Recombinant human IGA-J. chain dimer

• US 6,063,905 A
• Filed: 01/07/1997
• Issued: 05/16/2000
• Est. Priority Date: 01/07/1997
• Status: Expired due to Fees

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: United States Department Of Health And Human Services, Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Carayannopoulos, Leon N., Max, Edward E., Capra, J. Donald, Hexham, Jonathan M.
• Primary Examiner(s): EYLER, YVONNE L
• Application Number:
  US08/779,597
• Time in Patent Office: 1,225 Days
• Field of Search: 530/387.1, 530/387.3, 530/390.1, 424/130.1, 424/133.1, 424/136.1, 435/328
• US Class Current: 530/387.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/1063 env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Disclosed are compositions and methods of use that comprise engineered IgA antibodies that, when administered to a host are secreted across the epithelium into the mucosal barriers of the body providing external passive immunotherapy against agents such as viral, bacterial and eukaryotic pathogens. Also disclosed are mini antibodies comprising the minimal transcytosis domains.

Claims

1. A mini-IgA antibody comprising a VH domain fused to a first IgA1 Cα

3 domain including a tailpiece, and a VL domain fused to a second IgA1 Cα

3 domain including a tailpiece, wherein said VL and VH domains constitute an antigen or hapten recognition site, and wherein said mini-IgA antibody lacks other Cα

domains.

2. A dimeric IgA antibody comprising two mini-IgA antibodies of claim 1 connected by a J-chain.

3. The antibody of claim 2 dispersed in a pharmaceutically acceptable solution.

4. The antibody of claim 1, wherein said Cα

3 domains are human Cα

3 domains.

5. The antibody of claim 1, wherein said antigen is a viral, bacterial or protozoan antigen.

6. The antibody of claim 5, wherein said antigen is a virus.

7. The antibody of claim 6, wherein said virus is influenza A, B or C, parainfluenza, paramyxovirus, Newcastle disease virus, respiratory syncytial virus, measles, mumps, adenovirus, adenoassociated virus, parvovirus, Epstein-Barr virus, rhinovirus, coxsackievirus, echovirus, reovirus, rhabdovirus, lymphocytic choriomeningitis, coronavirus, poliovirus, herpes simplex, human immunodeficiency virus, cytomegalovirus, papillomavirus, virus B, varicella-zoster, poxvirus, rubella, rabies, picornavirus or rotavirus.

8. The antibody of claim 7, wherein said virus is a human immunodeficiency virus.

9. The antibody of claim 8, wherein said antibody is immunoreactive with gp120 of HIV.

10. The antibody of claim 7, wherein said virus is an influenza A virus.

11. The antibody of claim 7, wherein said virus is an influenza B virus.

12. The antibody of claim 7, wherein said virus is an influenza C virus.

13. The antibody of claim 7, wherein said virus is a parainfluenza virus.

14. The antibody of claim 7, wherein said virus is a paramyxovirus.

15. The antibody of claim 7, wherein said virus is a Newcastle disease virus.

16. The antibody of claim 7, wherein said virus is a respiratory syncytial virus.

17. The antibody of claim 7, wherein said virus is a measles virus.

18. The antibody of claim 7, wherein said virus is a mumps virus.

19. The antibody of claim 7, wherein said virus is an adenovirus.

20. The antibody of claim 7, wherein said virus is an adenoassociated virus.

21. The antibody of claim 7, wherein said virus is a parvovirus.

22. The antibody of claim 7, wherein said virus is an Epstein-Barr virus.

23. The antibody of claim 7, wherein said virus is a rhinovirus.

24. The antibody of claim 7, wherein said virus is a coxsackievirus.

25. The antibody of claim 7, wherein said virus is an echovirus.

26. The antibody of claim 7, wherein said virus is a reovirus.

27. The antibody of claim 7, wherein said virus is a rhabdovirus.

28. The antibody of claim 7, wherein said virus is a lymphocytic choriomeningitis virus.

29. The antibody of claim 7, wherein said virus is a coronavirus.

30. The antibody of claim 7, wherein said virus is a poliovirus.

31. The antibody of claim 7, wherein said virus is a herpes simplex virus.

32. The antibody of claim 7, wherein said virus is a cytomegalovirus.

33. The antibody of claim 7, wherein said virus is a papillomavirus.

34. The antibody of claim 7, wherein said virus is a virus B.

35. The antibody of claim 7, wherein said virus is a varicella-zoster virus.

36. The antibody of claim 7, wherein said virus is a poxvirus.

37. The antibody of claim 7, wherein said virus is a rubella virus.

38. The antibody of claim 7, wherein said virus is a rabies virus.

39. The antibody of claim 7, wherein said virus is a picornavirus.

40. The antibody of claim 7, wherein said virus is a rotavirus.

41. The antibody of claim 5, wherein said antigen is a bacteria.

42. The antibody of claim 41, wherein said bacteria is pneumococci, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus equi, Streptococcus canis, Streptococcus bovis, Streptococcus equinus, Streptococcuts anginosus, Streptococcus sanguis, Streptococcus salivarius, Streptococclts mitis, Streptococcus mutans, viridans streptococci, peptostreptococci, Enterococcus faecalis, Enterococcus faecium, Staphylococcus epidennidis, Staphylococcus aureus, Hemophilus influenzae, Pseudomonas aeruginosa, Pseudomonas pseudomallei, Pseudomonas mallei, Brucella melitensis, Brucella suis, Brucella abortus, Bordetella pertussis, Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis, Corynebacterium diphtheriae, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis, Corynebacterium pseudodiphtheriticum, Corynebacterium urealyticum, Corynebacterium hemolyticum, Corynebacterium equi, Listeria monocytogenes, Nocordia asteroides, Actinomycetes, Treponema pallidum, Leptospirosa, Klebsiella pneumoniae, Escherichia coli, Proteus, Serratia, Acinetobacter, Yersinia pestis, Francisella tulrensis, Enterobacter, Bacteriodes or Legionella.

