Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1997-11-10
2001-08-14
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S002600, C514S885000, C530S350000, C530S351000, C424S617000, C424S618000, C424S649000, C424S085100
Reexamination Certificate
active
06274552
ABSTRACT:
TECHNICAL FIELD
The present invention relates to compositions and methods for delivery of biologically-active factors, such as cytokines, growth factors, chemotherapeutic agents, nucleic acids, therapeutic agents, and other immune products. In addition, the present invention comprises vaccines which are effective in immunizing a human or animal against a biologically-active factor while reducing or eliminating the toxicity of the factor.
BACKGROUND OF THE INVENTION
Various biologically-active factors have been isolated from humans or animals which have been reported to have therapeutic efficacy. These compounds include cytokines and growth factors. However, it has been found that when these various factors are isolated and purified from natural sources or genetically engineered material, and then injected into a human or animal, they often cause severe side effects and exhibit unwanted toxicity. Because of this toxicity, it has been difficult to use the compounds therapeutically. In addition, it has been difficult to use the active compounds as antigens to produce antibodies against the molecules.
Aluminum compounds have been used to form water-insoluble antigenic substances. For example, U.S. Pat. No. 3,577,523, issued to Stolar, et al., discloses the combination of aluminum stannate with antigenic extracts to form water-insoluble slow release antigenic substances. More generally, the Stolar, et al. patent discloses the use of antigenic depot agents incorporating water-insoluble antigenic substances that slowly release active agents that are absorbed without adverse systemic reactions or other adverse side effects.
Metals have also been used in capsular polysaccharide metal complex vaccines. For example, in U.S. Pat. No. 4,740,589, issued to Moreno, a bacterial capsular polysaccharide constituent was complexed with a metal, preferably aluminum or ruthenium, for the prophylaxis and treatment of bacterial diseases. This patent also discloses the formulation of a three component complex which contains a polysaccharide, a metal, and a third constituent of bacterial outer-membrane protein. The '589 patent discloses that the complex contains a weight percentage of lipopolysaccharide “insufficient to produce significant toxic effects”, the weight percentage being generally 1% or less. Finally, the disclosure in the '589 patent application is limited to the use of the complexes for prophylaxis and treatment of bacterial diseases. U.S. Pat. No. 3,269,912, issued to Grase, discloses a depot vaccine comprising a finely divided aluminum oxide, either aluminum oxide or aluminum oxide aerosol having had absorbed thereon at least one antigen derived from a virus, bacteria, or ectotoxoid, dispersed in an aqueous medium. The '912 patent also discloses that the vaccine forms a colloidal dispersion of the individual spherical crystals of aluminum oxide in the solution.
Selected metals have also been used as components of stable adjuvant emulsion compositions. It is known in the art that aluminum, as the monostearate, or in the form of hydrated salts of fatty acids, are emulsifying agents, or stabilizers of the emulsion in the vaccine composition.
However, substantial need exists for a therapeutically effective composition with reduced toxicity, that may be used in therapies for a wide range of immune diseases, cancers, viral diseases and bacterial diseases. In addition, there is a need for a composition that can reduce the toxicity of normally toxic biologically-active compositions so that the compounds can be used as vaccines in the human or animal.
Current therapies for the treatment of diseases and pathological conditions, including genetic diseases, congenital diseases and acquired diseases such as bacterial infections, viral infections, cancer, immune deficiency diseases, autoimmune diseases, psychiatric diseases, cardiovascular diseases, reproductive dysfunction, somatic growth dysfunction, stress related diseases, muscular dystrophy, osteoporosis, ocular diseases, allergies, and transplantation rejection, require administration of toxic doses of biologically-active factors that have widespread effects throughout the body. These therapies are not specifically targeted to the affected organs for direct delivery of a biologically active factor.
Current treatments for cancer include administration of chemotherapeutic agents and other biologically active factors such as cytokines and immune factors. The administration of chemotherapeutic agents to the entire body creates toxic and adverse side effects such as organ damage, loss of senses such as taste and feel, and hair loss. Many chemotherapeutic agents are designed to kill rapidly dividing cells which indescriminately effects the hematopoetic system and the gastrointestinal system leading to changes in blood and immune cells, vomiting, gastric distress and weight loss. Administration of immune factors, such a cytokines, to the entire body system leads to activiation of unwanted immune responses and inhibition of other immune functions. Such therapies provide treatment for the condition, but come with a wide array of side effects that must then be treated. In addition, bolus administration of a drug may not be optimal because of rapid clearance.
Other types of biologically active factors, based on nucleic acids, are being developed for therapeutic use to treat diseases and pathological conditions. Examples of such therapeutic uses include, gene replacement, antisense gene therapy, triplex gene therapy and ribozyme-based therapy. However, to be successful, an effective means for the delivery of the therapeutic agent across cellular, nuclear and microorganismal membranes is required.
The recent advent of technology, and advances in our ability to understand the structure and function of many genes makes it possible to selectively turn off or modify the activity of a given gene. Alteration of gene activity can be accomplished many ways. For example, oligonucleotides that are complementary to certain gene messages or viral sequences, known as “antisense” compounds, have been shown to have an inhibitory effect against viruses. By creating an antisense compound that hybridizes with the targeted RNA message of cells or viruses the translation of the message into protein can be interrupted or prevented. In this fashion gene activity can be modulated.
The ability to deactivate specific genes provides great therapeutic benefits. For example, it is theoretically possible to fight viral diseases with antisense RNA and DNA molecules that seek out and destroy viral gene products. In tissue culture, antisense oligonucleotides have inhibited infections by herpes-viruses, influenza viruses and the human immunodeficiency virus that causes AIDS. It may also be possible to target antisense oligonucleotides against mutated oncogenes. Antisense technology also holds the potential for regulating growth and development. However, in order for the gene therapy to work, antisense therapeutic compounds must be delivered across cellular plasma membranes to the cytosol.
Gene activity is also modified using sense DNA in a technique known as gene therapy. Defective genes are replaced or supplemented by the administration of “good” or normal genes that are not subject to the defect. The administered normal genes which insert into a chromosome, or may be present in extracellular DNA, produce normal RNA, which in turn leads to normal gene product. In this fashion gene defects and deficiencies in the production of gene product may be corrected. Still further gene therapy has the potential to augment the normal genetic complement of a cell. For example, it has been proposed that one way to combat HIV is to introduce into an infected person's T cells a gene that makes the cells resistant to HIV infection. This form of gene therapy is sometimes called “intracellular immunization.” Genetic material such as polynucleotides may be administered to a mammal to elicit an immune response against the gene product of the administered nucleic acid sequence. Such gene v
Paciotti Guilio F.
Tamarkin Lawrence
CytImmune Sciences Inc.
Delacroix-Muirheid C.
Jones Dwayne C.
Kilpatrick & Stockton LLP
LandOfFree
Composition and method for delivery of biologically-active... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Composition and method for delivery of biologically-active..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Composition and method for delivery of biologically-active... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2516807