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Title:
ANTI-INFLAMMATORY THERAPY FOR INFLAMMATORY MEDIATED INFECTION
Document Type and Number:
WIPO Patent Application WO/2000/069255
Kind Code:
A1
Abstract:
Provided are methods for inhibiting the progression of an inflammatory mediated mucosal infection. The methods include administering an effective amount of an anti-inflammatory agent. Also provided are compositions and articles of manufacture for preventing, and inhibiting the activation and progression of a mucosal infection.

Inventors:
ANTON PETER A (US)
POLES MICHAEL A (US)
GIORGI JANIS V (US)
ELLIOTT JULIE E (US)
Application Number:
PCT/US2000/013142
Publication Date:
November 23, 2000
Filing Date:
May 12, 2000
Export Citation:
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Assignee:
UNIV CALIFORNIA (US)
ANTON PETER A (US)
POLES MICHAEL A (US)
GIORGI JANIS V (US)
ELLIOTT JULIE E (US)
International Classes:
A61F6/04; A61F6/06; A61F6/14; A61K9/06; A61K9/107; A61K9/12; A61K31/00; A61K31/192; A61K31/454; A61K31/472; A61K9/02; A61K31/4725; A61K31/496; A61K31/513; A61K31/536; A61K31/5513; A61K31/573; A61K31/60; A61K31/603; A61K31/606; A61K31/7072; A61K31/708; A61K31/7088; A61K36/18; A61K38/00; A61K38/17; A61K38/20; A61K39/395; A61K45/06; A61K48/00; A61P1/04; A61P11/02; A61P15/02; A61P31/04; A61P31/12; A61P31/18; A61P43/00; (IPC1-7): A01K37/18; A01K43/04; A61K31/60; A61K31/70; A61K36/16; A61K38/00; A61K38/43; A61K39/00; A61K39/395; A61K45/00
Foreign References:
US5891924A1999-04-06
US5605885A1997-02-25
US5098927A1992-03-24
Other References:
BARCELLINI ET AL.: "Inhibitory influences of alpha-MSH peptides on HIV-1 expression in monocytic cells'", 12TH WORLD INT AIDS CONF, vol. 12, no. (ABST. 60685), pages 1126 - 1127, XP002950626
GOLETTI ET AL.: "The in vitro induction of human immunodeficiency virus (HIV) replication in purified protein derivative-positive HIV-infected persons by recall of a balance of the effects of endogenous interleukin-2 and proinflammatory andantiinflammatory cytokines", JOURNAL OF INFECTIOUS DISEASES., vol. 177, no. 5, May 1998 (1998-05-01), pages 1332 - 1338, XP002930393
ORNSTEIN ET AL.: "The antiinflammatory and antiviral effects of hydroxychloroquine in two patients with acquired immunodeficiency syndrome and active inflammatory arthritis", ARTHRITIS AND RHEUMATISM,, vol. 39, no. 1, January 1996 (1996-01-01), pages 157 - 161, XP002930394
IMAIZUMI ET AL.: "Effect of long term therapy with glycyrrhizin for HIV infection in a hemophilia patient", INT CONF AIDS, vol. 10, no. 1 (ABST. PB0326), pages 224, XP002950627
BABA ET AL.: "Anti-inflammatory alkaloid cepharanthine inhibits HIV-1 replication in chronically infected cells", INT. CONF. AIDS, no. 60049, 1998, pages 1010, XP002909662
BIOCHEMICAL BIOPHYSICAL RESEARCH COMMUNICATIONS,, vol. 208, no. 2, 17 March 1995 (1995-03-17), pages 779 - 785, XP002930395
Attorney, Agent or Firm:
Wetherell Jr., John R. (CA, US)
Download PDF:
Claims:
WHAT IS CLAIMED IS:
1. A method of inhibiting activation of a retrovirus, comprising contacting a cell infected with the virus with a virusactivation inhibiting amount of an anti inflammatory agent and an antiviral agent.
