Title:
HETERODIMERIC FUSION PROTEINS USEFUL FOR TARGETED IMMUNE THERAPY AND GENERAL IMMUNE STIMULATION
Document Type and Number:
WIPO Patent Application WO1999029732
Kind Code:
A3
Abstract:
Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ration of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.
Inventors:
GILLIES STEPHEN D
LO KIN-MING
LAN YAN
LO KIN-MING
LAN YAN
Application Number:
PCT/US1998/025978
Publication Date:
August 26, 1999
Filing Date:
December 08, 1998
Export Citation:
Assignee:
LEXIGEN PHARM CORP (US)
International Classes:
A61K38/00; A61K47/48; A61P37/04; C07K14/54; C07K16/30; C12N15/09; C07K19/00; C12P21/00; (IPC1-7): C07K19/00; A61K38/20; A61K47/48
Domestic Patent References:
| WO1995005468A1 | 1995-02-23 | |||
| WO1996018412A1 | 1996-06-20 | |||
| WO1992008495A1 | 1992-05-29 | |||
| WO1997020062A1 | 1997-06-05 |
Other References:
T. KIM ET AL.: "An ovalbumin-IL-12 fusion protein is more effective than ovalbumin plus free recombinant IL-12 in inducing a T helper cell type 1-dominated immune response and inhibiting antigen-specific IgE production.", THE JOURNAL OF IMMUNOLOGY, vol. 158, no. 9, 1 May 1997 (1997-05-01), Baltimore, MD, USA, pages 4137 - 4144, XP002106573
G. LIESCHKE ET AL.: "Bioactive murine and human interleukin-12 fusion proteins which retain antitumor activity in vivo.", NATURE BIOTECHNOLOGY, vol. 15, no. 1, January 1997 (1997-01-01), New York, NY, USA, pages 35 - 40, XP002106574
M. MARK ET AL.: "Expression and charaxcterization of hepatocyte growth factor receptor-IgG fusion proteins.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 267, no. 36, 25 December 1992 (1992-12-25), Baltimore, MD, USA, pages 26166 - 26171, XP002106575
S. GILLIES ET AL.: "Antibody-IL-12 fusion proteins are effective in SCID mouse models of prostate and colon carcinoma metastases.", THE JOURNAL OF IMMUNOLOGY, vol. 160, no. 12, 15 June 1998 (1998-06-15), Baltimore, MD, USA, pages 6195 - 6203, XP002106576
G. LIESCHKE ET AL.: "Bioactive murine and human interleukin-12 fusion proteins which retain antitumor activity in vivo.", NATURE BIOTECHNOLOGY, vol. 15, no. 1, January 1997 (1997-01-01), New York, NY, USA, pages 35 - 40, XP002106574
M. MARK ET AL.: "Expression and charaxcterization of hepatocyte growth factor receptor-IgG fusion proteins.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 267, no. 36, 25 December 1992 (1992-12-25), Baltimore, MD, USA, pages 26166 - 26171, XP002106575
S. GILLIES ET AL.: "Antibody-IL-12 fusion proteins are effective in SCID mouse models of prostate and colon carcinoma metastases.", THE JOURNAL OF IMMUNOLOGY, vol. 160, no. 12, 15 June 1998 (1998-06-15), Baltimore, MD, USA, pages 6195 - 6203, XP002106576
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