid sequence of SEQ ID No:64, and a pharmaceutically acceptable excipient, diluent, or carrier; wherein the antibody or fragment thereof comprises a VH domain comprising the HCDR3 sequence of SEQ ID NO:40 or 46.

16 . The composition according to claim 15 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:48 and the VH domain comprises the amino acid sequence of SEQ ID NO:34.

17 . The composition according to claim 15 , further comprising another agent that is a therapeutic or prophylactic agent for graft versus host disease (GvHD) or transplant rejection.

18 . The composition according to claim 15 contained in a kit with a label or instructions for use to treat and/or prevent graft versus host disease (GvHD) or transplant rejection.

19 . The composition according to claim 18 , wherein the kit comprises a marketing authorisation number.

20 . The composition according to claim 18 , wherein the kit further comprises an IV or injection device that comprises the antibody or fragment thereof.

21 . A method of treating or preventing graft versus host disease (GvHD) or transplant rejection in a human in need thereof, the method comprising administering to said human a therapeutically effective amount of an antibody or fragment thereof as defined in claim 6 , wherein the graft versus host disease (GvHD) or transplant rejection is thereby treated or prevented.

22 . The method according to claim 21 , wherein the antibody or fragment thereof is administered prophylactically.

23 . The method according to claim 21 , wherein the antibody or fragment thereof is administered prophylactically and wherein the antibody or fragment thereof enables greater than 80% stem cell donor chimerism by day 12 in a Rhesus macaque model of haploidentical hematopoietic stem cell transplantation.

24 . The method according to claim 21 , wherein the antibody or fragment thereof is administered prophylactically and wherein the antibody or fragment thereof maintains a naïve population of CD4+ T cells of >20% of total CD4+ T cell population at day 12 in a Rhesus macaque model of haploidentical hematopoietic stem cell transplantation.

25 . The method according to claim 21 , wherein the antibody or fragment thereof is administered prophylactically and further comprising administering to the human a further therapeutic or preventative agent for graft versus host disease or transplant rejection.

26 . The antibody or fragment thereof according to claim 13 , wherein the constant region comprises an IgG4-PE constant region, wherein the IgG4-PE constant region comprises a Leu235Glu mutation and a Ser228Pro mutation relative to the wild-type IgG4 constant region.

27 . The composition of claim 15 , wherein the VH domain of the antibody or fragment thereof comprises the HCDR1 sequence of SEQ ID NO:36 or 42, and the HCDR2 sequence of SEQ ID NO:38 or 44, and wherein the antibody or fragment thereof comprises a VL domain which comprises the LCDR1 sequence of SEQ ID NO:54 or 6050 or 56, the LCDR2 sequence of Ala-Ala-Ser or SEQ ID NO:52 or58, and a LCDR3 sequence of SEQ ID NO:54 or 60.

28. An antibody that specifically binds to hOX40L and comprises

a VH domain comprising the HCDR1 sequence of SEQ ID NO:36 or 42, the HCDR2 sequence of SEQ ID NO: 38 or 44, and the HCDR3 sequence of SEQ ID NO:40 or 46, and

a VL domain comprising the LCDR1 sequence of SEQ ID NO: 50 or 56, the LCDR2 sequence of Ala-Ala-Ser or 58, and the LCDR3 sequence of SEQ ID NO:54 or 60.

29. The antibody of claim 28 , further comprising a human heavy chain constant region and a human light chain constant region.

30. An antibody that specifically binds to hOX40L and comprises a VH domain comprising SEQ ID NO:34 and a VL domain comprising SEQ ID NO:48.

31. An antibody that specifically binds to hOX40L and comprises two copies of a heavy chain comprising SEQ ID NO:62 and two copies of a light chain comprising SEQ ID NO:64.

32. An antibody that specifically binds to hOX40L and consists of two copies of a heavy chain consisting of SEQ ID NO:62 and two copies of a light chain consisting of SEQ ID NO:64.

33. The composition of claim 15 , wherein the VH domain comprises an amino acid sequence comprising SEQ ID NO:36, SEQ ID NO:38, and SEQ ID NO:40; and the VL domain comprises an amino acid sequence comprising SEQ ID NO:50, Ala-Ala-Ser, and SEQ ID NO:54.

34. The composition of claim 15 , wherein the VH domain comprises an amino acid sequence comprising SEQ ID NO:42, SEQ ID NO:44, and SEQ ID NO:46; and the VL domain comprises an amino acid sequence comprising SEQ ID NO:56, SEQ ID NO:58, and SEQ ID NO:60.

35. The antibody of claim 28 , wherein the VH domain comprises an amino acid sequence comprising SEQ ID NO:36, SEQ ID NO:38, and SEQ ID NO:40; and the VL domain comprises an amino acid sequence comprising SEQ ID NO:50, Ala-Ala-Ser, and SEQ ID NO:54.

