Abstract: Disclosed is the characterization and purification of DNA encoding numerous polypeptides factors useful for the inhibition of cell (particularly, Schwann cell) proliferation. These factors are useful for the treatment of neural tumors. Also disclosed are the DNA sequences encoding novel polypeptides which may have use as agents which inhibit cell proliferation. Methods for the synthesis, purification, and testing of both known and novel polypeptides for their use as therapeutic and diagnostic aids in the treatment of diseases are also provided. Methods are also provided for the use of these polypeptides for the preparation of antibody probes. Such probes have diagnostic and therapeutic use in diseases involving neural and glial cells.
Abstract: Platelet-specific, chimeric immunoglobulin and immunoglobulin fragments are described. The chimeric molecules are made up of a nonhuman antigen binding region and a human constant region. Preferred immunoglobulins are specific for glycoprotein IIb/IIIa receptor in its complexed form; they block ligand binding to the receptor and prevent platelet aggregation. The immunoglobulins are useful in anti-thrombotic therapy when administered alone or in conjunction with thrombolytic agents, as well as in thrombus imaging.
Type:
Grant
Filed:
May 17, 1995
Date of Patent:
March 2, 1999
Assignees:
Centocor, Inc., The Research Foundation of State of New York
Abstract: The invention provides an antibody specific for carcinoembryonic antigen (CEA) which has a dissociation constant (Kd; of less than 5.0 nM for said antigen. The antibody is generally a single chain Fv (scFv) antibody. The antibody was initially obtained by screening a bacteriophage library for phage expressing high affinity CEA antibody. The antibody is useful for diagnosis and therapeutic treatment of colorectal tumors.
Type:
Grant
Filed:
July 2, 1996
Date of Patent:
March 2, 1999
Assignee:
Cancer Research Campaign Technology Limited
Inventors:
Kerry Anne Chester, Robert Edward Hawkins, Richard Henry John Begent
Abstract: Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
March 2, 1999
Assignees:
The Scripps Research Institute, Board of Regents, The University of Texas System
Abstract: The invention provides a human nucleotide pyrophosphohydrolase (NTPPH-1) and polynucleotides which identify and encode NTPPH-1. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention also provides methods for treating disorders associated with expression of NTPPH-1.
Type:
Grant
Filed:
August 27, 1997
Date of Patent:
March 2, 1999
Inventors:
Peter Mitchell, Nancy Hutchinson, Michael Lawton, Holly Magna, Sue Yocum, Lynn E. Murry
Abstract: The present invention pertains to a system and method for predicting the protein fold of a target amino acid residue sequence of unknown protein structure. A target sequence is represented by a sequence of residue variability types that utilizes positional variability information present in an associated family of homologous sequences to the target sequence. The use of the positional variability information increases the likelihood of matching the target sequence with a known protein structure. In a first preferred embodiment, a target sequence is mapped into a sequence of residue variability types that are based on the solubility variability present between amino acid residues in homologous sequences. In a second preferred embodiment, each residue variability type represents a cluster of residue types at each position of aligned sets of homologous protein sequences. Each distinct cluster represents a pattern of residue variability at various positions in sets of homologous protein sequences.
Abstract: Methods and compositions for determining the tumor suppressor status of cells are described, preferably as pertaining to the p53 status of tumor cells, and preferably in vivo using a recombinant construct consisting of a first polynucleotide sequence that encodes a reporter molecule and a second p53 binding polynucleotide sequence that is operably linked to the first polynucleotide sequence such that binding of p53 to the second polynucleotide sequence causes the expression of the reporter molecule which can be detected or quantified.
Abstract: Disclosed is DNA encoding a single-chain Fv (sFv) polypeptide defining a binding site which exhibits the immunological binding properties of an immunoglobulin molecule which binds c-erbB-2 or a c-erbB-2-related tumor antigen, the sFv includes at least two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each of the polypeptide domains includes a set of complementarity determining regions (CDRs) interposed between a set of framework regions (FRs), the CDRs conferring immunological binding to the c-erbB-2 or c-erbB-2-related tumor antigen.
Type:
Grant
Filed:
December 12, 1994
Date of Patent:
March 2, 1999
Assignees:
Chiron Corporation, Creative BioMoelcules, Inc.
Inventors:
James S. Huston, L. L. Houston, David B. Ring, Hermann Oppermann
Abstract: Antibodies that bind a protein gp39 (also referred to as CD40 ligand) are disclosed. Preferably, the antibodies are monoclonal antibodies of an IgG1 isotype and bind human gp39. In a preferred embodiment, an antibody of the invention binds an epitope recognized by a monoclonal antibody 24-31, produced by a hybridoma 24-31 (ATTC Accession No. HB11712) or binds an epitope recognized by a monoclonal antibody 89-76, produced by a hybridoma 89-76 (ATCC Accession No. HB 11713). Pharmaceutical compositions comprising the antibodies of the invention are also disclosed. The antibodies of the invention are useful for inhibiting B cell proliferation and differentiation, T cell responses and for inducing T cell tolerance. Nucleic acid molecules encoding anti-gp39 antibodies, or portions thereof, as well as expression vectors and host cells incorporating said nucleic acid molecules, are also encompassed by the invention.
