WO1999029732A3 - Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation - Google Patents

Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation Download PDF

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Publication number
WO1999029732A3
WO1999029732A3 PCT/US1998/025978 US9825978W WO9929732A3 WO 1999029732 A3 WO1999029732 A3 WO 1999029732A3 US 9825978 W US9825978 W US 9825978W WO 9929732 A3 WO9929732 A3 WO 9929732A3
Authority
WO
WIPO (PCT)
Prior art keywords
fusion proteins
fused
subunit
fusion protein
proteins useful
Prior art date
Application number
PCT/US1998/025978
Other languages
French (fr)
Other versions
WO1999029732A2 (en
Inventor
Stephen D Gillies
Kin-Ming Lo
Yan Lan
Original Assignee
Lexigen Pharm Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lexigen Pharm Corp filed Critical Lexigen Pharm Corp
Priority to EP98961978A priority Critical patent/EP1037927B1/en
Priority to CA2312188A priority patent/CA2312188C/en
Priority to JP2000524321A priority patent/JP4336452B2/en
Priority to DE69824039T priority patent/DE69824039T2/en
Priority to AT98961978T priority patent/ATE267215T1/en
Priority to AU17160/99A priority patent/AU763719B2/en
Publication of WO1999029732A2 publication Critical patent/WO1999029732A2/en
Publication of WO1999029732A3 publication Critical patent/WO1999029732A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5434—IL-12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

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.
PCT/US1998/025978 1997-12-08 1998-12-08 Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation WO1999029732A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP98961978A EP1037927B1 (en) 1997-12-08 1998-12-08 Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation
CA2312188A CA2312188C (en) 1997-12-08 1998-12-08 Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation
JP2000524321A JP4336452B2 (en) 1997-12-08 1998-12-08 Dimeric fusion proteins useful for targeted immunotherapy and general immune stimulation
DE69824039T DE69824039T2 (en) 1997-12-08 1998-12-08 HETERODIMARY FUSION PROTEINS FOR THE USE OF TARGETED IMMUNOTHERAPY AND GENERAL IMMUNE REGION
AT98961978T ATE267215T1 (en) 1997-12-08 1998-12-08 HETERODIMARY FUSION PROTEINS FOR USE FOR TARGETED IMMUNTHERAPY AND GENERAL IMMUNE EXCITATION
AU17160/99A AU763719B2 (en) 1997-12-08 1998-12-08 Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US98699797A 1997-12-08 1997-12-08
US08/986,997 1997-12-08

Publications (2)

Publication Number Publication Date
WO1999029732A2 WO1999029732A2 (en) 1999-06-17
WO1999029732A3 true WO1999029732A3 (en) 1999-08-26

Family

ID=25532973

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/025978 WO1999029732A2 (en) 1997-12-08 1998-12-08 Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation

Country Status (11)

Country Link
US (4) US6838260B2 (en)
EP (2) EP1489100B1 (en)
JP (2) JP4336452B2 (en)
AT (1) ATE267215T1 (en)
AU (1) AU763719B2 (en)
CA (2) CA2693296C (en)
DE (1) DE69824039T2 (en)
DK (1) DK1037927T3 (en)
ES (2) ES2221717T3 (en)
PT (1) PT1037927E (en)
WO (1) WO1999029732A2 (en)

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US8691952B2 (en) 2005-12-30 2014-04-08 Merck Patent Gmbh Anti-CD19 antibodies with reduced immunogenicity
US8835606B2 (en) 2004-01-22 2014-09-16 Merck Patent Gmbh Anti-cancer antibodies with reduced complement fixation

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