36. The antibody of claim 28 , wherein the VH domain comprises an amino acid sequence comprising SEQ ID NO:42, SEQ ID NO:44, and SEQ ID NO:46; and the VL domain comprises an amino acid sequence comprising SEQ ID NO:56, SEQ ID NO:58, and SEQ ID NO:60.

37. A composition comprising the antibody of claim 28 and a pharmaceutically acceptable excipient, diluent, or carrier.

38. A composition comprising the antibody of claim 29 and a pharmaceutically acceptable excipient, diluent, or carrier.

39. A composition comprising the antibody of claim 30 and a pharmaceutically acceptable excipient, diluent, or carrier.

40. A composition comprising the antibody of claim 31 and a pharmaceutically acceptable excipient, diluent, or carrier.

41. A composition comprising the antibody of claim 32 and a pharmaceutically acceptable excipient, diluent, or carrier.

42. A composition comprising the antibody of claim 35 and a pharmaceutically acceptable excipient, diluent, or carrier.

43. A composition comprising the antibody of claim 36 and a pharmaceutically acceptable excipient, diluent, or carrier.

44. An antibody or a fragment thereof that specifically binds to hOX40L and competes for binding to said hOX40L with the antibody 02D10, which comprises a heavy chain amino acid sequence of SEQ ID NO:62 and a light chain amino acid sequence of SEQ ID NO:64, the antibody or fragment thereof comprising

(i) a VH domain which comprises the HCDR1 sequence of SEQ ID NO:36 or 42, the HCDR2 sequence of SEQ ID NO:38 or 44, and the HCDR3 sequence of SEQ ID NO:40 or 46; and

(ii) a VL domain that comprises the LCDR1 sequence of SEQ ID NO:50 or 56, the LCDR2 sequence of Ala-Ala-Ser or SEQ ID NO:58, and the LCDR3 sequence of SEQ ID NO:54 or 60.

45. The antibody or fragment thereof according to claim 1 , wherein the VH domain further comprises the HCDR1 sequence of SEQ ID NO:36 or 42 and the HCDR2 sequence of SEQ ID NO:38 or 44, and wherein the antibody or fragment thereof further comprises a VL domain that comprises the LCDR1 sequence of SEQ ID NO:50 or 56.

46. The antibody or fragment thereof according to claim 1 , wherein the VH domain further comprises the HCDR1 sequence of SEQ ID NO:36 or 42 and the HCDR2 sequence of SEQ ID NO:38 or 44, and wherein the antibody or fragment thereof further comprises a VL domain comprising the LCDR1 sequence of SEQ ID NO:50 or 56 and the LCDR2 sequence of Ala-Ala-Ser or SEQ ID NO:58.

47. The antibody or fragment thereof according to claim 44 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO:34.

48. The antibody or fragment thereof according to claim 44 , comprising a first and a second copy of the VH domain.

49. The antibody or fragment thereof according to claim 44 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:48.

50. The antibody or fragment thereof according to claim 44 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:48 and the VH domain comprises the amino acid sequence of SEQ ID NO:34.

51. The antibody or fragment thereof according to claim 44 , comprising a first and a second copy of the VL domain.

52. The antibody or fragment thereof according to claim 44 , comprising a kappa light chain.

53. The antibody or fragment thereof according to claim 44 , comprising a constant region.

54. The antibody or fragment thereof according to claim 50 , comprising a IgG4-PE constant region of SEQ ID NO: 128.

55. The antibody or fragment thereof according to claim 53 , wherein the constant region comprises an IgG4-PE constant region, wherein the IgG4-PE constant region comprises a Leu235Glu mutation and a Ser228Pro mutation relative to the wild-type human IgG4 constant region of SEQ ID NO: 122.

56. The antibody or fragment thereof of claim 44 , wherein the VH domain comprises an amino acid sequence comprising SEQ ID NO:36: SEQ ID NO:38: and SEQ ID NO:40; and the VL domain comprises an amino acid sequence comprising SEQ ID NO:50, Ala-Ala-Ser, and SEQ ID NO:54.

57. The antibody or fragment thereof of claim 44 , wherein the VH domain comprises an amino acid sequence comprising SEQ ID NO:42, SEQ ID NO:44, and SEQ ID NO:46; and the VL domain comprises an amino acid sequence comprising SEQ ID NO:56, SEQ ID NO:58, and SEQ ID NO:60.

58. A composition comprising the antibody or fragment thereof of claim 56 and a pharmaceutically acceptable excipient, diluent, or carrier.

59. A composition comprising the antibody or fragment thereof of claim 57 and a pharmaceutically acceptable excipient, diluent, or carrier.

