Use of lipid conjugates in the treatment of disease

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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C514S053000, C514S054000, C514S056000, C514S061000, C514S062000, C536S018700, C536S020000, C536S021000, C536S022100, C536S029100, C536S029130, C536S123100, C536S123130

Reexamination Certificate

active

07034006

ABSTRACT:
The invention provides novel methods for treating disease based upon the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and (tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels. The surprisingly manifold pharmacological properties of the PL-conjugates allow for the invention, disclosed herein, of novel methods for the treatment of a diverse range of disease states, including obstructive respiratory disease, including asthma; colitis and Crohn's disease; central nervous system insult, including blood brain barrier compromise, ischemic stroke, and multiple sclerosis; contact dermatitis; psoriasis; cardiovascular disease, including ischemic conditions and prophylaxis for invasive vascular procedures; cellular proliferative disorders, including anti-tumor vasculogenesis, invasiveness, and metastases; anti-oxidant therapy; hemolytic syndromes; sepsis; acute respiratory distress syndrome; tissue transplant rejection syndromes; autoimmune disease; viral infection; and hypersensitivity conjunctivitis. The therapeutic methods of the invention include administration of phosphatidylethanolamine bound to carboxymethylcellulose, heparin, hyaluronic acid, polyethylene glycol, and hemaccel. Disclosed herein are also new compounds comprised of phospholipid moieties bound to low molecular weight monomers and dimers, including mono- and disaccharides, carboxylated disaccharides, mono- and dicarboxylic acids, salicylates, bile acids, and fatty acids.

REFERENCES:
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Inhibition of LPS-induced chemokine production in human lund endothelial cells by lipid conjugates achored to the membrane Beck, G. Ch, Yard B.A. Schulte J., Oberacker. R, Van Ackern K, Van Der Woude F.J, Krimsky M, Kaszkin M and Yedgar Y.; British Journal of Pharmacology (2002) 135, 1665-1674.
Control of capillary formation by membrane-anchored extracellular Inhibitor of phospholipase A2; Chem, W.M, Soria J, Coria C, Krimsky M and Yedgar S.; FEBS 26215 letters 522 (2002) 113-118.
Interaction of hyacluronic acid-linked phophatidylethonolmine (HyPE) with LDL and its effect on the susceptibility of LDL lips to oxidation; Schnitzer Edit, Dagan Arie, Krimsky Miron, Lichtenberg Dov, Pinchuk Ilya, Shinar Hadassa, Yedgar Saul; CPL 104 (2000) 149-160.
Inhibition of phopholipase A2 as a therapeutic target; Yedgar Saul, Lichtenberg Dov, Schnitzer Edit, BBA Biochimica et Biophyscia Acta 1488 (2000) 182-187.
Modulation of IFN-GAMMA-induced immunogenicity by phosphatidylethanolamine-linked hyaluronic acid; Yard Benito A., Yedgar Saul, Scheele Martin, Van Der Woulde Diane, Beck Grietje, Heidrich Barbel, Krimsky Miron,. Van Der Woulde Fokko J, and Post Stefan TRANSPLANTATION vol. 73, 984-992, No. 6, Mar. 27, 2002.

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