Abstract: The present invention provides peptides with a specific affinity for glycosaminoglycan molecules. These peptides may have any number of functions, including but not limited to use as inhibitors of glycosaminoglycan-mediated processes, enhancers of glycosaminoglycan-mediated processes, and as molecular probes to identify the presence of a specific glycosaminoglycan. Peptides of the invention may be directed against any glycosaminoglycan, including hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, heparin, keratan sulfate, keratosulfate, chitin, chitosan 1, and chitosan 2. These isolated peptides may have therapeutic uses in the treatment or prevention of diseases involving infection, inflammatory diseases, cancer, infections, etc. The peptides may also have other biological functions such as contraception.
Type:
Grant
Filed:
March 22, 2000
Date of Patent:
November 25, 2003
Assignee:
The University of Texas System
Inventors:
Akira Takashima, Mark E. Mummert, Mansour Mohamadzadeh
Abstract: Compounds that selectively bind to expanded polyglutamine repeats are disclosed. Such compounds are characterized in that they bind to a first polyglutamine peptide consisting of 60 glutamine residues under conditions in which they do not bind to a second polyglutamine peptide consisting of 20 glutamine residues. Conjugates of such compounds, nucleic acids encoding the same, and methods of use thereof are also disclosed.
Type:
Grant
Filed:
February 9, 2001
Date of Patent:
October 14, 2003
Assignee:
Duke University
Inventors:
James R. Burke, Warren J. Strittmatter, Yoshitaka Nagai
Abstract: The present invention is directed to the identification of compounds in a compound library which can mediate the biological activity of a target receptor protein, even when the ligands which mediate that activity through binding to that receptor are not already known.
The method of the invention includes the following three steps:
(1) Screen a first combinatorial library for members binding to the target protein (TP) and hence capable of use as surrogates for the unknown ligand in steps (2) and (3).
(2) Screen a second library, for compounds which inhibit the binding of one or more surrogates from step (1) to TP, and, optionally.
(3) Determine whether the inhibitory compound mediates the biological activity of the said TP.
The first library is composed of peptides, peptoids and/or nucleic acids, and the second is not.
Type:
Grant
Filed:
April 30, 1998
Date of Patent:
September 9, 2003
Assignee:
Karo Bio AB
Inventors:
Dana M. Fowlkes, Brian K. Kay, Jeffrey A. Frelinger, Robin Parish Hyde-Deruyscher
Abstract: A pseudobioaffinity chromatography adsorbent adapted for use in selectively adsorbing immunoglobulins. In one embodiment, the adsorbent includes: (a) a solid support material; and (b) a ligand immobilized on the surface of the solid support material, said ligand being a compound of the formula
wherein Y1 is selected from the group consisting of S, SCH3+, O, NH, NCH3, CH2 and CR1R2 wherein at least one of R1 and R2 is not hydrogen; wherein each of Y2, Y3 and Y4 is selected from the group consisting of N, NCH3+, CH, and CR wherein R is not hydrogen; and wherein at least two of Y1, Y2, Y3 and Y4 are neither CH2, CH, CR nor CR1R2.
Abstract: The present invention provides peptides which can interact with VEGF and inhibit VEGF interaction with KDR or anti-VEGF antibody thereby inhibiting VEGF mediated angiogenesis or angiogeneis related diseases, polynucleotide encoding the peptides, vectors containing the polynucleotides, pharmaceutical compositions containing the peptides, and methods of inhibiting angiogenesis with the peptides.
Type:
Grant
Filed:
April 2, 2001
Date of Patent:
May 6, 2003
Assignee:
Institut Pasteur
Inventors:
Roselyne Tournaire, Caroline Demangel, Claude Derbin, Gerard Perret, Jean-Claude Mazie, Jean Plouet, Roger Vassy
Abstract: Peptoid compounds of Formula I and Formula II are disclosed
The compounds are useful in the treatment of matrix metalloproteinase-mediated disorders.
Type:
Grant
Filed:
July 23, 2001
Date of Patent:
March 11, 2003
Assignee:
Wisconsin Alumni Research Foundation
Inventors:
Donald T. Witiak, Paul J. Bertics, Yingsheng Zhang
Abstract: A method for preparing saccharide compositions which is reiterative and includes the following three steps.
(i) A glycosyltransferase capable of transferring a preselected saccharide unit to an acceptor moiety is isolated by contacting the acceptor moiety with a mixture suspected of containing the glycosyltransferase under conditions effective to bind the acceptor moiety and the glycosyltransferase and thereby isolate the glycosyltransferase. The acceptor moiety is a protein, a glycoprotein, a lipid, a glycolipid, or a carbohydrate.
(ii) The isolated glycosyltransferase is then used to catalyze the bond between the acceptor moiety and the preselected saccharide unit.
(iii) Steps (i) and (ii) are repeated a plurality of times with the intermediate product obtained in the first iteration of the method being used as the acceptor moiety of the second iteration.
Abstract: The present invention relates to permuted, chimeric nucleic acid libraries and methods of preparing such permuted, chimeric nucleic acid libraries.
Type:
Grant
Filed:
May 27, 1998
Date of Patent:
November 27, 2001
Assignee:
The Regents of the University of California
Inventors:
Robert A. Stull, Maria Pallavicini, Gary Green
Abstract: This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which include HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation.
Type:
Grant
Filed:
April 28, 1994
Date of Patent:
November 13, 2001
Assignees:
Whitehead Institute for Biomedical Research, Johns Hopkins Univ. School of Medicine, Biogen, Inc.