2. The method of claim 1, wherein the retrovirus is a lentivirus.
3. The method of claim 2, wherein the lentivirus is an immunodeficiency virus.
4. The method of claim 3, wherein the immunodeficiency virus is selected from the group consisting of human immunodeficiency virus (HIV) type 1, HIVtype 2, and simian immunodeficiency virus (SIV).
5. The method of claim 1, wherein the contacting is invivo.
6. The method of claim 1, wherein the contacting is in vitro.
7. The method of claim 1, wherein the cell is a mammalian cell.
8. The method of claim 7, wherein the mammalian cell is a human cell.
9. The method of claim 1, wherein the antiviral agent inhibits viral fusion or cell entry, viral reverse transcription or nucleic acid replication, viral integration into cell DNA, viral budding or release from a cell, production of infectious virus, or an enzyme associated with viral fusion or infection, reverse transcription or nucleic acid replication, viral integration into cell DNA, viral budding or release from a cell, or production of infectious virus.
10. The method of claim 1, wherein the antiviral agent is a polypeptide or functional mimetic.
11. The method of claim 10, wherein the polypeptide or functional mimetic binds to the virus or a cell surface receptor.
12. The method of claim 10, wherein the polypeptide is a ligand, a viral receptor, an antibody or a fragment thereof.
13. The method of claim 9, wherein the enzyme is a protease, a reverse transcriptase or an integrase.
14. The method of claim 1, wherein the antiviral agent is selected from the group consisting of a protease inhibitor, a nucleoside reverse transcriptase inhibitor, a nonnucleoside reverse transcriptase inhibitor, an integrase inhbitor and mixtures thereof.
15. The method of claim 14, wherein the nucleoside inhibitor is zidovudine (AZT), stavudine (d4T), larnivudine (3TC), didanosine (DDI), zalcitabine (ddC), abacavir and mixtures thereof.
16. The method of claim 14, wherein the nonnucleoside inhibitor is selected from the group consisting of nevirapine, delavirdine and efavirenz.
17. The method of claim 1, wherein the antiviral agent is a protease inhibitor.
18. The method of claim 17, wherein the protease inhibitor is saquinavir, ritonavir, indinavir, nelfinavir, or amprenavir.
19. The method of claim 1, wherein the antiinflammatory agent decreases the recruitment of inflammatory cells, decreases the production of chemokines, decreases the production of proinflammatory cytokines, or inhibits interaction of a chemokine receptor with its ligand.
20. The method of claim 1, wherein the antiinflammatory agent is selected from the group consisting of an antiinflammatory antibody, an antiinflammatory peptide, an antiinflammatory cytokine, an antiinflammatory chemokine, an antiinflammatory nucleic acid, a steroid, a nonsteroidal antiinflammatory drug, a 5ASA product, and combinations thereof.
21. The method of claim 20, wherein the antiinflammatory antibody is selected from the group consisting of an anticytokine antibody, an anticytokine receptor antibody, an antichemokine antibody, an antichemokine receptor antibody, an antiproinflammatory peptide antibody, and combinations thereof.
22. The method of claim 20, wherein the antiinflammatory peptide is selected from the group consisting of an LFA adhesion molecule antagonist, a cytokine receptor antagonist, a transcription factor, and a soluble TNFa receptor polypeptide.
23. The method of claim 20, wherein the antiinflammatory cytokine is selected from the group consisting of IL4, IL10, IL13, IL16, and combinations thereof.
24. The method of claim 20, wherein the antiinflammatory nucleic acid is selected from the group consisting of a ribozyme, a nucleic acid encoding an anti inflammatory peptide, an antisense nucleic acid, and combinations thereof.
25. The method of claim 24, wherein the antisense nucleic acid hybridizes to a nucleic acid encoding a cytokine receptor, an inflammatory cytokine, a chemokine receptor, or a chemokine.
