Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1998-03-16
2003-07-22
Swartz, Rodney P (Department: 1645)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C435S007100, C528S338000, C528S340000
Reexamination Certificate
active
06596701
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a new paradigm of disease centering around the metabolic pathways of S-adenosyl-L-methionine (SAM), the intermediates of these pathways and other metabolic pathways influenced by the SAM pathways. Specifically, the invention relates to analyzing and regulating SAM pathways that exist in association with a disease or condition including cancer and a number of diseases or conditions connected with degeneration and aging. More specifically, the invention concerns designing analytical, diagnostic and therapeutic protocols and agents for such disease states and conditions through recognition of the central role of SAM and its metabolic pathways in controlling cell metabolism, cell growth and intercellular communication.
2. Description of the Background Art
It is commonly believed that an understanding of cellular metabolism and function, as well as the nature of biological degeneration and the creation of disease conditions, can be achieved by ascertaining the genetic information contained in eukaryotic cells and understanding how this genetic information is transcribed and translated into proteins which then control chemical conversions within the cell. The present conceptual frame work considers DNA as the core of life. Within this framework, the function of proteins is commonly assumed to be regulated in large part by phosphorylation and dephosphorylation of relevant proteins at appropriate times.
The present invention was made in response to the absence of a greater unifying relationship between small molecule biochemistry and the macromolecules RNA, DNA and protein. Present-day molecular biology is focused completely on macromolecules and has provided essentially no connection with the small molecules which carry out the chemical reactions of life. In fact, the study of small molecules in the biological and biochemical sciences has not been in vogue for the last 20 years.
The present inventors have recognized that the focus of the present paradigm for metabolic management are at best very incomplete. Such a recognition demands a “paradigm shift” of the sort described by Thomas Kuhn in
The Structure of Scientific Revolutions
(2nd ed., University of Chicago Press (1970)). The prevailing view will change completely when a single paradigm shift is made which defines the conceptual basis for the present invention. This paradigm shift is to the view of the present invention, that life is regulated by S-adenosyl-L-methionine (SAM) through at least eight “donor/cleavage” pathways. In addition, as conceived by the present inventors, significant regulation occurs at the RNA level as opposed to the DNA level.
It is proposed here that our present state of knowledge and interpretation of disease has evolved into two classes which are termed by the present inventors: (1) “exogenous disease”, for example that caused by viruses, bacteria and organisms exogenous to the affected subject, and (2) “endogenous disease”, such as cancer and arthritis, largely associated with internal changes in the affected subject and frequently associated with aging. At present, understanding of exogenous disease is greater due to our knowledge of the external and identifiable causative agents. This knowledge has provided diagnostic and therapeutic procedures which are quite effective against many pathological states, such as bacterial infections. Comparatively speaking, we understand surprisingly little about endogenous diseases. While an enormous body of facts surrounding most endogenous diseases exists, we unfortunately have minimal molecular understanding of their etiology. The reason for this is simple: we have been adhering to the wrong paradigm, a DNA-centered conceptual framework which does not include regulation through RNA or through the eight pathways of SAM.
With the new view of life in accordance with the paradigm shift described herein, the diseases of man can be understood from an entirely new perspective. Most importantly, and practically, from this novel view of life and biochemical processes, the present invention suggests ways to discover and implement new diagnostics and therapeutics for virtually every endogenous disease of man, as well as many exogenous diseases such as bacterial and viral infections.
The recognition of the centrality of the eight “donor/cleavage” pathways of SAM by the present inventors and their application to disease will radically alter the existing paradigm since SAM merges the biochemistry of small molecules with that of macromolecules. In order to design methods to assess the overall metabolic state of a eukaryotic organism and to modulate this state in response to a disease or a dysfunctional condition, the central role of SAM in controlling a host of biochemical reactions must be recognized and employed.
A number of publications which describe SAM and SAM metabolism are delineated below.
Several U.S. patents describe SAM, its activity, and various metabolites and utilities thereof U.S. Pat. No. 4,369,177 discloses a stable composition of SAM which includes a salt of SAM in a pharmaceutically acceptable water-soluble salt of a bivalent or trivalent metal. SAM is said to have pharmaceutical effects in various disorders including adipohepatica, hyperlipemia, arteriosclerosis, depression, arthritis deformans, pains in some neurological manifestations and sleeplessness.
U.S. Pat. No. 4,956,173 discloses use of ademethionine (a common name for a SAM salt) for the preparation of pharmaceutical or cosmetic compositions for counteracting aging of the skin. Ademethionine is said to be a physiological molecule of virtually ubiquitous distribution in the tissues and liquids of the organism where it is involved in important biological processes as a donor of methyl groups in numerous transmethylation reactions and as a precursor of physiological sulfur compounds such as glutathione, cysteine, taurine and CoA. Levels of SAM are known to be high in children and adolescents whereas they are lower in adults and subsequently decrease in presenility and senility. SAM is the active principle of drugs used especially for the treatment of degenerative osteoarthropathy where it has an important role through its antiphlogistic and analgesic activity due to its intervention in the metabolism of arachidonic acid and prostaglandins. Ademethionine is also indicated in the treatment of depressive syndromes.
U.S. Pat. No. 4,764,603 discloses SAM salts with water-soluble polyanions such as polyphosphates, polyvinylsulfonates, sulfates or phosphates, polyacrylates, polystyrene sulfonates.
U.S. Pat. No. 5,073,546 discloses liposoluble salts of SAM with acyl derivatives of taurine. This reference lists a number of important biochemical functions of SAM and summarizes various pharmacologic effects of SAM in test models and the use in clinical pathologies.
U.S. Pat. No. 4,605,625 discloses production of S-adenosyl-L-homocysteine (SAH) by contacting adenosine with D-homocysteine in an aqueous medium in the presence of Pseudomonas cells having the ability to racemize D-homocysteine to D-L-homocysteine and in the presence of SAH hydrolase to synthesize SAH. SAH is said to be an important biologically active substance formed by a methyl group donating reaction in vivo involving SAM. SAH was said to be efficacious as a sedative and a sleep-inducing agent.
U.S. Pat. No. 4,562,149 discloses yeast cultures containing SAM in high concentrations and a process for producing SAM by cultivating the yeast in a liquid culture medium containing methionine.
U.S. Pat. No. 4,242,505 discloses stabilized SAM compositions a sulfuric acid equivalent and a nucleoside sulfate. U.S. Pat. No. 4,057,686 discloses stable sulfonic acid salt of SAM.
U.S. Pat. No. 4,028,183 discloses preparation of double salts of SAM by the action of the enzyme ATP-methionine-adenosyl-transferase on a mixture of ATP and methionine. U.S. Pat. No. 3,954,726 discloses double salts of SAM with sulfuric acid and p-toluene sulfonic acid.
U.S. Pat. No. 3,962,034 discloses pr
O'Day Christine L.
Schwartz Dennis E.
Vermeulen Nicolaas M. J.
MediQuest Therapeutics, Inc.
Morrison & Foerster / LLP
Swartz Rodney P
LandOfFree
S-adenosyl methionine regulation of metabolic pathways and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with S-adenosyl methionine regulation of metabolic pathways and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and S-adenosyl methionine regulation of metabolic pathways and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3027649