Abstract: Tumor cells modified to express a T cell costimulatory molecule are disclosed. In one embodiment, the costimulatory molecule is a CD28/CTLA4 ligand, preferably a B lymphocyte antigen B7. The tumor cells of the invention can be modified by transfection with nucleic acid encoding a T cell costimulatory molecule, by using an agent which induces or increases expression of a T cell costimulatory molecule on the tumor cell surface or by coupling a T cell costimulatory molecule to the tumor cell surface. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor. A method for specifically inducing a CD4.sup.
Type:
Grant
Filed:
September 23, 1998
Date of Patent:
November 21, 2000
Assignees:
Genetics Institute, Inc., Dana-Farber Cancer Institute, Presidents and Fellows of Harvard College
Inventors:
Suzanne Ostrand-Rosenberg, Sivasubramanian Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
Abstract: Purified BMP-2 and BMP-4 proteins and processes for producing them are disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.
Type:
Grant
Filed:
June 14, 1991
Date of Patent:
November 21, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Elizabeth A. Wang, John M. Wozney, Vicki A. Rosen
Abstract: Provided is a fusion molecule comprising a DNA sequence encoding a thioredoxin-like protein fused to a DNA sequence encoding a second peptide or protein. The peptide or protein may be fused to the amino terminus of the thioredoxin-like molecule, the carboxyl terminus of the thioredoxin-like molecule, or within the thioredoxin-like molecule, for example at the active-site loop of the molecule. The fusion molecule may be modified to introduce one or more metal-binding/chelating amino-acid residues to aid in purification. Expression of this fusion molecule under the control of a regulatory sequence capable of directing its expression in a desired host cell, produces high levels of stable and soluble fusion protein. The fusion protein, located in the bacterial cytoplasm, may be selectively released from the cell by osmotic shock or freeze/thaw procedures. It may be optionally cleaved to liberate the soluble, correctly folded heterologous protein from the thioredoxin-like portion.
Type:
Grant
Filed:
March 4, 1997
Date of Patent:
November 7, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
John McCoy, Elizabeth DiBlasio-Smith, Kathleen Grant, Edward R. LaVallie
Abstract: Disclosed are methods, DNA sequences, vectors and cell lines useful for the rapid generation of stable mammalian cell lines expressing high levels of recombinant proteins.
Type:
Grant
Filed:
October 20, 1998
Date of Patent:
October 24, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Kathleen Tomkinson, Monique Davies, John McCoy
Abstract: The invention provides a novel calcium-independent cytosolic phospholipase A.sub.2 -Gamma enzyme, polynucleotides encoding such enzyme and methods for screening unknown compounds for anti-inflammatory activity mediated by the arachidonic acid cascade.
Type:
Grant
Filed:
July 9, 1997
Date of Patent:
September 19, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Chuanzheng Song, Ronald Kriz, John Knopf
Abstract: This invention provides a chimeric DNA molecule comprising a sequence encoding a chemokine polypeptide covalently attached to a heterologous polypeptide, the encoded chimeric polypeptide, and uses thereof.
Type:
Grant
Filed:
February 28, 1997
Date of Patent:
August 8, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Stephen H. Herrmann, Stephen L. Swanberg
Abstract: Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
July 4, 2000
Assignees:
Dana-Farber Cancer Institute, Genetics Institute, Inc.
Inventors:
Gordon J. Freeman, Lee M. Nadler, Gary S. Gray
Abstract: Polynucleotides encoding human CTLA-8 related proteins are disclosed. Human CTLA-8 proteins and methods for their production are also disclosed. Methods of treatment using human CTLA-8 proteins, rat CTLA-8 proteins and herpesvirus herpes CTLA-8 proteins are also provided.
Type:
Grant
Filed:
July 18, 1996
Date of Patent:
June 13, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Kenneth Jacobs, Kerry Kelleher, McKeough Carlin, Samuel Goldman, Debra Pittman, Sha Mi, Steven Neben, Joanne Giannotti, Margaret M. Golden-Fleet
Abstract: A novel mammalian cytokine, IL-11, and processes for producing it are disclosed. IL-11 may be used in pharmaceutical preparations for stimulating and/or enhancing cells involved in the immune response and cells involved in the proper functioning of the hematopoietic system.
Type:
Grant
Filed:
July 24, 1998
Date of Patent:
May 23, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Yu-Chung Yang, Frances K. Bennett, Stephan R. Paul
Abstract: Polynucleotides encoding the MU-1 hematopoietin receptor superfamily chain and fragments thereof are disclosed. MU-1 proteins and methods for their production are also disclosed.