26. The method of claim 20, wherein the steroid is a glucocorticoid.
27. The method of claim 20, wherein the steroid is selected from the group consisting of flunisolide, triamcinoline, triamcinoline acetonide, beclomethasone diproprionate, betamethasone diproprionate, hydrocortisone, cortisone, dexamethasone, budesonide, prednisone, methyl prednisolone, prednisolone, and combinations thereof.
28. The method of claim 20, wherein the nonsteroidal antiinflammatory drug is selected from the group of salicylic acid derivatives consisting of salicylic acid, sodium thiosalicylate, choline salicylate, magnesium salicylate, diflunisal, ibuprofen, naproxen, sulindac, diflunisal, salicylsalicylic acid, choline magnesium trisalicylate, acetylsalicylic acid, salsalate, sodium salicylate and combinations thereof.
29. The method of claim 20, wherein the nonsteroidal antiinflammatory drug is selected from the group consisting of flurbiprofen, fenoprofen, naburnetone, ketoprofen, piroxicam, indomethacin, tolmetin, meclofanamate sodium, mefenamic acid, etodolac, ketorolac tromethamine, diclofenac, oxaprozin, bromfenac sodium, rofecoxib, suprofen, fenbuprofen, fluprofen, thalidomide, evening primrose oil, single isomers thereof and combinations thereof.
30. The method of claim 20, wherein the 5ASA product is selected from the group consisting of mesalamine, balsalazide, ipsalazide, olsalazine, sulfasalazine and mixtures thereof.
31. A method for inhibiting an inflammatory mediated infection of mucosal tissue, comprising contacting the tissue with an inhibiting effective amount of an anti inflammatory agent and an antiviral agent.
32. The method of claim 31, wherein the inflammatory mediated infection is caused by a virus.
33. The method of claim 32, wherein the virus is a retrovirus.
34. The method of claim 33, wherein the retrovirus is a lentivirus.
35. The method of claim 34, wherein the lentivirus is an immunodeficiency virus.
36. The method of claim 35, wherein the immunodeficiency virus is selected from the group consisting of human immunodeficiency virus (HIV) type 1, HIVtype 2, and simian immunodeficiency virus (SIV).
37. The method of claim 31, wherein the contacting is in vivo.
38. The method of claim 31, wherein the contacting is in vitro.
39. The method of claim 31, wherein the contacting is ex vivo.
40. The method of claim 31, wherein the tissue is a mammalian tissue.
41. The method of claim 40, wherein the mammalian tissue is a human tissue.
42. The method of claim 31, wherein the mucosal tissue is a vaginal tissue, a gastro intestinal tissue, a nasal tissue or a tissue of the lower GI tract.
43. The method of claim 31, wherein the contacting is by administering the anti inflammatory agent locally or systemically, prior to, simultaneously with or after administering the antiviral agent.
44. The method of claim 43, wherein the administration is by locally contacting by topical administration.
45. The method of claim 43, wherein the systemic administration is by intravenous, oral or parenteral administration.
46. The method of claim 31, wherein the antiviral agent inhibits viral fusion or cell entry, viral reverse transcription or nucleic acid replication, viral integration into cell DNA, viral budding or release from a cell, production of infectious virus, or an enzyme associated with viral fusion or infection, reverse transcription or nucleic acid replication, viral integration into cell DNA, viral budding or release from a cell, or production of infectious virus.
47. The method of claim 31, wherein the antiviral agent is a polypeptide or functional mimetic.
48. The method of claim 47, wherein the polypeptide or functional mimetic binds to the virus or a cell surface receptor.
49. The method of claim 47, wherein the polypeptide is a ligand, a viral receptor, an antibody or a fragment thereof.
50. The method of claim 46, wherein the enzyme is a protease, a reverse transcriptase or an integrase.
51. The method of claim 31, wherein the antiviral agent is selected from the group consisting of a protease inhibitor, a nucleoside reverse transcriptase inhibitor, a nonnucleoside reverse transcriptase inhibitor, an integrase inhibitor and mixtures thereof.