Inventors:
Alan Frankel, Carl Pabo, James G. Barsoum, Stephen E. Fawell, R. Blake Pepinsky
Abstract: A method is disclosed for producing a soluble conjugate vaccine, and preferably protein/polysaccharide conjugates. In this process, the polysaccharide is reacted with a reagent so as to provide a functional group on the polysaccharide molecule. Once the functional group is in place, the polysaccharide is reacted with a homobifunctional or heterobifunctional vinylsulfone to produce a vinylsulfone derivatized polysaccharide. Thereafter, the vinylsulfone derivatized polysaccharide is reacted with a protein to produce the conjugate. If desired, the protein may be derivatized with a functional group prior to the conjugation reaction step. In an alternative embodiment, the protein may be functionalized with a reactive group and then derivatized with the vinylsulfone group to produce a vinylsulfone derivatized protein. This protein may then be reacted with a polysaccharide to produce the conjugate. Optionally, the polysaccharide may be functionalized with a reactive group prior to the conjugation reaction.
Type:
Grant
Filed:
May 7, 1997
Date of Patent:
October 30, 2001
Assignee:
The Henry M. Jackson Foundation for the Advancement of
Military Medicine
Abstract: Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from three phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins of SH3 domains and glutathione S-transferase (GST). Preferred peptides are disclosed having a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.
Type:
Grant
Filed:
July 22, 1994
Date of Patent:
October 16, 2001
Assignee:
The University of North Carolina at Chapel Hill
Inventors:
Brian K. Kay, Andrew B. Sparks, Judith M. Thorn, Lawrence A. Quilliam, Channing J. Der
Abstract: Kalahide F, of formula I below, may be isolated from a sacoglossan. The compound may be used in the manufacture of pharmaceutical compositions or in the treatment of tumors or viral conditions.
Type:
Grant
Filed:
February 3, 1994
Date of Patent:
August 14, 2001
Assignee:
PharmaMar, S.A.
Inventors:
Paul J Scheuer, Mark T Hamann, Dolores G. Gravalos
Abstract: Unfucosylated huPAR polypeptides that contains huPA1-48 (SEQ ID NQ:22) are provided. These polypeptides are useful for treating diseases wherein antagonism of huPAR is therapeutically beneficial.
Type:
Grant
Filed:
December 23, 1998
Date of Patent:
July 31, 2001
Assignee:
Chiron Corporation
Inventors:
Steven Rosenberg, Jennifer R. Stratton-Thomas
Abstract: Cyclohexapeptidyl amine compounds are disclosed of the formula:
or its acid addition salt,
wherein:
R1 is H or OH;
R2 is H or OH;
R3 is QCnH2nNRVRVI, QCnH2nNRVRVIRVII+Y−, or Q(CH2)1-3CRVIIIRIXNHRX.
Type:
Grant
Filed:
April 30, 1993
Date of Patent:
July 31, 2001
Assignee:
Merck & Co., Inc.
Inventors:
James M. Balkovec, Frances Aileen Bouffard, James F. Dropinski, Robert A. Zambias
Abstract: It has been found that nonimmunosuppressive, cyclophilin-binding cyclosporins are useful in the treatment and prevention of AIDS and AIDS-related disorders. Such cyclosporins include novel Ciclosporin derivatives modified at the 4- and/or 5-positions.
Abstract: Peptide derivatives which are antagonists of neurokinin A. The derivatives have a modified peptide bond having a reduced amide and a fluorinated alkyl attached to the nitrogen atom of the modified peptide bond. For example, Asp-Ser-Phe-Val-Gly-Leu&PSgr;[CH2N(CH2CF3)]Leu(NH2).
Abstract: Endogenous and exogenous proteins, and fragments thereof, are chemically modified outside the body of an animal so that when injected into the animal they produce more antibodies against the unmodified protein than would injection of the unmodified protein or fragment alone. The chemical modification may be accomplished by attaching the proteins or fragments to carriers such as, for example, bacterial toxoids. The chemical modification can also be accomplished by polymerization of protein fragments. Proteins which can be modified include Follicle Stimulating Hormone and Human Chorionic Gonadotropin. The modified polypeptides may be administered to animals for the purpose of contraception, abortion or treatment of hormone-related disease states and disease disorders, treatment of hormone-associated carcinomas, and to boost the animals resistance to exogenous proteins, for example viral proteins.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
April 17, 2001
Assignee:
The Ohio State University Research Foundation
Abstract: The present invention deals with LHRH analogs which contain cytotoxic moieties, have influence on the release of gonadotropins from the pituitary in mammals (possess high agonistic or antagonistic activity) and have antineoplastic effect.
Type:
Grant
Filed:
January 25, 1993
Date of Patent:
April 10, 2001
Assignee:
The Administrators of the Tulane Educational Fund
Inventors:
Tamas Janaky, Attila Juhasz, Sandor Bajusz, Andrew V. Schally
Abstract: The present invention is directed to a novel depsipeptide has been isolated from a new marine strain L-13-ACM2-092 belonging to the family Micromonosporaceae. Its production by aerobic fermentation under controlled conditions of the strain, and the isolation and purification of PM-93135 are described herein. The compound and the fermentation broth demonstrate significant activity against several cancer cell lines. The compound also shows activity against several gram positive bacteria.
Type:
Grant
Filed:
September 24, 1997
Date of Patent:
April 10, 2001
Assignee:
Pharma Mar, s.a.
Inventors:
Julia Perez Baz, Francisco Romero Millan, Teresa Garcia De Quesada, Dolores Garcia Gravalos
Abstract: The invention relates to derivatives of hepatitis C virus amino acid sequences. These derivatives can be used to screen samples, such as blood, to determine if antibodies to hepatitis C virus are present.
Type:
Grant
Filed:
July 31, 1996
Date of Patent:
April 3, 2001
Assignee:
Roche Diagnostics GmbH
Inventors:
Christoph Seidel, Rupert Herrmann, Eva Hoess, Hans-Georg Batz