Syntex (u.s.a.) Inc.

Alavita Pharmaceuticals, Inc.

Other

Surromed, Inc.

Alavita Pharmaccuticals, Inc.

Alavita, Inc.

Phytopharm (na) N.v.

Dawa Incorporated

Anthony C Allison

Elsie M Eugui

Peter H Nelson

William A Lee

Chee-Liang L Gu

Noelene E Byars

Joseph M Muchowski

Philip L Felgner

Deborah M Lidgate

Sandu Pitaru

Cherng-chyi Fu

Alain B Schreiber

Vera Morhenn

Marthinus J Van Der Merwe

Petrus B Kruger

Carl F De Vos Albrecht

Marvin P Masada

A Sampath Narayanan

John S Kenney

Roy C Page

Linda C Foster

Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage, enhancing the survivability of platelets during storage or transfusion and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage. In addition, the modified annexin prevents lipid loss from platelets during storage.

Modified annexin compositions and methods of using same

Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage, enhancing the survivability of platelets during storage or transfusion and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothrombinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage. In addition, the modified annexin prevents lipid loss from platelets during storage.

Attenuation of reperfusion injury

Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage.

Modified annexin proteins and methods for their use in organ transplantation

A modified annexin protein, preferably annexin V, is used to prevent thrombosis without increasing hemorrhage. Annexin binds to phosphatidylserine on the outer surface of cell membranes, thereby preventing binding of the prothrombinase complex necessary for thrombus formation. It does not, however, affect platelet aggregation necessary for hemostasis. The modified annexin molecule can be a homodimer of annexin, an annexin molecule coupled to one or more polyethylene glycol chains, or an annexin molecule coupled to another protein. By increasing the molecular weight of annexin, the modified annexin is made to remain in circulation for sufficient time to provide a sustained therapeutic effect.

Modified annexin proteins, and methods and compositions for using them

A method is described for inducing the formation of cementum and a periodontal ligament between a dental implant and bone by administering cementum attachment protein (CAP) together with a calcineurin inhibitor such as cyclosporin A (CSA). Also contemplated is an implant kit comprising a titanium or other biologically inert dental or orthopedic implant and a coating of CAP and a calcineurin inhibitor such as CSA. Furthermore, application of CAP and CSA to dental root surfaces can be used to induce the regeneration of a periodontal ligament during treatment for periodontal disease. A similar method for reattaching a fibrous structure, such as a tendon, ligament or joint capsule, to bone is described.

Combined use of cementum attachment protein and cyclosporin a for improved attachment of dental and orthopedic implants

Sickle-cell diseases are treated with annexin proteins that are modified to increase their half-life in the circulation.

Modified annexin proteins and methods for treating vaso-occlusive sickle-cell disease

Modified annexin proteins and methods for preventing thrombosis

Disclosed is a method of inhibiting hepatitis B infection by administering a therapeutically effective amount of a compound having the formula (Formula 1): ##STR1## wherein R1 is selected from the group consisting of H, lower alkanoyl, lower arylalkylacyl, arylacyl, and C-1-linked saccharide, and R2 is separately selected from the group consisting of H, lower alkyl, lower arylalkyl, aryl, and C-1-linked saccharide. The compounds may also be used to treat other conditions, such as inflammatory bowel disease, autoimmune diseases, transplant rejection, septic shock, and for protection against irradiation damage. Novel celastrol derivatives are also disclosed.

Method and composition for treating hepatitis B

A method of treating inflammation in a subject by administering a therapeutically effective amount of a compound having the structure: ##STR1## where R.sub.1 to R.sub.4 are the same or different and are each selected from the group consisting of H, an alkylacyl group, an arylacyl group, or a C-1-linked saccharide.

Anti-inflammatory treatment method

This invention is directed to an adjuvant composition in the form of an emulsion which is comprised of an emulsion-forming amount of a non-toxic tetra-polyol or of a POP-POE block polymer and an immunopotentiating amount of a muramyldipeptide of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, where R and R.sub.1 are each independently H or acyl of 1 to 22 carbon atoms, R.sub.2 is optionally substituted alkyl or optionally substituted aryl, R.sub.3 is H, alkyl, or aryl, R.sub.4 is H or lower alkyl, X is L-alanyl, L-.alpha.-aminobutyryl, L-arginyl, L-asparginyl, L-aspartyl, L-cysteinyl, L-glutaminyl, L-glutamyl, glycyl, L-histidyl, L-hydroxyprolyl, L-isoleucyl, L-leucyl, L-lysyl, L-methionyl, L-ornithinyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tyrosyl, L-tryptophanyl, or L-valyl, and Y is D-glutamine, D-isoglutamine or D-isoasparagine. This invention is also directed to a vaccine containing an antigen and an adjuvant composition of the invention. This invention is also directed to a process of preparing an adjuvant composition and a vaccine of the invention. This invention is also directed to a kit for extemporaneous preparation of an adjuvant composition and a vaccine of the invention.

Vaccine adjuvant

Heterocyclic aminoalkyl esters of mycophenolic acid, and the derivatives and pharmaceutically acceptable salts thereof, are useful as immunosuppressive agents, anti-inflammatory agents, anti-tumor agents, anti-viral agents, and anti-psoriatic agents.

Treatment of autoimmune inflammatory, and psoriatic diseases with

The compounds and pharmaceutical compositions of Formula A, wherein Z is hydrogen or --C(O)R, Y is hydrogen or morpholinoethyl, and where R is lower alkyl or aryl, and the pharmaceutically acceptable salts thereof, are useful as immunosuppressive agents, particularly for treatment of allograft rejection, especially including cardiac allograft rejection, pancreatic allograft rejection and renal allograft rejection, and for treating autoimmune diabetes. ##STR1##

Treatment of autoimmune diseases with mycophenolic acid, and derivatives

A method of treating rheumatoid arthritis which method comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of the formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein: A is oxygen or sulfur;

Mycophenolic acid derivatives in the treatment of rheumatoid arthritis

The compounds and pharmaceutical compositions of Formula A, wherein Z is hydrogen or --C(O)R, where R is lower alkyl or aryl, and the pharmaceutically acceptable salts thereof, are useful as immunosuppressive agents, anti-inflammatory agents, anti-tumor agents, anti-viral agents, and anti-psoriatic agents. ##STR1##

Growing community of inventors

Belmont, CA, United States of America

Anthony C Allison