52. The method of claim 51, wherein the nucleoside inhibitor is zidovudine (AZT), stavudine (d4T), larnivudine (3TC), didanosine (DDI), zalcitabine (ddC), abacavir and mixtures thereof.
53. The method of claim 51, wherein the nonnucleoside inhibitor is nevirapine, delavirdine, or efavirenz.
54. The method of claim 31, wherein the antiviral agent is a protease inhibitor, a reverse transcriptase inhibitor or an integrase inhibitor.
55. The method of claim 54, wherein the protease inhibitor is saquinavir, ritonavir, indinavir, nelfinavir, or amprenavir.
56. The method of claim 31, wherein the antiinflammatory agent decreases the recruitment of inflammatory cells, decreases the production of chemokines, decreases the production of proinflammatory cytokines, or inhibits the interaction of a chemokine receptor with its ligand.
57. The method of claim 31, wherein the antiinflammatory agent is selected from the group consisting of an antiinflammatory antibody, an antiinflammatory peptide, an antiinflammatory cytokine, an antiinflammatory chemokine, an antiinflammatory nucleic acid, a steroid, a nonsteroidal antiinflammatory drug, 5ASA products, and combinations thereof.
58. The method of claim 57, wherein the antiinflammatory antibody is selected from the group consisting of an anticytokine antibody, an anticytokine receptor antibody, an antichemokine antibody, an antichemokine receptor antibody, an antiproinflammatory peptide antibody, and combinations thereof.
59. The method of claim 57, wherein the antiinflammatory peptide is selected from the group consisting of an LFA1 antagonist, a cytokine receptor antagonist, a transcription factor, and a soluble TNFa receptor.
60. The method of claim 57, wherein the antiinflammatory cytokine is selected from the group consisting of IL4, IL10, IL13, IL16, and combinations thereof.
61. The method of claim 57, wherein the antiinflammatory nucleic acid is selected from the group consisting of a ribozyme, a nucleic acid encoding an anti inflammatory peptide, an antisense nucleic acid, and combinations thereof.
62. The method of claim 61, wherein the antisense nucleic acid hybridizes to nucleic acid encoding a cytokine receptor, an inflammatory cytokine, a chemokine, or a chemokine receptor.
63. The method of claim 57, wherein the steroid is a glucocorticoid.
64. The method of claim 57, wherein the steroid is selected from the group consisting of flunisolide, triamcinoline, triamcinoline acetonide, beclomethasone diproprionate, betamethasone diproprionate, hydrocortisone, cortisone, dexamethasone, budesonide, prednisone, methyl prednisolone, prednisolone, and combinations thereof.
65. The method of claim 57, wherein the nonsteroidal antiinflammatory drug is selected from the group of salicylic acid derivatives consisting of salicylic acid, sodium thiosalicylate, choline salicylate, magnesium salicylate, diflunisal, ibuprofen, naproxen, sulindac, diflunisal, salicylsalicylic acid, choline magnesium trisalicylate, acetylsalicylic acid, salsalate, sodium salicylate and combinations thereof.
66. The method of claim 57, wherein the nonsteroidal antiinflammatory drug is selected from the group consisting of flurbiprofen, fenoprofen, naburnetone, ketoprofen, piroxicam, indomethacin, tolmetin, meclofanamate sodium, mefenamic acid, etodolac, ketorolac tromethamine, diclofenac, oxaprozin, bromfenac sodium, rofecoxib, suprofen, fenbuprofen, fluprofen, thalidomide, evening primrose oil, single isomers thereof and combinations thereof.
67. The method of claim 57, wherein the 5ASA product is selected from the group consisting of mesalamine, balsalazide, ipsalazide, olsalazine, sulfasalazine and mixtures thereof.