Continuity (1)
Reissue 14700896 · Apr 30, 2015
References Cited (400)
US 4663281A · Gillies et al. · 1987 [cited by applicant]
US 4741900A · Alvarez et al. · 1988 [cited by applicant]
US 4816397A · Boss et al. · 1989 [cited by applicant]
US 5219996A · Bodmer et al. · 1993 [cited by applicant]
US 5223409A · Ladner et al. · 1993 [cited by applicant]
US 5314995A · Fell, Jr. et al. · 1994 [cited by applicant]
US 5403484A · Ladner et al. · 1995 [cited by applicant]
US 5427908A · Dower et al. · 1995 [cited by applicant]
US 5516637A · Huang et al. · 1996 [cited by applicant]
US 5545806A · Lonberg et al. · 1996 [cited by applicant]
US 5545807A · Surani et al. · 1996 [cited by applicant]
US 5569825A · Lonberg et al. · 1996 [cited by applicant]
US 5571698A · Ladner et al. · 1996 [cited by applicant]
US 5580717A · Dower et al. · 1996 [cited by applicant]
US 5585089A · Queen et al. · 1996 [cited by applicant]
US 5625126A · Lonberg et al. · 1997 [cited by applicant]
US 5633425A · Lonberg et al. · 1997 [cited by applicant]
US 5645835A · Fell, Jr. et al. · 1997 [cited by applicant]
US 5658727A · Barbas et al. · 1997 [cited by applicant]
US 5661016A · Lonberg et al. · 1997 [cited by applicant]
US 5677425A · Bodmer et al. · 1997 [cited by applicant]
US 5698426A · Huse · 1997 [cited by applicant]
US 5712380A · Kendall et al. · 1998 [cited by applicant]
US 5733743A · Johnson et al. · 1998 [cited by applicant]
US 5750753A · Kimae et al. · 1998 [cited by applicant]
US 5766886A · Studnicka et al. · 1998 [cited by applicant]
US 5770429A · Lonberg et al. · 1998 [cited by applicant]
US 5780225A · Wigler et al. · 1998 [cited by applicant]
US 5821047A · Garrard et al. · 1998 [cited by applicant]
US 5869046A · Presta et al. · 1999 [cited by applicant]
US 5869619A · Studnicka · 1999 [cited by applicant]
US 5969108A · McCafferty et al. · 1999 [cited by applicant]
US 6011003A · Charnock-Jones et al. · 2000 [cited by applicant]
US 6028176A · Greve et al. · 2000 [cited by applicant]
US 6100071A · Davis-Smyth et al. · 2000 [cited by applicant]
US 6121022A · Presta et al. · 2000 [cited by applicant]
US 6331415B1 · Cabilly et al. · 2001 [cited by applicant]
US 6407088B1 · Dong et al. · 2002 [cited by applicant]
US 6528055B2 · Godfrey et al. · 2003 [cited by applicant]
US 6528623B2 · Godfrey et al. · 2003 [cited by applicant]
US 6548507B1 · Bountra et al. · 2003 [cited by applicant]
US 6599906B1 · Ku et al. · 2003 [cited by applicant]
US 6803039B2 · Tsuji et al. · 2004 [cited by applicant]
US 6875432B2 · Liu et al. · 2005 [cited by applicant]
US 6897294B2 · Davis-Smyth et al. · 2005 [cited by applicant]
US 7029895B2 · Glucksmann et al. · 2006 [cited by applicant]
US 7030225B1 · Tamatani et al. · 2006 [cited by applicant]
US 7045615B2 · Tamatani et al. · 2006 [cited by applicant]
US 7056509B2 · Thorpe et al. · 2006 [cited by applicant]
US 7098184B2 · Godfrey et al. · 2006 [cited by applicant]
US 7125551B2 · Kroczek · 2006 [cited by applicant]
US 7129338B1 · Otal et al. · 2006 [cited by applicant]
US 7132099B2 · Kroczek · 2006 [cited by applicant]
US 7166283B2 · Tsuji et al. · 2007 [cited by applicant]
US 7196175B2 · Tamatani et al. · 2007 [cited by applicant]
US 7226909B2 · Tamatani et al. · 2007 [cited by applicant]
US 7259247B1 · Kroczek · 2007 [cited by applicant]
US 7261893B2 · Veldman et al. · 2007 [cited by applicant]
US 7279560B2 · Tamatani et al. · 2007 [cited by applicant]
US 7291331B1 · Croft et al. · 2007 [cited by applicant]
US 7300754B2 · Abi Fadel et al. · 2007 [cited by applicant]
US 7304033B2 · Larsen et al. · 2007 [cited by applicant]
US 7306800B2 · Kroczek · 2007 [cited by applicant]
US 7368531B2 · Rosen et al. · 2008 [cited by applicant]
