U.S. Patent Documents
2012/0289589November 2012Travis
Other References
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Primary Examiner: Chandrakumar; Nizal
Attorney, Agent or Firm:Novak Druce Connolly Bove + Quigg LLP
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part of U.S. patent application Ser. No. 11/978,318, filed Oct. 29, 2007 now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 11/327,693 (now Abandoned), filed on Jan. 5, 2006, which is a continuation of U.S. patent application Ser. No. 10/328,242 (now U.S. Pat. No. 7,105,685), filed Dec. 22, 2002, which is a continuation of application Ser. No. 09/928,683 (now U.S. Pat. No. 6,566,560) filed on Aug. 13, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/533,386 (now. U.S. Pat. No. 6,274,635) filed on Mar. 22, 2000, which claims priority to U.S. provisional patent application Nos. 60/125,674 and 60/151,595 filed on Mar. 22, 1999 and Aug. 30, 1999, respectively.
Claims
I claim:
1. A method of treatment of Human Immunodeficiency Virus (HIV) by administering to a subject in need thereof a composition comprising a cannabinoid derivative, wherein said cannabinoid derivative is (6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-t- etrahydrobenzo[c]chromene (L-759633) having the formula: ##STR00029##
2. A method of treating diseases of immune dysfunction which are a result of infectious origin comprising Human Immunodeficiency Virus (HIV), or influenza virus (Type A and B) infections using said cannabinoid derivative of claim 1.
3. The use of the cannabinoid derivative of claim 1 in preparing a medicament for treating a disease selected from the group consisting of: HIV, feline immunodeficiency virus (FIV) and simian immunodeficiency virus (SIV) disease, comprising incorporating the cannabinoid derivative of claim 1 into a pharmaceutically acceptable composition comprising a carrier, wherein the cannabinoid derivative of claim 1 is in an amount effective for indirect inhibition of viral replication through attenuation of an immune response which deprives the virus of the signals required by the virus and disrupts the pathways required by the virus for replication, resulting in slowing the progression of said disease.
4. The use of the cannabinoid derivative of claim 1 in preparing a medicament for treatment of a disease selected from the group consisting of: HIV, SIV and FIV disease, comprising incorporating the cannabinoid derivative of claim 1 into a pharmaceutically acceptable composition comprising a carrier and formulating the composition for vaginal or systemic delivery, wherein the cannabinoid derivative of claim 1 is in an amount effective for improving barrier function of vaginal mucosa by strengthening the integrity of tight junctions which bind vaginal epithelial cells together, by increasing the number of layers of the cells, and by disruption of the immune response required by the viruses for transmission as mediated through constitutive expression of CB2 receptors on vaginal epithelial cells and interaction of the CB2 receptors with immune cells.
5. A method of treating transmission of Human Immunodeficiency Virus (HIV) by administering to a subject in need thereof a composition comprising a cannabinoid derivative, wherein said cannabinoid derivative is (6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10- a-tetrahydrobenzo[c]chromene (L-759633) having the formula: ##STR00030##
6. The method of claim 5, wherein the composition is administered to mucosal tissue in an amount effective for retarding uptake of the HIV through the mucosal tissue.
7. The method of claim 6, wherein the mucosal tissue is vaginal mucosal tissue and the composition is administered systemically or topically to the vagina.
Description
BACKGROUND OF THE INVENTION
The retroviral Human Immunodeficiency Viruses (HIV) 1 and 2 are the most common causative agents of AIDS. Through a portion of a viral envelope protein (gp120), HIV binds specifically and with high affinity to the CD4 molecule on T-lymphocytes. Following binding, the virus fuses with the cell membrane and is internalized. Within the cell, it produces a reverse transcriptase which transcribes its genomic RNA to DNA. The reverse HIV transcript is then integrated into the cellular DNA where it exists for the life of the cell as a "provirus." The provirus can remain latent for an indefinite period of time, or it can be "activated" to transcribe mRNA and genomic RNA, leading to protein synthesis, assembly, new virion formation, budding of virus from the cell surface, and cell death.
While the precise events triggering activation are poorly understood, they appear to lead to liberation or production of endogenous cellular factors that interact with the HIV genome to promote translation. In this regard, binding of cellular SP1 to the HIV promoter (which contains several tandem SP1 consensus binding sites) is needed for high-level transcription of the latent HIV genome. Additionally, NF.kappa.B functions as a potent transcriptional activator when it binds to one or two (depending on the HIV strain) consensus binding sites in the HIV enhancer, which is adjacent to the promoter. The transcription factors CREB/ATF, NF-AT, and AP1 also potentiate HIV transcription. As for all retroviruses, the structural and enzymatic gag, pol and env gene products are produced when the provirus is activated. HIV first transcribes gag-pol as a fusion protein which is ultimately cleaved by the HIV protease enzyme to yield the (nature viral proteins. HIV also employs additional regulatory proteins (specifically the tat and rev gene products) as transcriptional enhancers to induce high levels of gene expression. Nef is another HIV gene that modulates viral replication levels.
While the set of factors triggering active viral replication remains only partially understood, some of them include heat shock, ultraviolet radiation, regulatory proteins of other (e.g., superinfecting) viruses, inflammatory cytokines (e.g., IL1, IL2, IL4, IL6, IL10, Tumor Necrosis Factor a (TNF.alpha.), Platelet Activating Factor, Interferon y (IFN.gamma.)), and Nitric Oxide. Many of these factors are T-cell activators (e.g., they precipitate cell cycling and clonal expansion of T-cell populations), and they are released by many B-cells in direct response to infectious agents (such as HIV). Such factors also trigger intracellular signaling events promoting the production of NF.kappa.B and its dissociation from its inhibitor (IkB). Active NF.kappa.B is a DNA binding protein activating the transcription of many cellular genes, and also the HIV genome. In this regard, cytokines such as TNF .alpha. and IL-1 augment NF.kappa.B activity in cultured T-cells.
Some cells harboring the provirus express HIV gp41, gp120