68. A method of decreasing the probability of an inflammatory mediated mucosal infection in a subject at risk of having an inflammatory mediated mucosal infection, comprising contacting the subject with an effective amount of an anti inflammatory agent and an antiviral agent.
69. The method of claim 68, wherein the inflammatory mediated mucosal infection is caused by a virus.
70. The method of claim 69, wherein the virus is a retrovirus.
71. The method of claim 70, wherein the retrovirus is a lentivirus.
72. The method of claim 71, wherein the lentivirus is an immunodeficiency virus.
73. The method of claim 70, wherein the immunodeficiency virus is selected from the group consisting of human immunodeficiency virus (HIV) type 1, HIVtype 2, and simian immunodeficiency virus (SIV).
74. The method of claim 68, wherein the contacting is in vivo.
75. The method of claim 68, wherein the contacting in vivo is by administering the antiinflammatory agent locally or systemically, prior to, simultaneously with or after administering the antiviral agent.
76. The method of claim 75, wherein the administration is by locally contacting by topical administration.
77. The method of claim 75, wherein the systemic contacting is by intravenous, oral or parenteral administration.
78. The method of claim 68, wherein the subject is a mammal.
79. The method of claim 78, wherein the mammal is a human.
80. The method of claim 68, wherein the antiviral agent inhibits viral fusion or cell entry, viral reverse transcription or nucleic acid replication, viral integration into cell DNA, viral budding or release from a cell, production of infectious virus, or an enzyme associated with viral fusion or infection, reverse transcription or nucleic acid replication, viral integration into cell DNA, viral budding or release from a cell, or production of infectious virus.
81. The method of claim 68, wherein the antiviral agent is a polypeptide or functional mimetic.
82. The method of claim 81 wherein the polypeptide or functional mimetic binds to the virus or a cell surface receptor.
83. The method of claim 81, wherein the polypeptide is a ligand, a viral receptor, an antibody or a fragment thereof.
84. The method of claim 80, wherein the enzyme is a protease, a reverse transcriptase or an integrase.
85. The method of claim 68, wherein the antiviral agent is selected from the group consisting of a protease inhibitor, a nucleoside reverse transcriptase inhibitor, a nonnucleoside reverse transcriptase inhibitor, an integrase inhibitor and mixtures thereof.
86. The method of claim 85, wherein the nucleoside inhibitor is zidovudine (AZT), stavudine (d4T), larnivudine (3TC), didanosine (DDI), zalcitabine (ddC), abacavir and mixtures thereof.
87. The method of claim 85, wherein the nonnucleoside inhibitor is nevirapine, delavirdine, or efavirenz.
88. The method of claim 68, wherein the antiviral agent is a protease inhibitor, a reverse transcriptase inhibitor or an integrase inhibitor.
89. The method of claim 88, wherein the protease inhibitor is saquinavir, ritonavir, indinavir, nelfinavir, or amprenavir.
90. The method of claim 68, wherein the antiinflammatory agent causes a decrease in the recruitment of inflammatory cells, a decrease in the production of chemokines, a decrease in the production of proinflammatory cytokines, or inhibit interaction of a chemokine receptor with its ligand.
91. The method of claim 68, wherein the antiinflammatory agent is selected from the group consisting of an antiinflammatory antibody, an antiinflammatory peptide, an antiinflammatory cytokine, an antiinflammatory chemokine, an antiinflammatory nucleic acid, a steroid, a nonsteroidal antiinflammatory drug, 5ASA products, and combinations thereof.
92. The method of claim 91, wherein the antiinflammatory antibody is selected from the group consisting of an anticytokine antibody, an anticytokine receptor antibody, an antichemokine antibody, an antichemokine receptor antibody, an antiproinflammatory peptide antibody, and combinations thereof.
93. The method of claim 91, wherein the antiinflammatory peptide is selected from the group consisting of an LFA1 antagonist, a cytokine receptor antagonist, a transcription factor, and a soluble TNFa receptor.
