The Dow Chemical Company

Dendritech Inc.

University of Michigan

Roberta C Cheng

William Jack Kruper, Jr

Donald A Tomalia

Ian A Tomlinson

Michael J Fazio

Larry R Wilson

David M Hedstrand

Donald A Kaplan

David A Wilson

Jaime Simon

Joseph R Garlich

William A Fordyce

Kenneth McMillan

Garry E Kiefer

Norman G Moll

Rui Yin

Karen M McCoy

Herbert M Brothers, Ii

Richard Keith Frank

Robert A Houtchens

Ritchie A Wessling

Donald L Schmidt

James R Baker, Jr

R Keith Frank

William J Kruper

Linneaus C Dorman

Yong Hsu

David Scott Edwards

John W Bozzelli

Anna U Bielinska

Chu W Jung

Douglas R Swanson

Bartley Dean Maxon

William F Goeckeler

Jolanta F Kukowska-Latallo

Carol C Epstein

Ralph Spindler

William F Goeckleler

Sharon Braughman

Sharon Baughman

William F Goeckler

Jennifer A Johnson

Scott L Klakamp

Donald A Kaplan, Deceased

Lars T Piehler

June W Klimash

Starburst conjugates which are composed of at least one dendrimer in association with at least one unit of a carried agricultural, pharmaceutical, or other material have been prepared. These conjugates have particularly advantageous properties due to the unique characteristics of the dendrimer.

Dense star polymer conjugates as dyes

Starburst conjugates

Dendritic polymers containing disulfide functional groups which are essentially inert under non-reducing conditions, but which form sulfhydryl groups upon being subjected to a reducing agent are prepared by synthesizing dendritic polymers having a core with a disulfide linkage or by reacting a dendritic polymer with a molecule containing a disulfide linkage and reactive terminal groups. In one aspect of the invention, dendritic polymers having a single disulfide functional group at the core are provided. The single disulfide group at the core can be reduced to form two sulfhydryl groups to which other molecules, such as proteins, oligonucleotides, peptides, hormones, other dendritic polymers, non-dendritic polymers, etc., can be bound. Applications for the disulfide functionalized dendritic polymers include formation of differentiated dendrimers, formation of binding reagents for diagnostics, drug delivery, gene therapy and magnetic resins imaging, and in the preparation of self-assembled dendrimer monolayers on a quartz crystal resonators to provide dendrimer-modified electrodes which are useful for detecting various ions or molecules. In another aspect of the invention, dendritic polymers having sulfhydryl terminals are provided. The sulfhydryl terminated dendritic polymers can be used to prepare stable, curable resins composition which can undergo cross linking when subjected to a reducing agent.

Disulfide-containing dendritic polymers

A group conjugates having a functionalized polyaminocarboxylate chelant that form complexes with rare earth-type metal ions, covalently attached to an antibody or antibody fragment, can be used for therapeutic and/or diagnostic purposes.

Macrocyclic tetraazacyclododecane conjugates and their use as diagnostic

Dendritic polymer conjugates which are composed of at least one dendrimer in association with at least one unit of a carried material, where the carrier material can be a biological response modifier, have been prepared. The conjugate can also have a target director present, and when it is present then the carried material may be a bioactive agent. Preferred dendritic polymers are dense star polymers, which have been complexed with biological response modifiers. These conjugates and complexes have particularly advantageous properties due to their unique characteristics.

Bioactive and/or targeted dendrimer conjugates

A group of functionalized polyaminocarboxylate chelants that form complexes with rare earth-type metal ions are disclosed. The complexes, covalently attached to an antibody or antibody fragment, can be used for therapeutic and/or diagnostic purposes.

Macrocyclic ligands and complexes

Dense star polymer conjugates which are composed of at least one dendrimer in association with at least one unit of a carried agricultural, pharmaceutical, or other material have been prepared. These conjugates have particularly advantageous properties due to the unique characteristics of the dendrimer.

Dense star polymer conjugates

A group of functionalized macrocyclic polyaminocarboxylate chelants that form complexes with rare earth-type metal ions are disclosed. The complexes, covalently attached to an antibody or antibody fragment, can be used for therapeutic and/or diagnostic purposes for cancer.

Macrocyclic congugates and their use as diagnostic and therapeutic agents

The subject invention concerns a process for stabilizing intact or ruptured microbial cells having glucose isomerase associated therewith. Specifically exemplified is a process for stabilizing glucose isomerase producing cells of a microorganism belonging to the genus Ampullariella. In the invention process the whole or ruptured microbial cells are contacted with a partially carboxyalkylated- or partially phosphonoalkylated-cationic polyelectrolyte, for example, a partially carboxymethylated polyethyleneimine to flocculate and stabilize the cells. The flocculated cells are further stabilized by encapsulation with a partially carboxyalkylated- or partially phosphonoalkylated-cationic polyelectrolyte. The encapsulation can be done prior to or after the flocculated cells are crosslinked. The net effect is manifested by a dramatic increase in the half-life of the glucose isomerase.

Stabilization of intracellular enzymes

Polysulfonium salts that can react with nucleophilic groups and covalently cross-link are used to immobilize enzymes or enzyme-containing cellular material. Some of the polysulfonium salts can both flocculate and covalently cross-link. Replacement of the cross-linker, glutaraldehyde, with the polysulfonium salt results in greater retention of enzyme activity during immobilization. Immobilization is carried out by forming a mixture of an enzyme or enzyme-containing cellular material and the polysulfonium salt and subjecting the mixture to conditions such that sulfonium ions react with nucleophilic groups contained by the enzyme or cellular material to form a covalently cross-linked and water insoluble product. The enzyme or cellular material may be flocculated with a flocculating agent prior to cross-linking with the polysulfonium salt. The polysulfonium salt can be a polymer containing sulfonium groups.

Enzyme immobilization with polysulfonium salts

Extracellular enzymes are stabilized with a carboxyalkylated or phosphonoalkylated polymer having a molecular weight of at least 500 Daltons. Exemplified is the stabilization of the enzyme glucose isomerase used in a process to convert D-glucose to D-fructose. In a preferred embodiment of the invention the feedstream containing the substrate is contacted initially with the stabilizer and then with the enzyme. In this system the stabilizer and enzyme are maintained in separate reactors. This separation, advantageously, results in a higher half-life for the enzyme.

Stabilization of glucose isomerase

A process is disclosed for the chemical immobilization of biological material such as bacteria and enzymes containing an active hydrogen with a vinyl addition polymer of an isocyanatoalkyl ester of an ethylenically unsaturated carboxylic acid. The vinyl addition polymer is versatile in that it can be copolymerized with varying amounts and types of comonomers.

Immobilization of biological matter via copolymers of isocyanatoalkyl

Fibrinogen peptide derivatives which have biological activity as anticoagulants of blood having the dipeptide moiety prolylarginine or the tripeptide moiety glycylprolylarginine, e.g., L-prolyl-L-arginine benzyl ester p-toluenesulfonate trifluoroacetate, glycyl-L-prolyl-L-arginine benzyl ester p-toluenesulfonate trifluoroacetate, N-t-butyloxycarbonyl-L-prolyl-L-arginine benzyl ester p-toluenesulfonate methanolate, N-benzyloxycarbonyl-prolyl-L-arginine benzyl ester p-toluenesulfonate methanolate and N-t-butyloxycarbonylglycol-L-prolyl-L-arginine benzyl ester p-toluenesulfonate.

Fibrinogen peptide derivatives

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Midland, MI, United States of America

Roberta C Cheng