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Patent No. 5453361 Method for producing biologically active human brain derived neurotrophic factor

 

Patent No. 5453361

Method for producing biologically active human brain derived neurotrophic factor (Yancopoulos, et al., Sep 26, 1995)

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.

Notes:

SUMMARY OF THE INVENTION

The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), to the substantially pure protein, peptide fragments or derivatives produced in quantity therefrom, and to antibodies directed toward BDNF protein, peptide fragments, or derivatives. The present invention makes available, for the first time, sufficient quantities of BDNF to enable anti-BDNF antibody production and to support diagnostic and therapeutic applications of BDNF.

In various embodiments of the invention, the BDNF nucleic acids, proteins, peptides, derivatives, or antibodies of the invention may be utilized in methods for the diagnosis and treatment of a variety of neurologic diseases and disorders, and, in particular, in the diagnosis and treatment of sensory neuron disorders and retinal degeneration. Furthermore, in specific embodiments of the invention, BDNF nucleic acids or BDNF gene products may be used in the diagnosis and treatment of neuroblastoma tumor, Parkinson's disease, and Alzheimer's disease. BDNF gene products may also be used to facilitate incorporation of implants into nervous tissue or, alternatively, to promote nerve regeneration following damage by trauma, infarction, infection, or post-operatively, in additional specific embodiments of the invention.

The invention also relates to pharmaceutical compositions comprising effective amounts of BDNF gene products or, alternatively, antibodies directed toward BDNF gene products, which may be utilized in the diagnosis or treatment of a variety of neurological diseases and disorders.

In addition, by providing the full nucleotide sequence of BDNF, the present invention allows for the comparison of BDNF and NGF genes, thereby identifying homologous regions and defining a BDNF/NGF gene family. Accordingly, the present invention relates to a method for identifying additional members of the BDNF/NGF gene family. In a specific embodiment, the method of the invention is used to identify a novel, non-NGF, non-BDNF member of the BDNF/NGF gene family. The invention further provides for additional members of the BDNF/NGF gene family identified according to the disclosed method and to their gene products.

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