94. The method of claim 91, wherein the antiinflammatory cytokine is selected from the group consisting of IL4, IL10, IL13, IL16, and combinations thereof.
95. The method of claim 91, wherein the antiinflammatory nucleic acid is selected from the group consisting of a ribozyme, a nucleic acid encoding an anti inflammatory peptide, an antisense nucleic acid, and combinations thereof.
96. The method of claim 95, wherein the antisense nucleic acid hybridizes to a nucleic acid encoding a cytokine receptor, inflammatory cytokine, a chemokine, or a chemokine receptor.
97. The method of claim 91, wherein the steroid is selected from the group consisting of flunisolide, triamcinoline, triamcinoline acetonide, beclomethasone diproprionate, betamethasone diproprionate, hydrocortisone, cortisone, dexamethasone, budesonide, prednisone, methyl prednisolone, prednisolone, and combinations thereof.
98. The method of claim 91, wherein the nonsteroidal antiinflammatory drug is selected from the group of salicylic acid derivatives consisting of salicylic acid, sodium thiosalicylate, choline salicylate, magnesium salicylate, diflunisal, ibuprofen, naproxen, sulindac, diflunisal, salicylsalicylic acid, choline magnesium trisalicylate, acetylsalicylic acid, salsalate, sodium salicylate and combinations thereof.
99. The method of claim 91, wherein the nonsteroidal antiinflammatory drug is selected from the group consisting of flurbiprofen, fenoprofen, naburnetone, ketoprofen, piroxicam, indomethacin, tolmetin, meclofanamate sodium, mefenamic acid, etodolac, ketorolac tromethamine, diclofenac, oxaprozin, bromfenac sodium, rofecoxib, suprofen, fenbuprofen, fluprofen, thalidomide, evening primrose oil, single isomers thereof and combinations thereof.
100. The method of claim 91, wherein the 5ASA product is selected from the group consisting of mesalamine, balsalazide, ipsalazide, olsalazine, sulfasalazine and mixtures thereof.
101. A method of inhibiting activation of a retrovirus, comprising contacting a cell infected with the virus with an activationinhibiting amount of an anti inflammatory agent, wherein the antiinflammatory agent is distinct from 5 ASA or ASA.
102. The method of claim 101, wherein the antiinflammatory agent is selected from the group consisting of an antiinflammatory antibody, an antiinflammatory peptide, an antiinflammatory cytokine, an antiinflammatory chemokine, an antiinflammatory nucleic acid, a steroid, a nonsteroidal antiinflammatory drug, and combinations thereof.
103. A method for inhibiting an inflammatory mediated infection of mucosal tissue, comprising contacting the tissue with an inhibiting effective amount of an anti inflammatory agent, wherein the antiinflammatory agent is distinct from 5 ASA or ASA.
104. The method of claim 103, wherein the antiinflammatory agent is selected from the group consisting of an antiinflammatory antibody, an antiinflammatory peptide, an antiinflammatory cytokine, an antiinflammatory chemokine, an antiinflammatory nucleic acid, a steroid, a nonsteroidal antiinflammatory drug, and combinations thereof.
105. A method of inhibiting an inflammatory mediated mucosal infection in a subject having or at risk of having an inflammatory mediated mucosal infection, comprising contacting the subject with an effective amount of an anti inflammatory agent, wherein the antiinflammatory agent is distinct from 5 ASA or ASA.
106. The method of claim 105, wherein the antiinflammatory agent is selected from the group consisting of an antiinflammatory antibody, an antiinflammatory peptide, an antiinflammatory cytokine, an antiinflammatory chemokine, an antiinflammatory nucleic acid, a steroid, a nonsteroidal antiinflammatory drug, and combinations thereof.
107. A method of inhibiting progression of an HIVrelated disorder in a subject having a human immunodeficiency virus, comprising administering to the subject having the HIV viral infection a therapeutically effective amount of an antiinflammatory agent that inhibits progression of the HIV virus.
