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:
November 3, 1993
Date of Patent:
January 12, 1999
Assignees:
Repligen Corporation, Dana-Farber Cancer Institute, President and Fellows of Harvard College
Inventors:
Suzanne Ostrand-Rosenberg, Sivasubramanian Baskar, Laurie H. Glimcher, Gordon J. Freeman, Lee M. Nadler
Abstract: Disclosed are (1) methods for identifying natural and synthetic sequences having binding specificity for glycan-binding proteins, including proteins that act as effectors of biological activity, (2) compositions and methods of producing protein-specific glycosaminoglycan sequence and ligand antagonists capable of modulating the effector function of these ligands, and therapeutic compositions comprising these antagonists; and 3) compositions and methods for producing protein-specific glycosaminoglycan sequence analogs useful as agonists, and therapeutic compositions comprising these agonists.
Abstract: The invention relates to novel chemokine-like proteins that include two or more newly discovered active domains from different chemokines. Active domains are regions of several contiguous amino acids that are necessary for chemokines' ability to suppress the proliferation of actively dividing myeloid cells, e.g., myeloid progenitor cells, myeloid stem cells, and leukemic cells. The new chemokine-like proteins provide higher myelosuppressive activity than naturally occurring, wild-type chemokines.
Abstract: The subject invention pertain to methods of treating Kaposi's Sarcoma and ocular neovascularization using rPF4 and angiogenesis-inhibiting fragments of rPF4.
Abstract: The invention relates to novel chemokine-like proteins that include two or more newly discovered active domains from different chemokines. Active domains are regions of several contiguous amino acids that are necessary for chemokines' ability to suppress the proliferation of actively dividing myeloid cells, e.g., myeloid progenitor cells, myeloid stem cells, and leukemic cells. The new chemokine-like proteins provide higher myelosuppressive activity than naturally occurring, wild-type chemokines.
Abstract: Circulating heparin in a mammal may be neutralized without substantial depletion of platelets or leukocytes by administering to the mammal a heparin neutralizing amount of a purified heparin binding fragment of PF4 or of recombinant PF4.
Abstract: The invention concerns a process for purifying protein A preparations to high purity with high product yield. Where the protein A is obtained from a Gram-negative recombinant microbe hosting a vehicle containing a gene encoding protein A, the protein A is purified to high purity, and, advantageously, to very low levels of endotoxin. The protein A preparations made via the invention process are useful in therapeutic application, e.g., therapeutic plasma exchange, as well as for other well-known uses of protein A.
Abstract: The subject invention concerns a novel treatment for cancer. Specifically, the invention concerns the systemic administration of recombinant Platelet Factor Four (rPF4) to inhibit tumor growth in a mammal having metastatic cancer.
Abstract: Novel recombinant HTLV-III fusion proteins denoted R10, RB1, 590 and the HIV portion of each of these proteins are useful in the diagnosis, prophylaxis or therapy of AIDS. Protein R10 is a 95 kD fusion protein; protein PB1 is a 26 kD fusion protein and protein 590 is an 86 kD fusion protein.
Type:
Grant
Filed:
January 3, 1992
Date of Patent:
November 16, 1993
Assignee:
Repligen Corporation
Inventors:
Scott D. Putney, Debra Lynn, Kashayar Javaherian, William T. Mueller, John Farley
Abstract: The invention concerns unique immobilized immunoglobulin-binding protein materials which have a high binding capacity for immunoglobulins. Exemplified are preparations which have a high binding capacity for IgGl immunoglobulins. The preparations are made by covalently joining an immobilization support material to (a) an arginine-containing linker and (b) an immunoglobulin-binding protein material. The immunoglobulin-binding protein can be joined to the linker through an amide bond. Specifically disclosed is an immobilized protein A preparation. This immobilized protein A preparation has utility in the art of purifying monoclonal antibodies.
Type:
Grant
Filed:
February 18, 1992
Date of Patent:
November 9, 1993
Assignee:
Repligen Corporation
Inventors:
Albert T. Profy, Margaret A. Belew, Walter C. Herlihy
Abstract: Circulating heparin in a mammal may be neutralized without substantial depletion of platelets or leukocytes by administering to the mammal a heparin neutralizing amount of purified PF4 or rPF4 or a heparin neutralizing fragment thereof.
