La Jolla Cancer Research Foundation

Boehringer Mannheim Gmbh

The Burnham Institute

Other

Burnham Institute for Medical Research

Kyowa Hakko Kogyo Co., Ltd.

La Jolla Cancer Research Center

La Jolla Cancer Research Foun.

Minoru Fukuda

Marti F Bierhuizen

Jun Nakayama

Rita Gerardy-Schahn

Matthias Eckhardt

Michiko N Fukuda

Satoshi Nakagawa

Katsutoshi Sasaki

Susumu Sekine

Tatsunari Nishi

Ritsuko Sawada

Kazumi Miura

Yoshio Hirabayashi

Akiko Kanamori

Edgar Ong

John B Lowe

Jiunn-chern Yeh

Shigeru Tsuboi

Masatomo Kawakubo

Tsutomu Katsuyama

Compositions useful for inhibiting the growth of bacteria, including bacteria that can cause gastric ulcers, are provided. In addition, transgenic organism that can produce such compositions are provided. Methods of using the compositions to treat or prevent gastric ulcers in a subject, including a human subject, also are provided.

Antimicrobial carbohydrates and methods of using same

In accordance with the present invention, there are provided peptides that bind to a member of the mammalian selectin family and inhibit the binding of a carbohydrate to the selectin. Invention peptides are useful to inhibit of the adhesion of cells containing particular cell-surface carbohydrates to cells containing cell-surface selectins. Also provided are pharmaceutical compositions comprising invention peptides useful in methods for inhibiting a carbohydrate from binding to a selectin, and in methods of inhibiting tumor cell metastasis in a subject.

Methods for inhibiting tumor metastasis, and peptides useful therefor

The present invention provides pharmaceutical preparations for anti-inflammation, anti-infection, inhibition of cancer metastasis etc., foods such as dairy products etc., and a method for improving proteins, as well as a method for diagnosis of inflammatory diseases and cancer malignancy. According to the present invention, there can be provided a polypeptide having poly-N-acetyllactosamine sugar chains synthesis-related activity, a process for producing the polypeptide, DNA coding for the polypeptide, a process for producing the DNA, a recombinant vector having the DNA integrated therein, a transformant carrying the recombinant vector, an antibody recognizing the polypeptide, a process for producing poly-N-acetyllactosamine sugar chains by use of the DNA or the polypeptide, diagnosis and treatment of diseases such as inflammations, cancers etc. by use of the DNA, the polypeptide or the antibody, determination and immunostaining of the polypeptide of the present invention by use of the antibody, a method for screening a compound varying the expression of a gene coding for the polypeptide, and a method for screening a substance varying the activity of the polypeptide.

Polypeptides

In accordance with the present invention, there are provided isolated mammalian Acetyl-Coenzyme A Transporter (AT) proteins, anti-AT antibodies, therapeutic compositions, and nucleic acids encoding such. Bioassays and therapeutic methods employing invention AT proteins are also provided.

Nucleic acid encoding a family of acetyl-coenzyme-a transporter proteins, and products related thereto

The present invention provides antagonists to cell adhesion useful in controlling the negative effects of inflammation, and the metastasis of cancer cells. These antagonists are ligands to E-selectin containing the sialyl Le structure, including sialyl Le glycoproteins, sialyl Le glycolipids, and sialyl Le oligsaccharides, and other related sialyl Le -containing molecules capable of inhibiting E-selectin mediated cell adhesion to endothelial cells. The present invention also provides antibodies against sialyl Le determinants capable of interrupting E-selectin mediated cell adhesion, which are also considered antagonists according to the present invention. The present invention also provides methods of using the antagonists of the present invention to reduce inflammation, and methods to inhibit the process of metastasis by carcinogenic cells. The present invention also provides nucleic acid molecules encoding the glycoprotein antagonists of the present invention, in particular soluble chimeric leukosialin, and vectors capable of expressing these nucleic acid molecules, as well as cells capable of producing sialyl Le positive recombinant glycoproteins. The present invention further provides a method of determining metastatic potential by comparing the efficiency of E-selectin-mediated adhesion of cell samples. In addition the present invention provides a method of producing a preferred antagonist of the present invention, sialyl Le positive glycoproteins, in particular, sialy Le positive chimeric leukosialin.

Leukosialin: Ig fusion proteins

In accordance with the present invention, there are provided peptides that bind to a member of the mammalian selectin family and inhibit the binding of a carbohydrate to the selectin. Invention peptides are useful to inhibit of the adhesion of cells containing particular cell-surface carbohydrates to cells containing cell-surface selecting. Also provided are pharmaceutical compositions comprising invention peptides useful in methods for inhibiting a carbohydrate from binding to a selectin, and in methods of inhibiting tumor cell metastasis in a subject.