108. The method of claim 107, wherein the antiinflammatory agent is distinct from ASA or 5ASA.
109. The method of claim 107, further comprising administering an antiviral agent.
110. A method for preventing or decreasing the probability of infection of a subject at risk of an HIV infection, comprising administering to the subject a prophylactic effective amount of an antiinflammatory agent which inhibits or decreases the probability of HIV infection of the subject.
111. The method of claim 110, wherein the antiinflammatory agent is distinct from ASA or 5ASA.
112. The method of claim 110, further comprising administering an antiviral agent, prior to, simultaneously with or after administering the antiinflammatory agent.
113. The method of claims 107 or 110, wherein the antiinflammatory agent is administered topically.
114. The method of claims 107 or 110, wherein the antiinflammatory agent is administered systemically.
115. A pharmaceutical composition comprising at least one dose of a therapeutically effective amount of an antiinflammatory agent, in a pharmaceutically acceptable carrier, wherein the dose is in an amount effective to inhibit or decrease the probability of immunodeficiency virus infection.
116. The pharmaceutical composition of claim 115, further comprising an antiviral agent.
117. The pharmaceutical composition of claim 115, further comprising a pharmaceutically acceptable gel, cream, foam or suppository.
118. An article of manufacture, comprising at least one antiinflammatory agent and instructions for use of the agent in treating, preventing or decreasing the probability of an immunodeficiency virus infection.
119. The article of manufacture of claim 118, further comprising an antiviral agent.
120. The article of manufacture of claim 118, wherein the article is selected from the group consisting of a condom, a sponge, a diaphragm, a cervical cap, a vaginal ring, a suppository, and an enema.
121. A method of inhibiting activation of a retrovirus in a tissue infected with the virus, comprising contacting the tissue with an activationinhibiting effective amount of an antiinflammatory agent.
122. The method of claim 121, wherein the antiinflammatory agent is distinct from ASA or 5ASA.
123. The method of claim 121, further comprising contacting the tissue with an antiviral agent prior to, simultaneously with or after administering the anti inflammatory agent.
124. A method for inhibiting activation of a retrovirus in a subject infected with the virus, comprising contacting the subject with an activationinhibiting amount of an antiinflammatory agent.
125. The method of claim 124, wherein the antiinflammatory agent is distinct from ASA or 5ASA.
126. The method of claim 124, further comprising contacting the subject with an antiviral agent prior to, simultaneously with or after administering the anti inflammatory agent.
127. An article of manufacture, comprising at least one antiinflammatory agent and instructions for use of the agent in prophylaxis of immunodeficiency virus infection.
128. The article of manufacture of claim 127, further comprising an antiviral agent.
129. The article of manufacture of claim 127, wherein the article is selected from the group consisting of a condom, a sponge, a diaphragm, a cervical cap, a vaginal ring, a suppository, and an enema.