Abstract: Polynucleotides encoding human CTLA-8 and related proteins are disclosed. Human CTLA-8 proteins and methods for their production are also disclosed. Methods of treatment using human CTLA-8 proteins, rat CTLA-8 proteins and herpesvirus herpes CTLA-8 proteins are also provided.
Type:
Grant
Filed:
March 4, 1998
Date of Patent:
March 28, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Kenneth Jacobs, Kerry Kelleher, McKeough Carlin, Samuel Goldman, Debra Pittman, Sha Mi, Steven Neben, Joanne Giannotti, Margaret M. Golden-Fleet
Abstract: Purified Bone Morphogenetic Protein (BMP)-9 proteins and processes for producing them are disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair, and in hepatic growth and function.
Type:
Grant
Filed:
December 4, 1996
Date of Patent:
March 7, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Vicki A. Rosen, John M. Wozney, Anthony J. Celeste, Scott R. Thies, Jeffrey R. Song
Abstract: Purified Bone Morphogenetic Protein (BMP)-9 proteins and processes for producing them are disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair, and in hepatic growth and function.
Abstract: Purified BMP-15-related proteins and processes for producing them are disclosed. DNA molecules encoding the BMP-15-related proteins are also disclosed. The proteins may be used in the treatment of bone and cartilage and/or other connective tissue defects and in wound healing and related tissue repair.
Type:
Grant
Filed:
December 2, 1997
Date of Patent:
March 7, 2000
Assignees:
Genetics Institute, Inc., Vanderbilt University
Inventors:
Anthony J. Celeste, Jennifer L. Dube, Karen M. Lyons, Brigid Hogan
Abstract: Purified BMP-17 and BMP-18 proteins and processes for producing them are disclosed. DNA molecules encoding the BMP-17 and BMP-18 proteins are also disclosed. The proteins may be used in the treatment of bone, cartilage, other connective tissue defects and disorders, including tendon, ligament and meniscus, in wound healing and related tissue repair, as well as for treatment of disorders and defects to tissues which include epidermis, nerve, muscle, including cardiac muscle, and other tissues and wounds, and organs such as liver, lung, epithelium, brain, spleen, cardiac, pancreas and kidney tissue. The proteins may also be useful for the induction of growth and/or differentiation of undifferentiated embryonic and stem cells.
Abstract: The present invention relates to a novel family of purified proteins, and compositions containing such proteins, which compositions are useful for the induction of tendon/ligament-like tissue formation, wound healing and ligament and other tissue repair. The present invention further relates to DNA molecules, vectors and host cells useful for production of such proteins.
Type:
Grant
Filed:
November 2, 1994
Date of Patent:
February 22, 2000
Assignee:
Genetics Institute, Inc.
Inventors:
Anthony J. Celeste, John M. Wozney, Vicki A. Rosen, Neil M. Wolfman, Gerald H. Thomsen, Douglas A. Melton
Abstract: The present invention relates to a process for purifying recombinant coagulation factor VIII by loading an aqueous solution containing factor VIII onto a hydrophobic interaction chromatography (HIC) gel, wherein at least one surfactant is present in the aqueous solution and/or a buffer solution used to equilibrate the gel prior to loading the aqueous solution onto the gel. The presence of a surfactant when loading the solution containing factor VIII onto the HIC gel, makes it possible to efficiently separate the intact and active factor VIII molecules from molecules with structural deviations. With the present invention it is further possible to reduce the content of DNA and/or CHO cell contaminants considerably and increase the activity of the factor VIII product to a hitherto unknown extent.
Abstract: Disclosed herein is a method of determining whether a first protein is capable of physically interacting with a second protein, involving: (a) providing a host cell which contains (i) a reporter gene operably linked to a protein binding site; (ii) a first fusion gene which expresses a first fusion protein, the first fusion protein including the first protein covalently bonded to a binding moiety which is capable of specifically binding to the protein binding site; and (iii) a second fusion gene which expresses a second fusion protein, the second fusion protein including the second protein covalently bonded to a gene activating moiety and being conformationally-constrained; and (b) measuring expression of the reporter gene as a measure of an interaction between the first and the second proteins. Also disclosed are methods for assaying protein interactions, and identifying antagonists and agonists of protein interactions. Proteins isolated by these methods are also discussed.
Type:
Grant
Filed:
July 20, 1995
Date of Patent:
December 21, 1999
Assignees:
The General Hospital Corporation, Genetics Institute, Inc.
Inventors:
Roger Brent, John M. McCoy, Timm H. Jessen
Abstract: Methods are provided for the modulation of the effects of GDF-8 and BMP-11, particularly on neural and muscular disorders administration of follistatin for treating neural, muscle, disorders which are characterized by an abnormality in the levels or activity of GDF-8 or BMP-11.