US 7411051B2 · Rosen et al. · 2008 [cited by applicant]
US 7438905B2 · Suzuki et al. · 2008 [cited by applicant]
US 7456187B2 · Ford et al. · 2008 [cited by applicant]
US 7456264B2 · Keler et al. · 2008 [cited by applicant]
US 7465445B2 · Tezuka et al. · 2008 [cited by applicant]
US 7482147B2 · Glucksmann et al. · 2009 [cited by applicant]
US 7501496B1 · Endl et al. · 2009 [cited by applicant]
US 7521541B2 · Eigenbrot et al. · 2009 [cited by applicant]
US 7572618B2 · Mintier et al. · 2009 [cited by applicant]
US 7582288B2 · Gillies et al. · 2009 [cited by applicant]
US 7704500B2 · Papadopoulos et al. · 2010 [cited by applicant]
US 7722872B2 · Kroczek · 2010 [cited by applicant]
US 7776577B2 · Kapeller-Libermann et al. · 2010 [cited by applicant]
US 7794710B2 · Chen et al. · 2010 [cited by applicant]
US 7812133B2 · Martin · 2010 [cited by applicant]
US 7868141B2 · Endl et al. · 2011 [cited by applicant]
US 7892540B2 · Chen · 2011 [cited by applicant]
US 7932358B2 · Tamatani et al. · 2011 [cited by applicant]
US 7943743B2 · Korman et al. · 2011 [cited by applicant]
US 7968689B2 · Rosen et al. · 2011 [cited by applicant]
US 7972813B2 · McCormack et al. · 2011 [cited by applicant]
US 7988965B2 · Tsuji et al. · 2011 [cited by applicant]
US 7998478B2 · Tezuka et al. · 2011 [cited by applicant]
US 8008449B2 · Korman et al. · 2011 [cited by applicant]
US 8030457B2 · Jackson et al. · 2011 [cited by applicant]
US 8062640B2 · Sleeman et al. · 2011 [cited by applicant]
US 8080243B2 · Liang et al. · 2011 [cited by applicant]
US 8101175B1 · Croft et al. · 2012 [cited by applicant]
US 8168179B2 · Honjo et al. · 2012 [cited by applicant]
US 8168762B2 · Jackson et al. · 2012 [cited by applicant]
US 8188233B2 · Condra et al. · 2012 [cited by applicant]
US 8188234B2 · Condra et al. · 2012 [cited by applicant]
US 8318905B2 · Kroczek · 2012 [cited by applicant]
US 8344114B2 · Sparrow et al. · 2013 [cited by applicant]
US 8357371B2 · Sleeman et al. · 2013 [cited by applicant]
US 8389690B2 · Tamatani et al. · 2013 [cited by applicant]
US 8399646B2 · Liang et al. · 2013 [cited by applicant]
US 8420098B2 · Camphausen et al. · 2013 [cited by applicant]
US 8426363B2 · Liang et al. · 2013 [cited by applicant]
US 8486647B2 · Haber et al. · 2013 [cited by applicant]
US 8501184B2 · Sleeman et al. · 2013 [cited by applicant]
US 8530414B2 · Davies et al. · 2013 [cited by applicant]
US 8551477B1 · Croft et al. · 2013 [cited by applicant]
US 8563698B2 · Jackson et al. · 2013 [cited by applicant]
US 8598320B2 · Hedrick et al. · 2013 [cited by applicant]
US 8840889B2 · Chen · 2014 [cited by applicant]
US 8916155B2 · Kroczek · 2014 [cited by applicant]
US 8956615B1 · Croft et al. · 2015 [cited by applicant]
US 8962807B2 · Verdonck et al. · 2015 [cited by applicant]
US 8986694B1 · Clube · 2015 [cited by applicant]
US 8992927B1 · Clube · 2015 [cited by applicant]
US 9045545B1 · Clube · 2015 [cited by applicant]
US 9062105B1 · Clube · 2015 [cited by applicant]
US 9067998B1 · Clube · 2015 [cited by applicant]
US 9102725B2 · Korman et al. · 2015 [cited by applicant]
US 9109034B1 · Clube · 2015 [cited by applicant]
US 9139653B1 · Campbell et al. · 2015 [cited by applicant]
US 9150660B1 · Clube · 2015 [cited by applicant]
US 9234043B1 · Campbell et al. · 2016 [cited by applicant]
US 9376493B2 · Faget et al. · 2016 [cited by applicant]
US 9428570B2 · Lawson et al. · 2016 [cited by applicant]
US 9434785B1 · Bland-Ward et al. · 2016 [cited by applicant]
US 9512229B2 · Bland-Ward et al. · 2016 [cited by applicant]
US 9567399B1 · Campbell et al. · 2017 [cited by applicant]
US 9587030B2 · Campbell et al. · 2017 [cited by applicant]
US 9617338B1 · Campbell et al. · 2017 [cited by applicant]
