Human Granulocyte-Macrophage Colony Stimulating Factor
Award last edited on: 11/26/02

Sponsored Program
Awarding Agency
Total Award Amount
Award Phase
Solicitation Topic Code

Principal Investigator
Frederick Hagen

Company Information

Zymogenetics Inc

1201 Eastlake Avenue East
Seattle, WA 98102
   (206) 442-6600
Location: Single
Congr. District: 07
County: King

Phase I

Contract Number: 1R43AI022772-01
Start Date: 00/00/00    Completed: 00/00/00
Phase I year
Phase I Amount
The goal of the project is the development of a commercially feasible system for the production of human granulocyte-macrophage colony stimulating factor (GmCSF) for use as a therapeutic agent in the treatment of patients whose immune system has been suppressed as a result of treatment with radiation therapy or chemotherapeutic agents. In Phase I the DNA coding sequence for GmCSF will be cloned and expressed in a mammalian cell culture system. The GmCSF cDNA will be obtained by screening cDNA libraries with oligonucleotide probes designed from the published sequence of murine GmCSF or by screening a phage expression cDNA library with radiolabeled GmCSF an tibody. Oligonucleotides or nick translated cDNA probes will be used to obtain the genomic GmCSF DNA. From the cDNA and/or genomic DNA, a coding sequence for GmCSF will be assembled. This sequence will be expressed as biologically active GmCSF in tissue culture cells. Expression of biologically active GmCSF will provide information for determining the feasibility of obtaining production level expression in Phase II. The anticipated use of GmCSF will be to enhance the proliferation of granulocytes and macrophage in immune suppressed patients, thereby providing an innovative approach in combination with conventional cell replacement or antibiotic therapy.National Institute of Allergy and Infectious Diseases (NIAID)

Phase II

Contract Number: 2R44AI022772-02A1
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
(last award dollars: 1988)
Phase II Amount

Human granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor that primarily stimulates the growth and development of granulocytes and macrophages and, of less certain significance, platelets and red blood cell precursors in vitro. GM-CSF has also been shown to have similar effects on hematopoiesis in primate model systems. This suggests a potential for clinical use in stimulating the more rapid return of white blood cell levels to normal in patients treated with chemotherapy.Currently, a proprietary system for the production of GM-CSF in filamentous fungus is being used to produce GM-CSF. The efficacy of the native, carbohydrate-free GM-CSF produced in this system will be compared to rGM-CSF made by mammalian cells in a primate model system. This model system will be used to determine the role of carbohydrate in the circulatory half-life, antigenicity, toxicity, and efficacy of GM-CSF. Different portions of the amino acid sequence of GM-CSF will also be tested to determine whether a subset or altered-sequence form of GM-CSF may be developed that would be a more effective therapeutic agent. Expression of GM-CSF will be optimized to commercial production levels, and a large-scale purification scheme will be developed.National Institute of Allergy and Infectious Diseases (NIAID)