Abstract: Heterodimer proteins comprising a soluble .alpha. specificity determining cytokine receptor component and the extracellular domain of a .beta. receptor component function as CNTF and IL-6 antagonsists.
Type:
Grant
Filed:
October 20, 1993
Date of Patent:
November 28, 1995
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Neil Stahl, Aris N. Economides, George D. Yancopoulos
Abstract: The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen. Further, by permitting a comparison of the nucleic acid sequences of BDNF and NGF, the present invention provides for the identification of homologous regions of nucleic acid sequence between BDNF and NGF, thereby defining a BDNF/NGF gene family; the invention provides a method for identifying and isolating additional members of this gene family.
Type:
Grant
Filed:
January 21, 1992
Date of Patent:
September 26, 1995
Assignees:
Regeneron Pharmaceuticals, Inc., Max Plank Gesselschaft zur Forderung der Wissenschaften
Inventors:
George Yancopoulos, Yves-Alain Barde, Hans Thoenen, Friedrich Lottspeich, Joachim Leibrock
Abstract: The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. In a specific embodiment, BDNF may be used to promote the survival of substantia nigra dopaminergic neurons and basal forebrain cholinergic neurons, thereby providing a method for treating, respectively, Parkinson's disease and Alzheimer's disease. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen.
Type:
Grant
Filed:
April 25, 1991
Date of Patent:
August 1, 1995
Assignees:
Max-Planck-Gesellschaft zur Foderund der Wissenschaften e.V., Regeneron Pharmaceuticals, Inc.
Inventors:
Yves-Alain Barde, Joachim Leibrock, Friedrich Lottspeich, David Edgar, George Yancopoulos, Hans Thoenen
Abstract: The present invention relates to the ciliary neurotrophic factor (CNTF) receptor, and provides for CNTF receptor nucleic acid and amino acid sequences. It also relates to (i) assay systems for detecting CNTF activity; (ii) experimental model systems for studying the physiologic role of CNTF; (ii) diagnostic techniques for identifying CNTF-related neurologic conditions; (iv) therapeutic techniques for the treatment of CNTF-related neurologic and muscular conditions, and (v) methods for identifying molecules homologous to CNTF and CNTFR.
Type:
Grant
Filed:
March 28, 1991
Date of Patent:
June 20, 1995
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Samuel Davis, Stephen P. Squinto, Mark E. Furth, George D. Yancopoulos
Abstract: Signal sequences based on LamB have been constructed. These signal sequences facilitate both the synthesis and secretion of neurotrophins in E. coli.
Abstract: An assay system useful for detecting denervated or degenerating muscle by measuring the amount of soluble ciliary neurotrophic factor receptor in body fluids is described.
Type:
Grant
Filed:
July 2, 1992
Date of Patent:
November 1, 1994
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Nancy Y. Ip, Peter S. DiStefano, Neil Stahl
Abstract: The present invention provides for a stable, biologically active CNTF/receptor complex, and hybrids or routants thereof. The invention is also based in part on the discovery that the CNTF/receptor complex promotes differentiation through a signal transduction pathway on target cells that do not express the CNTF receptor. The invention further provides for a specific CNTFR mutant that promotes signal transduction without binding CNTF. The invention also provides for a CNTF/receptor blocking mutant, a mutant possessing a high binding affinity to CNTF, but possessing no signal transducing function. The present invention also identifies receptor components shared by the IL-6, CNTF, LIF and OSM signal transduction pathways, and the initiation of signal transduction based upon the presence of such components.
Abstract: DNA plasmid expression vector, pCMX, enables cDNA expression cloning in mammalian cell culture. This novel expression vector exhibits a marked increase in gene expression when compared to its parental plasmid construction.
Abstract: The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. In a specific embodiment, BDNF may be used to promote the survival of substantia nigra dopaminergic neurons and basal forebrain cholinergic neurons, thereby providing a method for treating, respectively, Parkinson's disease and Alzheimer's disease. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen.
Type:
Grant
Filed:
August 20, 1990
Date of Patent:
July 20, 1993
Assignees:
Regeneron Pharmaceuticals, Inc., Max Planck Gesellschaft
Inventors:
Yves-Alain Barde, Joachim Leibrock, Friedrich Lottspeich, David Edgar, George Yancopoulos, Hans Thoenen
Abstract: The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors.
Type:
Grant
Filed:
August 8, 1990
Date of Patent:
December 8, 1992
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Eric M. Shooter, Ulrich Suter, Nancy Ip, Stephen P. Squinto, Mark E. Furth, Ronald M. Lindsay, George D. Yancopoulos