43. The antibody of claim 41, wherein said bacteria is a pneumococci.

44. The antibody of claim 41, wherein said bacteria is a Streptococcus pyogenes.

45. The antibody of claim 41, wherein said bacteria is a Streptococus agalactiae.

46. The antibody of claim 41, wherein said bacteria is a Streptococcus equi.

47. The antibody of claim 41, wherein said bacteria is a Streptococcus canis.

48. The antibody of claim 41, wherein said bacteria is a Streptococcus bovis.

49. The antibody of claim 41, wherein said bacteria is a Streptococcus equoius.

50. The antibody of claim 41, wherein said bacteria is a Streptococcus anginosus.

51. The antibody of claim 41, wherein said bacteria is a Streptococcus sanguis.

52. The antibody of claim 41, wherein said bacteria is a Streptococcus salivarius.

53. The antibody of claim 41, wherein said bacteria is a Streptococcus mitis.

54. The antibody of claim 41, wherein said bacteria is a Streptococcus mutans.

55. The antibody of claim 41, wherein said bacteria is a viridans streptococci.

56. The antibody of claim 41, wherein said bacteria is a peptostreptococci.

57. The antibody of claim 41, wherein said bacteria is a Enterococcus faecalis.

58. The antibody of claim 41, wherein said bacteria is a Enterococcus faecium.

59. The antibody of claim 41, wherein said bacteria is a Staphylococcus epidermidis.

60. The antibody of claim 41, wherein said bacteria is a Staphylococcits aureus.

61. The antibody of claim 41, wherein said bacteria is a Hemophilus influenzae.

62. The antibody of claim 41, wherein said bacteria is a Pseudomonas aeruginosa.

63. The antibody of claim 41, wherein said bacteria is a Pseudomonas pseudomallei.

64. The antibody of claim 41, wherein said bacteria is a Pseudomonas mallei.

65. The antibody of claim 41, wherein said bacteria is a Brucella melitensis.

66. The antibody of claim 41, wherein said bacteria is a Brucella suis.

67. The antibody of claim 41, wherein said bacteria is a Brucella abortus.

68. The antibody of claim 41, wherein said bacteria is a Bordetella pertussis.

69. The antibody of claim 41, wherein said bacteria is a Neisseria meningitidis.

70. The antibody of claim 41, wherein said bacteria is a Neisseria gonorrhoeae.

71. The antibody of claim 41, wherein said bacteria is a Moraxella catarrrhalis.

72. The antibody of claim 41, wherein said bacteria is a Corynebacterium diphtheriae.

73. The antibody of claim 41, wherein said bacteria is a Corynebacterium ulcerans.

74. The antibody of claim 41, wherein said bacteria is a Corynebacterium pseudotuberculosis.

75. The antibody of claim 41, wherein said bacteria is a Corynebacterium pseudodiphtheriticum.

76. The antibody of claim 41, wherein said bacteria is a Corynebacterium urealyticum.

77. The antibody of claim 41, wherein said bacteria is a Corynebacterium hemolyticum.

78. The antibody of claim 41, wherein said bacteria is a Corynebacterium equi.

79. The antibody of claim 41, wherein said bacteria is a Listeria monocytogenes.

80. The antibody of claim 41, wherein said bacteria is a Nocordia asteroices.

81. The antibody of claim 41, wherein said bacteria is an Actinomycetes.

82. The antibody of claim 41, wherein said bacteria is a Treponema pallidum.

83. The antibody of claim 41, wherein said bacteria is a Leptospirosa.

84. The antibody of claim 41, wherein said bacteria is a Klebsiella pneumoniae.

85. The antibody of claim 41, wherein said bacteria is a Escherichia coli.

86. The antibody of claim 41, wherein said bacteria is a Proteus.

87. The antibody of claim 41, wherein said bacteria is a Serratia.

88. The antibody of claim 41, wherein said bacteria is an Acinetobacter.

89. The antibody of claim 41, wherein said bacteria is a Yersinia pestis.

90. The antibody of claim 41, wherein said bacteria is a Francisella tularensis.

91. The antibody of claim 41, wherein said bacteria is a Enterobacter.

92. The antibody of claim 41, wherein said bacteria is a Bacteriodes.

93. The antibody of claim 41, wherein said bacteria is a Legionella.

94. The antibody of claim 5, wherein said antigen is a protozoan.

95. The antibody of claim 94, wherein said protozoan is a Cryptosporidium.

96. The antibody of claim 94, wherein said protozoan is an Isospora belli.

97. The antibody of claim 94, wherein said protozoan is a Toxoplasma gondii.

98. The antibody of claim 94, wherein said protozoan is a Trichomonas vaginalis.

99. The antibody of claim 94, wherein said protozoan is a Cyclospora.

100. The antibody of claim 94, wherein said protozoan is a Chlamydia trachomatis.

101. The antibody of claim 94, wherein said protozoan is a Chlamydia psittaci.

102. The antibody of claim 94, wherein said protozoan is a Chlamydia pneumoniae.