Type:
Grant
Filed:
March 27, 1998
Date of Patent:
March 2, 1999
Assignees:
Trustees of Dartmouth College, Bristol-Myers Squibb Company
Inventors:
Randolph J. Noelle, Teresa M. Foy, Alejandro Aruffo, Jeffrey A. Ledbetter
Abstract: The invention provides for the production of several humanized murine antibodies specific for the antigen Lewis Y, which is recognized by the murine antibody Lewis Y. The Lewis Y antigen is expressed in normal tissues but the level of expression is higher in certain tumor types so that the antigen can be used as a marker for cells of some breast, colon, gastric, esophageal, pancreatic, duodenal, lung, bladder and renal carcinomas and gastric and islet cell neuroendocrine tumors. The invention also provides for numerous polynucleotide encoding humanized Lewis Y specific antibodies, expression vectors for producing humanized Lewis Y specific antibodies, and host cells for the recombinant production of the humanized antibodies. The invention also provides methods for detecting cancerous cells (in vitro and in vivo) using humanized Lewis Y specific antibodies. Additionally, the invention provides methods of treating cancer using humanized Lewis Y specific antibodies.
Type:
Grant
Filed:
May 20, 1997
Date of Patent:
February 23, 1999
Assignee:
Memorial Sloan Kettering Cancer Center
Inventors:
Kathryn Lesley Armour, Francis Joseph Carr, Lloyd J. Old, Elisabeth Stockert, Sydney Welt, Kunio Kitamura, Pilar Garin-Chesa
Abstract: OLRCC15 receptor polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing OLRCC15 receptor polypeptides and polynucleotides in the design of protocols for the treatment of infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; pain; cancers; anorexia; bulimia; asthma; Parkinson's disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; asthma; allergies; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others and diagnostic assays for such conditions.
Abstract: The present invention provides polynucleotides which identify and encode a novel human nm23-like protein (H-nm23). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding H-nm23 and for a method for producing the protein. The invention also provides for the use of substantially purified H-nm23 for the treatment of diseases associated with the expression of H-nm23. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotides which hybridize with naturally occurring sequences encoding H-nm23 and antibodies which specifically bind to the protein.
Abstract: Immunoconjugates effective for treating cancers and autoimmune diseases in humans are provided which comprise a tyrosine kinase inhibitor linked to a ligand targeting a cell surface receptor which are specifically capable of inhibiting receptor associated tyrosine kinases.
Abstract: Methods for assigning a quantitative score to the relatedness of aligned polymorphic biopolymer sequences such that small differences between otherwise identical sequences are highlighted are disclosed, including computer systems and program storage devices for carrying out the methods on a computer. Specifically, the methods of the invention comprise the steps of providing a test sequence and a basis set of sequences such that the test sequence and the basis set of sequences are aligned; determining the identity of a monomer unit at a position m in the test sequence; assigning a value of 1 to a local matching probability x.sub.m if the monomer unit at position m in the test sequence matches any members of the basis set at position m, or, assigning a value of between 0 and 1 to a local matching probability x.sub.m if the monomer unit at position m in the test sequence does not match any members of the basis set at position m.
Abstract: A method for the treatment of asthma is disclosed. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4, a protein expressed on the surface of certain leukocytes such as eosinophils.
Abstract: Monoclonal antibodies to adenocarcinoma cells, and, in particular, breast carcinoma cells, are produced by a hybridoma formed by fusing mouse lymphocytes and mouse myeloma cells. The monoclonal antibodies are capable of shrinking solid tumors associated with human breast. The monoclonal antibodies identify an antigen associated with carcinomas of ductal lineage. The monoclonal antibodies, specifically, F36/22 monoclonal antibodies, can be used diagnostically and therapeutically.
Abstract: Anti-CD4 antibody homologs, DNA sequences and recombinant DNA molecules encoding them, prophylactic, immunotherapeutic and diagnostic compositions comprising those antibody homologs, and methods for preventing or treating diseases in mammals, including humans, caused by infective agents whose primary targets are CD4.sup.+ lymphocytes. Such diseases include acquired immune deficiency syndrome ("AIDS"), AIDS related complex, and human immunodeficiency virus infection.
Type:
Grant
Filed:
November 27, 1991
Date of Patent:
February 16, 1999
Assignee:
Biogen, Inc.
Inventors:
Linda C. Burkly, Patricia L. Chisholm, David W. Thomas, Margaret D. Rosa, Joseph J. Rosa
Abstract: Conjugates of a carrier molecule and an organic molecule producing singlet oxygen after irradiation are useful in diagnostic and therapeutic applications. The organic molecule is a terthienyl or terfuranyl compound derivatized to react with amino, thiol, or saccharide groups of the carrier molecule. Suitable carrier molecules include antibodies, peptides, haptamers, sugars, and other analogous molecules which direct the organic molecule to a biological target.
Type:
Grant
Filed:
November 22, 1996
Date of Patent:
February 9, 1999
Assignees:
Giovanni Neri, L. Molenti & C. Dei Fratelli Alitti Societa' Di Esercizio Societa' Per Azioni
Abstract: The present invention provides cytotoxic Epstein-Barr virus T-cell epitopes. The epitopes are selected from the group consisting of QAKWRLQTL, RYSIFFDY, HLAAQGMAY, YPLHEQHGM, SVRDRLARL, AVLLHEESM, VSFIEFVGW, FRKAQIQGL, PYLFWLAAI, TVFYNIPPMPL, PGDQLPGFSDGRACPV, VEITPYKPTW, and variants thereof. In addition, the present invention provides compositions including these epitopes for use in inducing CTL's in a subject.
Type:
Grant
Filed:
January 27, 1997
Date of Patent:
February 9, 1999
Assignee:
The Council of the Queensland Institute of Medical Research
Inventors:
Denis James Moss, Scott Renton Burrows, Rajiv Khanna, Beverley Mavis Kerr, Jacqueline Margaret Burrows, Andreas Suhrbier
Abstract: The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab').sub.2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab').sub.2 -LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
February 9, 1999
Assignee:
Bristol-Myers Squibb Company
Inventors:
Ingegerg Hellstrom, Karl Erik Hellstrom, Kim Folger Bruce, George J. Schreiber