Type:
Grant
Filed:
June 23, 1992
Date of Patent:
April 20, 1993
Assignee:
Repligen Corporation
Inventors:
Jacquelynn J. Cook, Stefan Niewarowski, Theodore E. Maione
Abstract: The gene coding for a protein A-like material has been successfully cloned and expressed for the first time. The cloning of this gene with its nucleotide sequence characterization, also disclosed, enables those skilled in the art to obtain quantities of a protein A-like material nucleotide sequence for cloning in various host-vector systems. Protein A is well known as a valuable component of a variety of diagnostic test systems. The protein A-like material of the subject invention, and subfragments thereof, have the protein A properties of binding to IgG at the Fc region and activation of polyclonal antibody synthesis. Thus, these entities are useful in the same manner as protein A.
Abstract: Novel recombinant HTLV-III fusion proteins denoted R10, PB1, 590, KH1, and the HIV portion of each of these proteins are useful in the diagnosis, prophylaxis or therapy of AIDS. Protein R10 is a 95 kD fusion protein; protein PB1 is a 26 kD fusion protein; protein 590 is an 86 kD fusion protein; and protein KH1 is a 70 kD fusion protein. These proteins are considered to be especially useful to prepare vaccines for the HTLV-III virus.
Type:
Grant
Filed:
September 24, 1990
Date of Patent:
August 25, 1992
Assignee:
Repligen Corporation
Inventors:
Scott D. Putney, Debra Lynn, Kashayar Javaherian, William T. Mueller, John Farley
Abstract: The subject invention pertains to the use of modified PF4 and recombinant PF4(rPF4) as well as modified analogs (mutants) of PF4, and peptide fragments thereof, to inhibit angiogenesis. The modified PF4, analogs, and certain fragments are shown to have utility for treating angiogenic diseases and for the inhibition of endothelial cell proliferation. Also, the subject invention concerns modification of PF4 which facilitate the targeting of the biological activity of PF4 to specific locations.
Abstract: The subject invention is directed to a novel Bacillus thuringiensis kurstaki .delta.-endotoxin prepared by use of a novel hybrid gene. This gene is cloned into a novel plasmid which is transformed into a prokaryotic host. The .delta.-endotoxin of the subject invention is active against Lepidoptera larvae.
Type:
Grant
Filed:
July 27, 1990
Date of Patent:
May 5, 1992
Assignee:
Repligen Corporation
Inventors:
Daniel P. Witt, Donald A. Colbert, Algis Anilionis
Abstract: The invention concerns unique immobilized immunoglobulin-binding protein materials which have a high binding capacity for immunoglobulins. Exemplified are preparations which have a high binding capacity for IgGl immunoglobulins. The preparations are made by covalently joining an immobilization support material to (a) an arginine-containing linker and (b) an immunoglobulin-binding protein material. The immunoglobulin-binding protein can be joined to the linker through an amide bond. Specifically disclosed is an immobilized protein A preparation. This immobilized protein A preparation has utility in the art of purifying monoclonal antibodies.
Type:
Grant
Filed:
March 13, 1987
Date of Patent:
February 18, 1992
Assignee:
Repligen Corporation
Inventors:
Albert T. Profy, Margaret A. Belew, Walter C. Herlihy
Abstract: The subject invention pertains to the use of recombinant PF4 (rPF4) as well as full length novel analogs (mutants) of rPF4, and peptide fragments thereof, to inhibit angiogenesis. rPF4, analogs, and certain fragments are shown to have utility for treating angiogenic diseases and for the inhibition of endothelial cell proliferation.
Abstract: The subject invention concerns novel protein A or protein A-like molecules that can be coupled to other materials through a single, defined site on the protein A molecule. Specifically exemplified is Cysteinyl-rProtein A.TM.. The compounds of the invention, for example, Cysteinyl-rProtein A.TM., can be used in processes wherein protein A is used.
Abstract: The subject invention concerns a novel and superior recombinant DNA expression/secretion system for use in prokaryotic organisms to produce useful proteins. The system can be used to have proteins secreted by an engineered prokaryotic host where normally the proteins are not secreted by the host. Also, when using the expression system, proteins are expressed at much higher levels than when the expression system is not used.
Type:
Grant
Filed:
June 30, 1987
Date of Patent:
September 10, 1991
Assignee:
Repligen Corporation
Inventors:
Joan Petro, Jennifer Jackson, Scott Putney