Title:
TREATMENT AND PREVENTION OF IMMUNODEFICIENCY VIRUS INFECTION BY ADMINISTRATION OF NON-PYROGENIC DERIVATIVES OF LIPID A
Document Type and Number:
WIPO Patent Application WO1999015162
Kind Code:
A3
Abstract:
The present inventors have found that certain preparations containing LPS and/or lipid A variants, derivatives, and/or analogs demonstrate non-pyrogenic properties and exhibit anti-viral activities. In particular, non-pyrogenic preparations of LPS, lipid A, LPS antagonists and lipid A antagonists, and derivatives thereof induce beta chemokine secretion, such as MIP-1 beta , but not proinflammatory cytokines, such as TNF alpha , IL-1 beta and IL-6. Non-pyrogenic preparations of the invention have been demonstrated by the Applicant to suppress HIV replication in human peripheral blood monocytes, as described by way of example herein. The present invention provides preparations of LPS or lipid A variants, analogs and derivatives of decreased or absent pyrogenicity which can be used as therapeutics for the treatment or prevention of immunodeficiency virus infection and its consequences.
Inventors:
HONE DAVID M (US)
CROWLEY RICHARD (US)
LEWIS GEORGE (US)
CROWLEY RICHARD (US)
LEWIS GEORGE (US)
Application Number:
PCT/US1998/020264
Publication Date:
May 20, 1999
Filing Date:
September 28, 1998
Export Citation:
Assignee:
UNIV MARYLAND BIOTECH INST (US)
HONE DAVID M (US)
CROWLEY RICHARD (US)
LEWIS GEORGE (US)
HONE DAVID M (US)
CROWLEY RICHARD (US)
LEWIS GEORGE (US)
International Classes:
A61K39/02; A61K45/06; (IPC1-7): A61K31/70
Domestic Patent References:
| WO1995023156A1 | 1995-08-31 | |||
| WO1992000101A1 | 1992-01-09 | |||
| WO1994021292A1 | 1994-09-29 | |||
| WO1992006113A2 | 1992-04-16 | |||
| WO1984004526A1 | 1984-11-22 | |||
| WO1997018837A1 | 1997-05-29 |
Foreign References:
| EP0536969A2 | 1993-04-14 | |||
| EP0437016A2 | 1991-07-17 | |||
| GB2220211A | 1990-01-04 | |||
| EP0668289A1 | 1995-08-23 |
Other References:
H. FRIEDMAN ET AL.: "IMMUNOADJUVANTICITY OF ENDOTOXINS AND NONTOXIC DERIVATIVES FOR NORMAL AND LEUKEMIC IMMUNOCYTES", ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY, vol. 256, 1990, pages 525 - 535, XP002094632
A.G. JOHNSON ET AL.: "CHARACTERIZATION OF A NONTOXIC MONOPHOSPHORYL LIPID A", REVIEWS OF INFECTIOUS DISEASES, vol. 9, no. S5, 1987, pages S512 - S516, XP002094633
A. VERANI ET AL.: "C-C CHEMOKINES RELEASED BY LIPOPOLYSACCHARIDE (LPS)-STIMULATED HUMAN MACROPHAGES SUPPRESS HIV-1 INFECTION IN BOTH MACROPHAGES AND T CELLS", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 185, no. 5, March 1997 (1997-03-01), pages 805 - 816, XP002094634
CHEMICAL ABSTRACTS, vol. 109, no. 19, 7 November 1988, Columbus, Ohio, US; abstract no. 163524, "DISACCHARIDE DERIVATIVES AS ANALGESICS" XP002094635
A.G. JOHNSON ET AL.: "CHARACTERIZATION OF A NONTOXIC MONOPHOSPHORYL LIPID A", REVIEWS OF INFECTIOUS DISEASES, vol. 9, no. S5, 1987, pages S512 - S516, XP002094633
A. VERANI ET AL.: "C-C CHEMOKINES RELEASED BY LIPOPOLYSACCHARIDE (LPS)-STIMULATED HUMAN MACROPHAGES SUPPRESS HIV-1 INFECTION IN BOTH MACROPHAGES AND T CELLS", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 185, no. 5, March 1997 (1997-03-01), pages 805 - 816, XP002094634
CHEMICAL ABSTRACTS, vol. 109, no. 19, 7 November 1988, Columbus, Ohio, US; abstract no. 163524, "DISACCHARIDE DERIVATIVES AS ANALGESICS" XP002094635
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