Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1999-05-21
2004-02-24
Nguyen, Dave T. (Department: 1632)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S002600, C514S021800, C424S529000
Reexamination Certificate
active
06696422
ABSTRACT:
BACKGROUND OF THE INVENTION
I. Field of the Invention
The present invention relates to a method for using Product R as hereinafter defined in combination with other anti-human immunodeficiency virus (HIV) to treat patients having HIV infections.
II. Description of the Related Art
A retrovirus designated human immunodeficiency virus (HIV) is the etiological agent of the complex disease that includes progressive destruction of the immune system (acquired immune deficiency syndrome; AIDS) and degeneration of the central and peripheral nervous system. This virus was previously known as LAV, HTL-III, or ARV. The virus specifically attacks T-4 helper lymphocytes, a subgroup of T-lymphocytes that plays a major role in defending the body against infectious diseases. Depletion of this subset of lymphocytes is manifested by an increased incidence of opportunistic infections like pneumocystis carinii and certain cancers. More specifically, the virus enters the T-lymphocyte and incorporates viral encoded DNA into the DNA of the host T-lymphocyte. As long as the infected T-lymphocyte remains inactivated, the virus will quietly remain in the DNA of the host cell. This will not kill the cell but may impair its function. When the infected T-lymphocytes are activated by stimuli such as a specific antigen, the viral DNA in the host DNA is expressed and produces new viral particles. The host T-lymphocyte is then killed and lysed, releasing new viral particles that can invade and kill other T-lymphocytes. The loss of T-4 lymphocytes is profound and occurs even faster than can be accounted for by direct viral killing of the cells. This has led some investigators to postulate that the infection somehow shuts off the production of T-4 lymphocytes. In any case, the normal thymus is no longer functioning and the killed T-lymphocytes cannot be replaced leaving the patient vulnerable to subsequent infections. Especially striking are recent studies of the thymuses of deceased AIDS patients ranging in age from 10 months to 42 years. AIDS victims have profound thymic involution; much more extensive than in age-matched patients who died of other causes.
The cure of a person with AIDS will probably require one agent to eliminate the virus and other agents to cause the body to replace T cells that have been killed by the virus. The first step is to eliminate the AIDS virus from the patient. This will have to be supported by other therapies to induce restoration of immune function. Studies to date with macrophage activating agents, interferon inducers and lymphokines have been disappointing, possibly because their targets, T-lymphocytes, do not exist in sufficient numbers. Interleukin 2 restores the function of one subset of non T-cells (natural killer cells) but has no effect on a host of other serious defects. More drastic measures can be performed. One potential method of restoring the immune system is by transplanting bone marrow from healthy donors. However, this is a dangerous procedure. It may produce lethal graft versus host disease unless the patient's donor is an identical twin.
A common feature of retrovirus replication is the extensive post-translational processing of precursor polypeptides by a vitally encoded protease to generate mature vital proteins required for virus assembly and function. Inhibition of this processing prevents the production of normally infectious virus. It has been demonstrated that genetic inactivation of the HIV encoded protease resulted in the production of immature, non-infectious virus particles. These results indicate that inhibition of the HIV protease represents a viable method for the treatment of AIDS and the prevention or treatment of infection by HIV. However, administration of a HIV protease inhibitor sometimes cause side effects including nausea, nephrolithiasis, increased bilirubin, or gastro-intestinal upset.
Zidovudine (AZT) is a synthetic pyrimidine analog that differs from thymidine in having an azido substituent instead of a hydroxyl group at the 3′ position of the deoxyribose ring. It was initially developed as an anticancer agent and subsequently found to inhibit the reverse transcriptase (RT) of Friend leukemia virus. Soon after the identification of a human retrovirus as the etiologic agent of AIDS, zidovudine was shown to have anti-HIV activity in vitro. Zidovudine selectivity is due to the preferential interaction of AZT-TP with the RT. Phosphorylation of zidovudine to its active form, AZT-TP, is accomplished by cellular enzymes. Zidovudine is an efficient substrate for the cellular thymidine kinase which converts it to AZT-MP in both infected and uninfected cells. AZT-MP accumulates in cells because of slow phosphorylation to AZT-DP by host-cell thymidylate kinase which is the rate-limiting step in AZT-TP formation. AZT-MP is a competitive inhibitor or thymidylate kinase and reduces the conversion of dTMP to dTDP which leads to decreased formation of dTTP. Other nucleoside analogs including ddI, ddC and ddA also have activity against HIV through a similar mechanism to that described for AZT.
However, the major toxicity of zidovudine is on the bone marrow, with macrocytic anemia and granulocytopenia common occurrences. The mechanisms of these toxic effects are uncertain. Rare instances of pancytopenia with hypocellular marrow have been described, and patients with poor bone marrow reserve, secondary to opportunistic infections or vitamin B
12
deficiency, have more toxicity than patients with sufficient marrow reserve. Nausea, myalgia, insomnia, fever, rash, nail pigmentation, and severe headaches may also be observed.
Reticulose
1
emerged as an antiviral product in the 1930's. While it was originally believed to be a product composed of peptone, peptides and nucleic acids, the precise composition remains unidentified. Nevertheless, Reticulose has demonstrated an ability to inhibit rapidly the course of several viral diseases. It is nontoxic, miscible with tissue fluids and blood sera and free from anaphylactogenic properties. Product R is a refinement of the original Reticulose prepared by an improved manufacturing process. It is a peptide nucleic acid preparation with a defined composition. Recent studies demonstrated that Product R can also stimulate the immune system and red blood cell production, suggesting that Product R is an immune system modulator.
1. Reticulose is a trademark of Advanced Viral Research Corp.
Insofar as the applicant knows, Product R has never been used, nor suggested for treating AIDS patients in combination with other anti-AIDS agents. It is now discovered that a combination of Product R and other antiviral agents useful for treating HIV infections or AIDS presents an advantageous treatment for AIDS patients.
Most infectious diseases caused by bacteria antimicrobialgents (antibiotics) are administered to attack a metabolic pathway in the invading bacteria so as to rapidly decrease the inoculum size of the infecting organism (the number of bacteria). The decrease in the inoculum size of the infecting bacterium allows the immune system to come in and mop up, that is, remove the last vestiges of the infecting organism. Therefore, a functioning immune system is vital for treatment of most infectious diseases.
One way of treating patients infected with HIV, as shown in the present application, is to quickly decrease the viral load by administering nucleoside analogues, for example, azidothymidine and lamivudine, together with a protease inhibitor to quickly decrease the viral load by attacking the replicative pathway of the virus directly, while administering Product R to stimulate both the bone marrow and cytocidal arm of the immune system. When the viral load has reached zero or reaches a low plateau the nucleoside analogues and the protease inhibitor are discontinued and the patient is continued on Product R therapy alone. This removes the potential side effects of the nucleoside analogues and protease inhibitor including the inhibiting immune function. On Product R therapy alone, now faced with a viral l
Advanced Viral Research Corp.
Cohen & Pontani, Lieberman & Pavane
Nguyen Dave T.
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