US 9868789B2 · Bland-Ward et al. · 2018 [cited by applicant]
US 9868790B2 · Bland-Ward et al. · 2018 [cited by applicant]
US 10118963B2 · Zhou · 2018 [cited by applicant]
US 10214586B2 · Ludwig et al. · 2019 [cited by applicant]
US 10259880B2 · Campbell et al. · 2019 [cited by applicant]
US 10604576B2 · Campbell et al. · 2020 [cited by applicant]
US 10654935B2 · Campbell et al. · 2020 [cited by applicant]
US 10669342B2 · Campbell et al. · 2020 [cited by applicant]
US 11396550B2 · Campbell et al. · 2022 [cited by applicant]
US 20020045571A1 · Liu et al. · 2002 [cited by applicant]
US 20020064555A1 · Cullen et al. · 2002 [cited by applicant]
US 20020081679A1 · Chiang · 2002 [cited by applicant]
US 20020082259A1 · Ono et al. · 2002 [cited by applicant]
US 20020114814A1 · Gray et al. · 2002 [cited by applicant]
US 20020150576A1 · LaRosa et al. · 2002 [cited by applicant]
US 20020156242A1 · Tamatani et al. · 2002 [cited by applicant]
US 20030119038A1 · Bingham et al. · 2003 [cited by applicant]
US 20030124149A1 · Shalaby et al. · 2003 [cited by applicant]
US 20030158402A1 · Hall et al. · 2003 [cited by applicant]
US 20040009553A1 · Glucksmann et al. · 2004 [cited by applicant]
US 20040023243A1 · Henry et al. · 2004 [cited by applicant]
US 20040038242A1 · Edmonds et al. · 2004 [cited by applicant]
US 20040110226A1 · Lazar et al. · 2004 [cited by applicant]
US 20040191265A1 · Schenerman et al. · 2004 [cited by applicant]
US 20040248177A1 · Abi Fadel et al. · 2004 [cited by applicant]
US 20040265309A1 · Kandel et al. · 2004 [cited by applicant]
US 20050085433A1 · Breidenstein et al. · 2005 [cited by applicant]
US 20050101529A1 · Yue et al. · 2005 [cited by applicant]
US 20050118625A1 · Mounts · 2005 [cited by applicant]
US 20050147612A1 · Yayon et al. · 2005 [cited by applicant]
US 20050175610A1 · Wiegand et al. · 2005 [cited by applicant]
US 20050197285A1 · Rosen et al. · 2005 [cited by applicant]
US 20050260203A1 · Wiegand et al. · 2005 [cited by applicant]
US 20050271656A1 · Huang · 2005 [cited by applicant]
US 20050281822A1 · Cedarbaum et al. · 2005 [cited by applicant]
US 20050281831A1 · Davis-Smyth et al. · 2005 [cited by applicant]
US 20060002929A1 · Khare et al. · 2006 [cited by applicant]
US 20060116508A1 · Glucksmann et al. · 2006 [cited by applicant]
US 20060147945A1 · Edmonds et al. · 2006 [cited by applicant]
US 20060210566A1 · Holash et al. · 2006 [cited by applicant]
US 20060223088A1 · Rosen et al. · 2006 [cited by applicant]
US 20060223090A1 · Rosen et al. · 2006 [cited by applicant]
US 20060246071A1 · Green et al. · 2006 [cited by applicant]
US 20060246483A1 · Rosen et al. · 2006 [cited by applicant]
US 20070015696A1 · Rosen et al. · 2007 [cited by applicant]
US 20070037206A1 · Rosen et al. · 2007 [cited by applicant]
US 20070037748A1 · Stahl et al. · 2007 [cited by applicant]
US 20070041963A1 · Rosen et al. · 2007 [cited by applicant]
US 20070041972A1 · Rother et al. · 2007 [cited by applicant]
US 20070055056A1 · Rosen et al. · 2007 [cited by applicant]
US 20070082345A1 · Ota et al. · 2007 [cited by applicant]
US 20070122378A1 · Freeman et al. · 2007 [cited by applicant]
US 20070224663A1 · Rosen et al. · 2007 [cited by applicant]
US 20070292440A1 · Kenyon et al. · 2007 [cited by applicant]
US 20080008697A1 · Mintier et al. · 2008 [cited by applicant]
US 20080069795A1 · Rabb · 2008 [cited by applicant]
US 20080103090A1 · Rosen et al. · 2008 [cited by applicant]
US 20080113930A1 · Tan et al. · 2008 [cited by applicant]
US 20080279862A1 · Khare · 2008 [cited by applicant]
US 20090053230A1 · Martin · 2009 [cited by applicant]
US 20090055944A1 · Korman et al. · 2009 [cited by applicant]
US 20090142352A1 · Jackson et al. · 2009 [cited by applicant]
