Methods and compositions for impairing multiplication of HIV-1

a technology of compositions and compositions, applied in the field of methods and compositions for impairing the multiplication of hiv1, can solve the problems of nullifying the proposed mechanism of action for therapeutic benefit in hiv infection, rendering the cells susceptible to infection by the virus, etc., to reduce the viral multiplication, impair the multiplication of the virus, and reduce the viral level of hiv-1.

Inactive Publication Date: 2005-11-03
GOLDSTEIN GIDEON
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0022] In yet a further aspect of the invention, a method for reducing the viral levels of HIV-1 involves exposing a human or other primate to antibody-inducing pharmaceutical compositions described above, actively inducing antibodies that react with most HIV-1 Tat proteins, and impairing the multiplication of the virus in vivo. This method is ap...

Problems solved by technology

Tat renders the cells susceptible to infection by the virus.
However, the specification also shows that these reagents do not block uptake of...

Method used

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  • Methods and compositions for impairing multiplication of HIV-1
  • Methods and compositions for impairing multiplication of HIV-1
  • Methods and compositions for impairing multiplication of HIV-1

Examples

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example 1

Immunological Studies on Minimal Tat Protein Amino Acid Sequences Necessary for Binding to Antibody for Primate-Recognized Epitope I in HIV-1 Tat Protein, Sequence Variations, and Immunological Cross-Reactivities of Antiserums to these Sequences

[0136] A. Synthetic Peptide and Conjugates

[0137] The synthetic peptides were synthesized by solid phase synthesis on derivatized polyethylene supports (R. M. Valerio et al, Int. J. Peptide Res., 44:158-165 (1994)). Immunizing peptides were synthesized with an amino terminal Cys being incorporated to facilitate coupling to a carrier protein and an amidated C-terminus. Detector peptides were synthesized with an amino terminal biotin-Ser-Gly-Ser-Gly- sequence (SEQ ID NO: 27) and a free acid function at the C-terminus for use in ELISA assays for detection of reactivity and cross-reactivity. Immunizing peptides, covalently conjugated to diphtheria toxoid (DT) carrier protein via the cysteinyl side chain, with a peptide-carrier ratio of 5-8 (A. C...

example 2

Immunological Studies on Minimal Tat Protein Amino Acid Sequences Necessary for Binding to Antibody for Primate-Recognized Epitope II in HIV-1 Tat Protein, Sequence Variations, and Immunological Cross-Reactivities of Antiserums to these Sequences

[0155] Using the same procedures outlined in Example 1, the incidence of amino acid sequence variation for 294 B clade and 56 non-B lade HIV-1 Tat sequences was determined within the Epitope II boundaries of antibody binding in monkeys. The results are reported in Tables VII and VIII. The top lines of the tables contain the consensus sequence. The middle lines contain the percent incidence of amino acids found in greater than 5% of sequences at each position, if multiple. The bottom line shows the total incidence including amino acids occurring in greater than 5% of sequences, if multiple. The amino acid variants at Tat position 42 were antigenically cross-reactive.

TABLE VIIEpitope II- 294 B cladesLys41Gly42Leu43Gly44Ile45Ser46Tyr47Gly48A...

example 3

Development of Human Monoclonal Antibody Treatment for Asymptomatic HIV-1 Infections

[0159] Commercially available antibody humanized mice are immunized with a suitable amount of the Epitope II immunogen: Cys-Gly-Ser-Lys-Gly-Leu-Gly-Ile-Ser-Tyr-Gly-Arg-Lys-amide (SEQ ID NO:34) coupled to diphtheria toxoid carrier protein. Hybridomas are screened on biotin- Ser-Gly-Ser-Gly-Leu-Gly-Ile-Ser-Tyr-Gly-Arg-Lys-OH (SEQ ID NO: 35) on streptavidin-coated plates, and an IgG monoclonal antibody with subnanomolar binding affinity and no binding to complement receptors is selected. Specificity is confirmed on recombinant HIV-1 Tat protein.

[0160] Since the monoclonal antibody is directed to a non-self antigen, a conventional pre-clinical production, purification and safety testing is anticipated. Human monoclonal antibodies have a half-life of 20 days in man vs. the 18 hours half-life of OKT3, a mouse monoclonal antibody which is extensively consumed on internal CD3. Daily doses of 5 mg OKT3 main...

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Abstract

A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y7-Leu-X9-Pro-Trp-Z12-R2 (SEQ ID NO: 8). In this composition, at least one of the two variants contains Arg at Y7 and Lys at Z12, and in at least a second of the two variants Y7 is Asn and Z12 is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 323,013, filed Dec. 19, 2002, which is a continuation of U.S. patent application Ser. No. 10 / 114,176, filed Apr. 2, 2002, now U.S. Pat. No. 6,524,582, which is a divisional of U.S. patent application Ser. No. 09 / 561,366, filed Apr. 28, 2000, now U.S. Pat. No. 6,399,067, issued Jun. 4, 2002.BACKGROUND OF THE INVENTION [0002] The present invention relates generally to compositions and methods useful for inhibiting the multiplication of human immunodeficiency virus-1 (HIV-1) in infected patients, symptomatic or asymptomatic, and for attenuating HIV-1 multiplication following primary infection in previously uninfected subjects, thus minimizing progression to AIDS. [0003] A variety of approaches to the treatment of human immunodeficiency virus type 1 (HIV-1) have focused on the transactivating (tat) gene of HIV-1, which produces a protein (Tat) essential for transcript...

Claims

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Application Information

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IPC IPC(8): G01N33/50A61K35/76A61K38/00A61K38/08A61K38/10A61K39/00A61K39/395A61K48/00A61P31/18C07K7/06C07K7/08C07K14/00C07K14/16C07K16/08C07K16/10C07K19/00C12N1/15C12N1/19C12N1/21C12N5/10C12N15/09C12P21/08G01N33/15G01N33/53G01N33/566G01N33/569
CPCA61K38/08G01N2469/20A61K2039/505A61K2039/6037A61K2039/6043C07K7/06C07K14/005C07K16/1045C07K16/1072C07K2317/21C07K2317/34C12N2740/16322G01N33/56988G01N2333/163A61K39/00A61P31/18
Inventor GOLDSTEIN, GIDEON
Owner GOLDSTEIN GIDEON
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