Description:
INTERNATIONALSEARCHREPORTIntemationalapplicationNo. PCTUS00/13142 C(Continuation).DOCUMENTSCONSIDEREDTOBERELEVANT Category*Citationofdocument,withindication,whereappropriate, oftherelevantpassagesRelevanttoclaimNo. YGOLETTIetal.Theinvitroinductionofhuman1-129 immunodeficiencyvirus(HIV)replicationinpurifiedprotein derivative-positiveHIV-infectedpersonsbyrecallantigenrespons e toMycobacteriumtuberculosisistheresultofabalanceofthe effectsofendogenousinterleukin-2andproinflammatoryand antiinflammatorycytokines.JournalofInfectiousDiseases.May 1998,Vol.177,No.5,pp.1332-1338.Seeentiredocument. YORNSTEINetal.Theantiinflammatoryandantiviraleffectsof1-129 hydroxychloroquineintwopatientswithacquired immunodeficiencysyndromeandactiveinflammatoryarthritis. ArthritisandRheumatism.January1996,Vol.39,No.1,pp. 157-61.Seeentiredocument. YDatabaseMedlineonDialog,AccessionNo.PB0326,IMAIZUMI1-129 etal.EffectoflongtermtherapywithglycyrrhizinforHIV infectioninahemophiliapatient.Int.Conf.AIDS.1994.Vol.10, No.1,pp.224(AbstractNo.PB0326).Seeentiredocument. YDatabaseMedlineonDialog,AccessionNo.60049,BABAetal.1-129 Anti-inflammatoryalkaloidcepharanthineinhibitsHIV-1 replicationinchronicallyinfectedcells.Int.Conf.AIDS.1998, Vol.12,pp.1010(AbstractNo.60049).Seeentiredocument. YBOURINBAIARetal.Potentiationofanti-HIVactivityof1-129 anti-inflammatorydrugs,dexamethasoneandindomethacin,by MAP30,theantiviralagentfrombittermelon.Biochemicaland BiophysicalResearchCommunications.17March1995,Vol. 208,No.2,pp.779-885.Seeentiredocument. INTERNATIONALSEARCHREPORTInternationalapplicationNo. PCT/US00/13142 BoxIObservationswherecertainclaimswerefoundunsearchable(Cont inuationofitem1offirstsheet) Thisintemationalreporthasnotbeenestablishedinrespectofcertai nclaimsunderArticle17(2Xa)forthefollowingreasons: 1. n ClaimsNos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi sAuthority,namely: 2.2 ClaimsNos.: becausetheyrelatetopartsoftheintemationalapplicationthatdono tcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulinternationalsearchcanbecarriedout,s pecifically: 3.2 ClaimsNos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4 (a). BoxIIObservationswhereunityofinventionislacking(Continuation ofitem2offirstsheet) ThisIntemationalSearchingAuthorityfoundmultipleinventionsint hisintemationalapplication,asfollows: PleaseSeeExtraSheet. 1.2 As allrequiredadditionalsearchfeesweretimelypaidbytheapplicant, thisintemationalsearchreportcoversallsearchable u claims. 2.XAsallsearchableclaimscouldbesearchedwithouteffortjustifyi nganadditionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.As ontsomeoftherequiredadditionalsearchfeesweretimelypaidbythea pplicant,thisintemationalsearchreportcovers onlythoseclaimsforwhichfeeswerepaid,specificallyclaimsNos.: 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant .Consequently,thisintemationalsearchreportis restrictedtotheinventionfirstmentionedintheclaims ;itiscoveredbyclaimsNos.: RemarkonProtest1Theadditionalsearchfeeswereaccompaniedbythea pplicant'sprotest. Noprotestaccompaniedthepaymentofadditionalsearchfees. INTERNATIONALSEARCHREPORTIntcrnafion :l application No_ PG'CIUSOO/13142 A.CLA SSIFICAfiONOFSUBJECTMATTES IPC(7): AO1K4}/04;A61K 38/43,39/00.39/395,45/00 BOXn BSERVATlONS WHERE lJNlTYOFINVENTIONWASLACKING ThisIls2.foundmultipleinveations as follows: Thisapllicationeontainsthefollowinginventionsorgroupsof invcntionx whicb arenotsolinkedastoformasingle invention :conceptunderPCTRule13.1. Inorderfornll inventions to be qcarchcd, thc appropriute additionalsearchfees mustbepaid. Group1,alaims L-30,101.102.107-109,113,114,andt21-126,drawnwmethodsandcomp ositionsforinhibitingviml ucti'vatica. GroupE,7 Ca mrß 31-100, 103-106, 110-120 and 121-129, drawntomethodsandcompositions for inhibiting viral iafcctior. TheinvilionslistelasGroupsIandrIdonotrelatetoasingle inventivc conccpt under PCT Rule 13.1becauseunder PCTRut:132,theylackthesameorcormspondiagspecialtechnicalfeut resforthefollowiag ruasoas : Each group has differentmethodanddifremntexpectedoutComcs.