Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
2000-08-25
2003-11-25
Housel, James (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C424S277100, C424S278100, C514S002600, C530S350000, C530S370000
Reexamination Certificate
active
06652861
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to anti-HIV and anti-tumor peptides and polypeptides, as well as to peptides and polypeptides which prevent infection.
2. Description of the Related Art
Anti-HIV and anti-tumor proteins MAP30 (Momordica Anti-HIV Protein 30 kDa) and GAP31 (Gelonium Anti-HIV Protein 31 kDa) have been isolated from
Momordica charanita
and
Gelonium multiflorum
, also known as bitter melon and Himalayan fruit, respectively (Lee-Huang et al., 1990; Lee-Huang et al., 1991; U.S. Pat. Nos. 5,317,009 and 5,484,889). These medicinal plants are given orally in traditional herbal medicine. Thus the bioavailable form of these agents may be peptide fragments from proteolytic cleavage.
MAP30 and GAP31 possess multiple therapeutic targets at different stages of the HIV-1 life cycle. They act on both viral and cellular levels that may be critical to their antiviral and anti-tumor actions. The viral targets include HIV-1 integrase (Lee-Huang et al., 1995), HIV-LTR (Huang et al., 1992), v-cyclin D, v-IL6, and v-FLIP (Li et al., 1998). The cellular targets are caspases (Li et al., 1998), HER2 (Lee-Huang et al., 1999), and ribosome inactivation by N-glycosidase at A2324 of the 28S rRNA (Lee-Huang et al., 1990 and Lee-Huang et al., 1991).
While transmission of HIV can be prevented by using physical barriers during sexual intercourse, physical barriers such as condoms are not completely effective, particularly if there is a defect in the barrier which permits the virus to cross the physical barrier. Additionally, there are situations in which one party is HIV positive but there is a desire to conceive. In this type of situation a physical barrier is useless, as the physical barrier will prevent conception as well as prevent transfer of the virus form one party to the other.
Commercially available compounds for killing the human immunodeficiency virus are also spermicidal. Unfortunately, there has not beet available a method to prevent transmission of HIV while not preventing conception.
Citation of any document herein is not intended as an admission that such document is pertinent prior art, or considered material to the patent ability of any claim of the present application. Any statement as to content or a date of any document is based on the information available to applicant at the time of filing and does not constitute an admission as to the correctness of such a statement.
SUMMARY OF THE INVENTION
The present invention provides a truncated MAP30 or GAP31 protein, which is a peptide or polypeptide and which has the anti-viral and anti-tumor activities of MAP30 and GAP31 but also unexpectedly and advantageously lacks the ribosome inactivation activity that is present in native MAP30 and GAP31 protein. Moreover, this protein has been found to inhibit transmission of HIV, and it is not spermicidal. The present invention also provides for a derivative of the truncated MAP30 or GAP31 protein and a composition containing the truncated MAP30 protein, the truncated GAP31 protein, or a derivative thereof.
Further provided by the present invention are an isolated DNA molecule which encodes for the truncated MAP30 protein or truncated GAP31 protein, a transformed host cell, and a method for producing the truncated MAP30 protein or truncated GAP31 protein.
REFERENCES:
patent: 5484889 (1996-01-01), Lee-Huang et al.
Lee-Huang et al. 1990. MAP 30: a new inhibitor of HIV-1 infection and replication. FEBS vol. 272(12): 12-18.*
Tumer et al. C-terminal deletion mutant of pokeweed antiviral protein inhibits viral infection but does not depurinate host ribosomes. PNAS. vol. 94, pp. 3866-3871.*
Lee-Huang, et al, TAP 29: An anti-human immunodeficiency virus protein fromTrichosanthes kirikowilthat is nontoxic to intact cells, Proc. Natl. Acad. Sci. USA, 1991, 88, 6570-6574.
Lee-Huang, et al., Plant Proteins with Antiviral Activity Against Human Immunodeficiency Virus, Natural Products as Antiviral Agents, 1992, 153-170, Edited by C.K. Chu and H.G. Culter, Plenum Press, New York.
Lee-Huang, et al., Human immunodeficiency virus type 1 (HIV-1) inhibition, DNA-binding, RNA-binding, and ribosome inactivation activities in the N-terminal segments of the plant anti-HIV protein GAP31, Proc. Natl. Acad. Sci. USA, 1994, 91, 12208-12212.
Lee-Huang, et al., Inhibition of the integrase of human immunodeficiency virus (HIV) type ! By anti-HIV plant proteins MAP30 and GAP31, Proc. Natl. Acad. Sci. USA, 1995, 92, 8818-8822.
Browdy and Neimark PLLC
Foley Shanon
Housel James
New York University
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