Title:  Method for treating AIDS and HIV infection using select peptides from the beta subunit of human chorionic gonadotropin

United States Patent:  6,331,610

Assignee:  Metatron, Inc. (Deer Park, NY)

Filed:  August 7, 1997

The present invention relates to select peptides of the carboxy terminal and aminoterminal portion of the beta unit of hCG and pharmaceutically acceptable derivatives thereof that can be used for controlling retroviral, e.g., human immunodeficiency virus (BV infections. The invention comprises a method in vitro as well as in vivo for prevention and/or treatment of acquired immune deficiency syndrome (AIDS) at pharmacological doses of beta hCG-derived peptides and pharmaceutically acceptable derivatives thereof which are sufficient to exert an anti-HIV effect for a sufficient period of time.

SUMMARY OF THE INVENTION

In search of the active element within hCG, more specifically within its beta subunit, it has been discovered unexpectedly by the present inventor that the carboxyterminal portion (CTP) of hCG plays the major role in inhibiting HIV replication. The NH₂ -terminal portion also had an effect, but the hCG core region had practically no effect. This discovery was totally unexpected in as much as the C-terminal and N-terminal portions were believed to be biologically inactive. This discovery was unexpected even to those skilled in the art as only the core region of beta hCG was postulated to have some activity due to its sequence similarity with certain growth hormones such as PDGF and related hormones of the same family. Furthermore, such peptides displayed biological activity despite the fact that they were nonglycosylated. Peptides representing carboxy-terminal portion(s) of beta hCG are known in the art and the U.S. Pat. No. 4,691,006, which is incorporated by reference, discloses some of them.

The present invention, therefore, comprises a method for preventing or inhibiting HIV replication and spread in vitro as well as in vivo using select peptides (peptide fragments) of beta hCG. Such peptides are derived either from the carboxy terminal (hCG-CTP) or amino terminal end of beta hCG, alone or in combination with drugs having anti-HIV activity. The present invention relates to the discovery that a peptide fragment corresponding to amino acids 100-145 of beta hCG and peptide fragments thereof containing at least four amino acid units exhibit unexpected anti-HIV activity. The present invention also relates to the discovery that a peptide fragment corresponding to amino acids 1-50 of beta hCG and peptide fragments containing at least four amino acid units exhibit unexpected anti-HIV activity. Such activities were observed even though the peptides were not glycosylated. Thus, the present invention is directed to the use either of a peptide fragment of at least four amino acids derived from the N-terminal end of beta hCG (witch corresponds to amino acids 1-50) or a peptide fragment of at least four amino acids derived from hCG-CTP (which corresponds to amino acids 100-145 of beta hCG). More preferably, the peptide fragments which are used in the present invention correspond to amino acids 1 to 45 or 106 to 145 of beta hCG or a peptide fragment thereof containing at least four amino acids. In a preferred aspect of the present invention, a five amino acid peptide fragment of the N-terminal end or hCGT-CTP is used to inhibit HIV replication In a more preferred aspect of the present invention, the peptide fragment is at least about 10 amino acid units in size, even more preferably about 20 amino acid units in size and in an even more preferred aspect, the fragment is at least about 40 amino acids units in size. One or more of these peptides is administered in an anti-HIV effective amount to patients who have been infected with HIV in order to inhibit the growth, replication and/or elaboration of HIV and to delay the onset or prevent the occurrence of AIDS in HIV positive patients.

More specifically, the invention comprises a method for suppressing HIV replication and spread by employing therapeutically effective doses of the N-terminal end of hCG or hCG-CTP or peptide fragments thereof containing at least four amino acid units, thereof as active ingredients in pharmaceutical formulations administered by accepted means of drug delivery known in the art, e.g., oral parenteral including intramuscular and intravenous, buccal, transdermal and related routes. of administration. The preferred method of delivery is intravenous or intramuscular delivery in an amount and for a period of time both of which are sufficient to exert an inhibitory effect on HIV replication and spread of HIV with the goal of treating or preventing AIDS.

The invention also comprises a method for preventing the mother-to-fetus (vertica) and sex-borne (horizontal) spread of HIV by employing therapeutically effective doses of N-terminal end peptides or hCG-CTP peptides and derivatives thereof as described hereinabove as active ingredients in pharmaceutical formulations in an amount and for a period of time both of which are sufficient to exert a protective effect against vertical and horizontal transmission of HIV.

Claim 1 of 18 Claims

What is claimed is:

1. A method of treating HIV infection in human cells and tissues or inhibiting the spread of human immunodeficiency virus (HIV) to uninfected human cells and tissues comprising administering to a human host an anti-HIV effective amount of a peptide fragment of amino acids 1-50 or 100-145 of SEQ ID NO:1 of beta human chorionic gonadotropin (hCG) or an anti-HIV fragment thereof containing at least four contiguous amino acid units of said amino acids 1-50 or 100-145 for a time and under conditions effective to reduce HIV infection or spread of HIV to uninfected human cells.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.