US 20090232795A1 · Condra et al. · 2009 [cited by applicant]
US 20090246192A1 · Condra et al. · 2009 [cited by applicant]
US 20090252749A1 · Leister · 2009 [cited by applicant]
US 20090269350A1 · Glucksmann et al. · 2009 [cited by applicant]
US 20090326202A1 · Jackson et al. · 2009 [cited by applicant]
US 20100040610A1 · Sitlani et al. · 2010 [cited by applicant]
US 20100040611A1 · Sparrow et al. · 2010 [cited by applicant]
US 20100041102A1 · Sitlani et al. · 2010 [cited by applicant]
US 20100068194A1 · Kim · 2010 [cited by applicant]
US 20100068199A1 · Liang et al. · 2010 [cited by applicant]
US 20100098712A1 · Adler et al. · 2010 [cited by applicant]
US 20100136028A1 · Sparrow et al. · 2010 [cited by applicant]
US 20100150937A1 · Sparrow et al. · 2010 [cited by applicant]
US 20100166740A1 · Endl et al. · 2010 [cited by applicant]
US 20100166768A1 · Sleeman et al. · 2010 [cited by applicant]
US 20100183591A1 · Baron et al. · 2010 [cited by applicant]
US 20100183612A1 · Peach et al. · 2010 [cited by applicant]
US 20100203056A1 · Irving et al. · 2010 [cited by applicant]
US 20100233177A1 · Yowe et al. · 2010 [cited by applicant]
US 20100291099A1 · Glucksmann et al. · 2010 [cited by applicant]
US 20100323359A1 · MacDonald et al. · 2010 [cited by applicant]
US 20110027287A1 · Jackson et al. · 2011 [cited by applicant]
US 20110033451A1 · Carreno et al. · 2011 [cited by applicant]
US 20110033465A1 · Hedrick et al. · 2011 [cited by applicant]
US 20110065902A1 · Sleeman et al. · 2011 [cited by applicant]
US 20110070239A1 · Endl et al. · 2011 [cited by applicant]
US 20110091481A1 · Burnette · 2011 [cited by applicant]
US 20110105726A1 · Rosen et al. · 2011 [cited by applicant]
US 20110117011A1 · Jackson et al. · 2011 [cited by applicant]
US 20110135662A1 · Finney et al. · 2011 [cited by applicant]
US 20110142849A1 · Rue et al. · 2011 [cited by applicant]
US 20110229489A1 · Pons et al. · 2011 [cited by applicant]
US 20110230392A1 · Chiang et al. · 2011 [cited by applicant]
US 20110256148A1 · Sleeman et al. · 2011 [cited by applicant]
US 20110274702A1 · Lanzavecchia · 2011 [cited by examiner]
US 20110307966A1 · MacDonald et al. · 2011 [cited by applicant]
US 20120014951A1 · Liang et al. · 2012 [cited by applicant]
US 20120015435A1 · Liang et al. · 2012 [cited by applicant]
US 20120020975A1 · Jackson et al. · 2012 [cited by applicant]
US 20120020976A1 · Jackson et al. · 2012 [cited by applicant]
US 20120027751A1 · Rennert · 2012 [cited by applicant]
US 20120027765A1 · Jackson et al. · 2012 [cited by applicant]
US 20120058906A1 · Smider et al. · 2012 [cited by applicant]
US 20120064621A1 · Papadopoulos et al. · 2012 [cited by applicant]
US 20120076799A1 · Sparrow et al. · 2012 [cited by applicant]
US 20120077964A1 · Sparrow et al. · 2012 [cited by applicant]
US 20120082679A1 · Sparrow et al. · 2012 [cited by applicant]
US 20120082680A1 · Sitlani et al. · 2012 [cited by applicant]
US 20120185956A1 · Gingras · 2012 [cited by applicant]
US 20120195910A1 · Wu et al. · 2012 [cited by applicant]
US 20120208208A1 · Ni et al. · 2012 [cited by applicant]
US 20120208209A1 · Ichetovkin et al. · 2012 [cited by applicant]
US 20120213794A1 · Luo et al. · 2012 [cited by applicant]
US 20120213797A1 · Jackson et al. · 2012 [cited by applicant]
US 20120219558A1 · Ni et al. · 2012 [cited by applicant]
US 20120231005A1 · Luo et al. · 2012 [cited by applicant]
US 20120251544A1 · Jackson et al. · 2012 [cited by applicant]
US 20120269723A1 · Brickmann et al. · 2012 [cited by applicant]
US 20120301461A1 · Condra et al. · 2012 [cited by applicant]
US 20120321879A1 · Teutsch et al. · 2012 [cited by applicant]
US 20120328616A1 · Li et al. · 2012 [cited by applicant]
