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OwnerCatherine A. Hession, Roy R. Lobb +4inventors
InventorsCatherine A. Hession, Roy R. Lobb, Susan E. Goelz, Laurelee Osborn, Christopher D. Benjamin, Margaret D. Rosa
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DNA sequences encoding endothelial cell-leukocyte adhesion molecules ELAMs, methods for producing such molecules, and ELAMs (including the specific molecules ELAM1 and VCAM1 and 1b) essentially free of normally associated animal proteins are disclosed. Antibodies against ELAMs are also disclosed. DNA sequences encoding molecules involved in leukocyte adhesion (MILAs), methods for producing such molecules and MILAs (including the specific molecule, CDX) essentially free of normally associated animal proteins are also disclosed. Antibody preparations which are reactive for MILAs and also disclosed. We disclose DNA sequences designated clone 7.2 and clone 1, which cause cells transformed with them to express 1,3-fucosyl transferases and which are involved in CDX expression. We also disclose protein 7.2 and protein 1 which are encoded by clone 7.2 and clone 1, respectively. We also disclose Pseudo-X and Pseudo-X2, proteins which cause COS cells and CHO cells to bind to ELAM1 and to be recognized by α-CDX antibodies. Methods for identifying molecules which inhibit binding of leukocytes to endothelial cells, methods for inhibiting leukocyte binding to endothelial cells, and methods for detecting acute inflammation are disclosed.
A DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof selected from the group consisting of:
A recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof, wherein said DNA sequence is selected from the group consisting of:
A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or fragment thereof, wherein said DNA sequence is selected from the group consisting of:
A cytokine-inducible expression control sequence derived from the nucleotide sequence of FIG. 7.
An ELAM or fragment thereof essentially free of normally associated animal proteins selected from the group consisting of ELAM1, the lectin-like domain of ELAM1, the EGF-like domain of ELAM1, the consensus cysteine repeat unit of ELAM1, soluble ELAM1, mature ELAM1, and ELAM1 fragments capable of binding to an ELAM1 ligand.
Hybridoma CDB.BBll.BC6 anti-ELAM1.
The monoclonal antibodies produced by hybridoma CDB.BB11.BC6 anti-ELAM1.
A DNA sequence encoding a MILA for ELAM1 or fragment thereof.
A recombinant DNA molecule comprising a DNA sequence encoding a MILA for ELAM1 or a fragment thereof.
A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding a MILA for ELAM1 or fragment thereof.
A MILA for ELAMI or a fragment thereof, substantially free of normally associated animal proteins.
Hybridoma SGB3B4.
The monoclonal antibodies produced by hybridoma SGB3B4.
An antibody preparation that is reactive to a MILA for ELAM1 but non-reactive to other proteins on the leukocyte cell surface.
A method for producing an antibody preparation reactive to a MILA for ELAM1 comprising the step of immunizing an organism with CDX or an antigenic fragment thereof.
A DNA sequence encoding an endothelial cell-leukocyte adhesion molecule or fragment thereof selected from the group consisting of
A recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof wherein said DNA sequence is selected from the group consisting of:
A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding an endothelial cell-leukocyte adhesion molecule (ELAM) or a fragment thereof, wherein said DNA sequence is selected from the group consisting of:
VCAM1 or VCAM1b or a fragment thereof essentially free of normally associated animal proteins.
A VCAM1 or VCAM1b polypeptide selected from the group consisting of domain 1 of VCAM1, domain 2 of VCAM1, domain 3 of VCAM1, domain 4 of VCAM1, domain 5 of VCAM1, domain 6 of VCAM1, domain 3 of VCAM1b, domain 3B of VCAM1b, domain 4 of VCAM1b, and combinations thereof.
An antibody preparation that is reactive for VCAM1 or VCAM1b but non-reactive for other adhesion molecules expressed on the endothelial cell surface.
A hybridoma producing monoclonal antibodies that recognize VCAM1.
A method for producing antibodies which recognize VCAM1 or VCAM1b, comprising the step of immunizing an organism with VCAM1 or VCAM1b or an antigenic fragment thereof.
A method for identifying molecules which inhibit binding of leukocytes to endothelial cells comprising the steps of:
A method for identifying molecules which inhibit binding of leukocytes to endothelial cells comprising the steps of:
A method of inhibiting adhesion between leukocytes and endothelial cells in a system containing them comprising the step of introducing an effective amount of an inhibitory agent into said system, wherein said inhibitory agent is selected from the group consisting of ELAMs or fragments thereof capable of binding to ELAM ligands, antibodies recognizing MILAs, ELAM ligands or fragments thereof capable binding to ELAMs, carbohydrates binding to ELAMS, and antibodies recognizing ELAMs.
A method of detecting inflammation comprising the step of administering a detectably labelled compound selected from the group consisting of ELAM ligands, ELAM-binding fragments of an ELAM ligand, and antibodies which recognize an ELAM.
A method of detecting inflammation comprising the steps of:
A recombinant DNA molecule coding on expression for an ELAM/immunoglobulin fusion protein comprising a DNA sequence coding on expression for an ELAM or fragment thereof and a DNA sequence coding on expression for the constant region of an immunoglobulin molecule.
An antisense nucleic acid against an ELAM or MILA mRNA comprising a nucleic acid sequence hybridizing to said mRNA.
A recombinant DNA molecule having a DNA sequence which, on transcription, produces an antisense ribonucleic acid against an ELAM or MILA mRNA, said antisense ribonucleic acid comprising a nucleic acid sequence hybridizing to said mRNA.