Methods for inhibiting tumor metastasis, and peptides useful therfor

Sulfotransferases that synthesize the HNK-1 carbohydrate epitope by adding a sulfate group to GlcA&bgr;1&rarr;3Gal&bgr;1&rarr;4GlcNAc&bgr;1&rarr;R to form glycan sulfo&rarr;3GlcA&bgr;1&rarr;3Gal&bgr;1&rarr;4GlcNAc&bgr;1&rarr;R. They are exemplified by human (hu-HNK-1ST) and mouse (mHNK-1ST) sulfotransferases. Also provided are related peptides, antibodies, nucleic acids and methods.

Sulfotransferase for HNK-1 glycan

The present invention provides a substantially pure C2GnT-M polypeptide or a functional fragment or derivative thereof, wherein C2GnT-M is characterized as a polypeptide having core 2, core 4 and I branching .beta.-1.fwdarw.6-N-acetylglucosaminyltransferase activities. The invention also provides a substantially pure C2GnT-M peptide, wherein the peptide is immunogenic. Also provided is a method of modifying an acceptor molecule by contacting the acceptor molecule with a substantially pure C2GnT-M polypeptide or a functional fragment under conditions that allow addition of core 2, core 4 or I GlcNAc linkages to the acceptor molecule, and an acceptor molecule produced by the method. Also provided is a substantially pure nucleic acid molecule having substantially the nucleic acid sequence designated SEQ ID NO: 1, or the complement thereof. The invention also provides a substantially pure nucleic acid molecule encoding C2GnT-M or a functional fragment or derivative thereof, or the complement of the nucleic acid molecule, wherein C2GnT-M is characterized as a polypeptide having core 2, core 4 and I branching P-1.fwdarw.6-N-acetylglucosaminyltransferase activities. Also provided are vectors and host cells containing nucleic acid molecules encoding C2GnT-M or a functional fragment or derivative thereof. A substantially pure oligonucleotide having a nucleotide sequence corresponding to or complementary to at least 15 nucleotides from SEQ ID NO: 1, SEQ ID NO: 9 or SEQ ID NO: 13 is also provided. The invention further provides an antibody or antigen binding fragment thereof that is specifically reactive with C2GnT-M or with a functional fragment or derivative hereof. Methods of detecting the presence of C2GnT-M in sample are also provided.

.beta.-1-6-N-acetylglucosaminyltransferase that forms core 2, core 4 and

A protein having polysialyl transferase activity, which a) is a product of a prokaryotic or eukaryotic expression of an exogenous DNA, b) is coded by the DNA sequence shown in SEQ ID No. 1, c) is coded by the DNA sequences which hybridize with the sequences SEQ ID No. 1 and/or SEQ ID No. 3, d) is coded by DNA sequences which if there was no degeneracy of the genetic code, would hybridize with the sequences defined in b) to c), and e) catalyzes the polycondensation of .alpha.-2,8-linked sialic acids, and its related nucleic acid molecules and fragments are useful for the production of therapeutic agents for tumor therapy.

Isolated nucleic acid molecules which encode mammalian or rodent 2,8

Isolated nucleic acid molecules encoding polysialyl transferases, and the polysialyl transferases themselves are disclosed. SEQ ID NOS: 1, 2, 7 and 8 present examples of these. The nucleic acid molecules and the proteins can be used diagnostically or therapeutically. Additionally, antisense oligonucleotides and antibodies are described, which can also be used diagnostically or therapeutically.

Isolated polysialyl transferases

Nucleic acid encoding a family of acetyl-coenzyme-A transporter

Isolated nucleic acid molecules which hybridize to polysialyl

The present invention provides an isolated nucleic acid molecule encoding both a soluble and membrane-bound human .beta.-1,6-N-acetylglucosaminyltransferase, the I-branching enzyme (IGnT). The invention also provides vectors containing the isolated nucleic acid molecule encoding human IGnT as well as recombinant host cells transformed with the vectors. The invention further provides a method of preparing a membrane-bound form of human IGnT and methods of preparing and purifying soluble human IGnT and active fragments of either form. Also provided are antisense oligonucleotides complementary to a nucleic acid molecule encoding a human IGnT or an active fragment thereof, antibodies directed to the human IGnT, pharmaceutical compositions related to the human IGnT and transgenic nonhuman mammals expressing DNA encoding normal or mutant human IGnT. Also provided are methods for regulating the expression of human IGnT and methods for modifying a biological function mediated by the regulatory activity of human IGnT. Methods of detecting the presence of linear polylactosaminoglycans expressing i antigenic determinants on a cell surface also are provided.

Growing community of inventors

San Diego, CA, United States of America

Minoru Fukuda