US 20130018175A1 · Verdonck et al. · 2013 [cited by applicant]
US 20130052201A1 · Jackson et al. · 2013 [cited by applicant]
US 20130058944A1 · Jackson et al. · 2013 [cited by applicant]
US 20130064825A1 · Chan et al. · 2013 [cited by applicant]
US 20130064834A1 · Sleeman et al. · 2013 [cited by applicant]
US 20130071379A1 · Condra et al. · 2013 [cited by applicant]
US 20130071405A1 · Davies et al. · 2013 [cited by applicant]
US 20130072665A1 · Jackson et al. · 2013 [cited by applicant]
US 20130079501A1 · Jackson et al. · 2013 [cited by applicant]
US 20130079502A1 · Jackson et al. · 2013 [cited by applicant]
US 20130085265A1 · Jackson et al. · 2013 [cited by applicant]
US 20130085266A1 · Sleeman et al. · 2013 [cited by applicant]
US 20130095108A1 · Jablonska et al. · 2013 [cited by applicant]
US 20130095109A1 · Nadler et al. · 2013 [cited by applicant]
US 20130115171A1 · McDonough · 2013 [cited by applicant]
US 20130115223A1 · Sparrow et al. · 2013 [cited by applicant]
US 20130142783A1 · Coyle et al. · 2013 [cited by applicant]
US 20130183315A1 · Attinger et al. · 2013 [cited by applicant]
US 20130189278A1 · Sitlani et al. · 2013 [cited by applicant]
US 20130245235A1 · Jackson et al. · 2013 [cited by applicant]
US 20130273069A1 · Liang et al. · 2013 [cited by applicant]
US 20130310324A1 · Flinspach et al. · 2013 [cited by applicant]
US 20140037648A1 · Corti · 2014 [cited by examiner]
US 20140044703A1 · Kato et al. · 2014 [cited by applicant]
US 20140086932A1 · Traber et al. · 2014 [cited by applicant]
US 20140093497A1 · Reimann et al. · 2014 [cited by applicant]
US 20140161794A1 · Lugovsky et al. · 2014 [cited by applicant]
US 20140165219A1 · Leppert et al. · 2014 [cited by applicant]
US 20140170157A1 · Agarwal et al. · 2014 [cited by applicant]
US 20140286897A1 · Podack et al. · 2014 [cited by applicant]
US 20140322132A1 · Vitalis et al. · 2014 [cited by applicant]
US 20150203580A1 · Papadopoulos et al. · 2015 [cited by applicant]
US 20150239978A1 · Marodon et al. · 2015 [cited by applicant]
US 20150307620A1 · Vella et al. · 2015 [cited by applicant]
US 20160000909A1 · Eisenbach-Schwartz et al. · 2016 [cited by applicant]
US 20160002336A1 · Chen · 2016 [cited by applicant]
US 20160024211A1 · Chen · 2016 [cited by applicant]
US 20160145344A1 · Akbari · 2016 [cited by applicant]
US 20160215059A1 · Liu et al. · 2016 [cited by applicant]
US 20160264666A1 · Faget et al. · 2016 [cited by applicant]
US 20160264675A1 · Bland-Ward et al. · 2016 [cited by applicant]
US 20160304610A1 · Sazinsky et al. · 2016 [cited by applicant]
US 20160361364A1 · Carbascio et al. · 2016 [cited by applicant]
US 20160368997A1 · Campbell et al. · 2016 [cited by applicant]
US 20170002083A1 · Campbell et al. · 2017 [cited by applicant]
US 20170037137A1 · Bland-Ward et al. · 2017 [cited by applicant]
US 20170044250A1 · Campbell et al. · 2017 [cited by applicant]
US 20170260279A1 · Bland-Ward et al. · 2017 [cited by applicant]
US 20170320956A1 · Campbell et al. · 2017 [cited by applicant]
US 20170327586A1 · Bland-Ward et al. · 2017 [cited by applicant]
US 20170327587A1 · Campbell et al. · 2017 [cited by applicant]
US 20180305464A1 · Li et al. · 2018 [cited by applicant]
US 20190077867A1 · Zhu et al. · 2019 [cited by applicant]
US 20190275084A1 · Bland-Ward et al. · 2019 [cited by applicant]
US 20190276547A1 · Campbell et al. · 2019 [cited by applicant]
US 20190330351A1 · Campbell et al. · 2019 [cited by applicant]
US 20200231692A1 · Hu et al. · 2020 [cited by applicant]
US 20210087287A1 · Campbell et al. · 2021 [cited by applicant]
US 20210380699A1 · Campbell et al. · 2021 [cited by applicant]
US 20210395378A1 · Campbell et al. · 2021 [cited by applicant]