An ELAM-producing or MILA-producing cell line transfected with a recombinant DNA molecule having a DNA sequence which, on transcription, produces an antisense ribonucleic acid against an ELAM or MILA mRNA, said antisense ribonucleic acid comprising a nucleic acid sequence hybridizing to said mRNA.
A method for creating a cell line which exhibits reduced expression of an ELAM or MILA comprising transfecting an ELAM-producing or MILA-producing cell line with a recombinant DNA molecule having a DNA sequence which, upon transcription, produces an antisense ribonucleic acid against an ELAM or MILA mRNA, said antisense ribonucleic acid comprising a nucleic acid sequence hybridizing said mRNA.
A ribozyme which cleaves an ELAM or MILA mRNA.
A recombinant DNA molecule comprising a DNA sequence which, upon transcription, produces a ribozyme that cleaves an ELAM or MILA mRNA.
An ELAM-producing or MILA-producing cell line transfected with a recombinant DNA molecule comprising a DNA sequence which, upon transcription, produces a ribozyme that cleaves an ELAM or MILA mRNA.
A method for creating a cell line which exhibits reduced expression of an ELAM or MILA comprising transfecting an ELAM-producing or MILA-producing cell line with a recombinant DNA molecule that produces on transcription a ribozyme that cleaves an ELAM or MILA mRNA.
A method of treating inflammation comprising the step of administering an amount of a ribozyme that cleaves an ELAM mRNA or an ELAM ligand mRNA effective to reduce the production of ELAM or ELAM ligand.
An anti-idiotypic antibody preparation reactive to an ELAM or MILA.
A method for identifying an ELAM or ELAM-ligand which binds to any one of ELAM1, CDX, VCAM1, VCAM1b, or VLA4, comprising the steps of:
A method for identifying ELAM ligands which bind to any of the domains of VCAM1 or VCAM1b comprising the steps of:
A method for inhibiting VCAM1 or VCAM1b expression comprising the step of administering an effective dose of an antibody which recognizes IL-1, TNF, or IFN-γ.
A radioimmunoconjugate comprising an antibody conjugated to a nuclide, said antibody selected from the group consisting of antibodies recognizing VCAM1, antibodies recognizing VCAM1b, monoclonal antibody SGB3B4 and monoclonal antibody BB11.
An immunotoxin comprising an antibody recognizing VCAM1 or VCAM1b conjugated to a cell toxin.
A method for detecting VCAM1 or VCAM1b-producing cancer cells comprising the step of administering a radioimmunoconjugate having an antibody which recognizes VCAM1 or VCAM1b.
A method for treating cancer comprising the step of administering an effective dose of a radioimmunoconjugate or immunotoxin having an antibody which recognizes VCAM1 or VCAM1b.
A DNA sequence encoding a VCAM/ICAM fusion protein comprising DNA sequences for VCAM1 or VCAM1b domains binding a VCAM1 ligand and ICAM1 domains binding an ICAM1 ligand.
A VCAM/ICAM fusion protein comprising VCAM1 or VCAM1b domains binding a VCAM1 ligand and ICAM1 domains binding an ICAM1 ligand.
A method for treating tumors expressing ELAM1, VCAM1, VCAM1b or a ligand thereof comprising:
A method for enhancing the cytolytic properties of leukocytes against target cells expressing ELAMs or MILAs comprising transfecting said leukocytes with a recombinant expression vector including a gene coding for an ELAM or MILA molecule that binds to the ELAM or MILA expressed by said target cells, which recombinant expression vector is capable of expressing said gene in said leukocyte.
A method according to 137, wherein the target cell is a melanoma or a colon carcinoma.
A DNA sequence selected from the group consisting of:
A recombinant DNA molecule comprising a DNA sequence selected from the group consisting of:
A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence encoding an amino acid sequence of FIG. 9 or FIG. 10.
A process for producing a molecule that binds to ELAM1 comprising the step of expressing a DNA sequence encoding the amino acid sequence of FIG. 9 or FIG. 10 in a eukaryotic host cell.
A process for producing a cell that adheres to ELAM1 comprising the step of expressing a DNA sequence encoding the amino acid sequence of FIG. 9 or FIG. 10 in a eukaryotic host cell.
Pseudo-X or a fragment thereof capable of binding to α-CDX.
Pseudo-X2 or a fragment thereof capable of binding to α-CDX.
A molecule capable of binding to ELAM1 comprising the carbohydrate moiety of a protein or a fucose-containing portion thereof wherein the protein is selected from the group consisting of CDX, Pseudo-X or Pseudo-X2.
A method of inhibiting adhesion between leukocytes and endothelial cells in a system containing them comprising the step of introducing in said system an effective amount of a molecule capable of binding to ELAM1, which molecule comprises a carbohydrate moiety of a protein or a fucose-containing portion thereof, wherein the protein is selected from the group consisting of CDX, Pseudo-X and Pseudo-X2.
A small molecule that inhibits the activity of the 1,3-fucosyl transferases described herein.
A method of identifying small molecules that inhibit the activity of the 1,3-fucosyl transferases described herein comprising the steps of:
The use of a 1,3-fucosyl transferase in a process for synthesizing an organic compound.
A method of producing a 1,3 glycosidic bond between fucose and a fucose acceptor comprising the step of catalysis with a 1,3-fucosyl transferase as described herein.
Protein 7.2, protein 1, non-human homologues of protein 7.2 or protein 1 and biologically active fragments of any of the foregoing proteins.
A cytokine-inducible expression control sequence derived from the nucleotide sequence of FIG. 8.
Dependencies are inferred from the claim text.