US 20220372153A1 · Bland-Ward et al. · 2022 [cited by applicant]
CN 101023102 · 2007 [cited by applicant]
CN 101248089 · 2008 [cited by applicant]
CN 101374865 · 2009 [cited by applicant]
CN 103221427 · 2013 [cited by applicant]
EP 0438474 · 1996 [cited by applicant]
EP 0463151 · 1996 [cited by applicant]
EP 0546073 · 1997 [cited by applicant]
EP 0984023 · 2000 [cited by applicant]
EP 1067182 · 2001 [cited by applicant]
EP 1125585 · 2001 [cited by applicant]
EP 1158004 · 2001 [cited by applicant]
EP 0996622 · 2002 [cited by applicant]
EP 1374901 · 2004 [cited by applicant]
EP 1502920 · 2005 [cited by applicant]
EP 1514933 · 2005 [cited by applicant]
EP 1286668 · 2005 [cited by applicant]
EP 1618212 · 2007 [cited by applicant]
EP 2481758 · 2012 [cited by applicant]
EP 1740617 · 2013 [cited by applicant]
EP 2650016 · 2013 [cited by applicant]
EP 2691419 · 2016 [cited by applicant]
EP 3369745 · 2018 [cited by applicant]
EP 2812022 · 2019 [cited by applicant]
EP 3495391 · 2019 [cited by applicant]
JP 2005130764 · 2005 [cited by applicant]
JP 2008512995 · 2008 [cited by applicant]
JP 2009518005 · 2009 [cited by applicant]
JP 2017513813 · 2017 [cited by applicant]
RU 2540490 · 2015 [cited by applicant]
WO 8504880A1 · 1985 [cited by applicant]
WO WO1985004880 · 1985 [cited by applicant]
WO WO1990002809 · 1990 [cited by applicant]
WO WO1991004329 · 1991 [cited by applicant]
WO WO1991009967 · 1991 [cited by applicant]
WO WO1991010737 · 1991 [cited by applicant]
WO WO1991013166 · 1991 [cited by applicant]
WO WO1992001047 · 1992 [cited by applicant]
WO WO1992002551 · 1992 [cited by applicant]
WO WO1992008495 · 1992 [cited by applicant]
WO WO1992008801 · 1992 [cited by applicant]
WO WO1992018619 · 1992 [cited by applicant]
WO WO1992022583 · 1992 [cited by applicant]
WO WO1993011236 · 1993 [cited by applicant]
WO WO1993012227 · 1993 [cited by applicant]
WO WO1993020849 · 1993 [cited by applicant]
WO WO1995015982 · 1995 [cited by applicant]
WO WO1995020401 · 1995 [cited by applicant]
WO WO1995021915 · 1995 [cited by applicant]
WO WO1996008570 · 1996 [cited by applicant]
WO WO1997044453 · 1997 [cited by applicant]
WO WO1997049805 · 1997 [cited by applicant]
WO WO1998003821 · 1998 [cited by applicant]
WO WO1998013071 · 1998 [cited by applicant]
WO WO1998020734 · 1998 [cited by applicant]
WO WO1998024893 · 1998 [cited by applicant]
WO WO1998025971 · 1998 [cited by applicant]
WO WO1999003859 · 1999 [cited by applicant]
WO WO1999003996 · 1999 [cited by applicant]
WO WO1999015553 · 1999 [cited by applicant]
WO WO1999029732 · 1999 [cited by applicant]
WO WO1999043713 · 1999 [cited by applicant]
WO WO1999052562 · 1999 [cited by applicant]
WO WO1999053958 · 1999 [cited by applicant]
WO WO1999060128 · 1999 [cited by applicant]
WO WO2000011033 · 2000 [cited by applicant]
WO WO2000040615 · 2000 [cited by applicant]
WO WO2000047228 · 2000 [cited by applicant]
WO WO2000076310 · 2000 [cited by applicant]
WO WO2001007081 · 2001 [cited by applicant]
WO WO2001010912 · 2001 [cited by applicant]
WO WO2001014424 · 2001 [cited by applicant]
WO WO2001031007 · 2001 [cited by applicant]
WO WO2001057081 · 2001 [cited by applicant]
WO WO2001058957 · 2001 [cited by applicant]
WO WO2001087981 · 2001 [cited by applicant]
WO WO2001098468 · 2001 [cited by applicant]
WO WO2002000243 · 2002 [cited by applicant]
WO WO2002002143 · 2002 [cited by applicant]
WO WO2002014358 · 2002 [cited by applicant]
WO WO2002046383 · 2002 [cited by applicant]
WO WO2002057435 · 2002 [cited by applicant]
WO WO2002066514 · 2002 [cited by applicant]
WO WO2002072605 · 2002 [cited by applicant]
WO WO2002079232 · 2002 [cited by applicant]
WO WO2002079415 · 2002 [cited by applicant]
WO WO2002090526 · 2002 [cited by applicant]