CA2072891A1 - Pseudomonas exotoxin fusion proteins having carboxyl alterations with increased cytotoxicity - Google Patents

Pseudomonas exotoxin fusion proteins having carboxyl alterations with increased cytotoxicity

Info

Publication number
CA2072891A1
CA2072891A1 CA2072891A CA2072891A CA2072891A1 CA 2072891 A1 CA2072891 A1 CA 2072891A1 CA 2072891 A CA2072891 A CA 2072891A CA 2072891 A CA2072891 A CA 2072891A CA 2072891 A1 CA2072891 A1 CA 2072891A1
Authority
CA
Canada
Prior art keywords
carboxyl
pseudomonas exotoxin
alterations
fusion proteins
increased cytotoxicity
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA2072891A
Other languages
French (fr)
Other versions
CA2072891C (en
Inventor
Ira Pastan
Vijay Chaudhary
David J. Fitzgerald
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
US Department of Health and Human Services
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2072891A1 publication Critical patent/CA2072891A1/en
Application granted granted Critical
Publication of CA2072891C publication Critical patent/CA2072891C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/21—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Pseudomonadaceae (F)
    • 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
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/495—Transforming growth factor [TGF]
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70514—CD4
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/034—Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the periplasmic space of Gram negative bacteria as a soluble protein, i.e. signal sequence should be cleaved
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A target-specific, cytotoxic, recombinant Pseudomonas exotoxin is described.
Such toxins are made by inserting specific recognition molecules at specific cloning sites in at least domain III at the carboxyl terminus of the PE molecule. Various modifications of the carboxyl terminus of the PE molecule to increase cyotoxicity are set forth.
CA002072891A 1990-01-02 1990-12-27 Pseudomonas exotoxin fusion proteins having carboxyl alterations with increased cytotoxicity Expired - Fee Related CA2072891C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US45963590A 1990-01-02 1990-01-02
US459,635 1990-01-02
PCT/US1990/007421 WO1991009949A1 (en) 1990-01-02 1990-12-27 Target-specific, cytotoxic, recombinant pseudomonas exotoxin

Publications (2)

Publication Number Publication Date
CA2072891A1 true CA2072891A1 (en) 1991-07-03
CA2072891C CA2072891C (en) 1999-12-21

Family

ID=23825594

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002072891A Expired - Fee Related CA2072891C (en) 1990-01-02 1990-12-27 Pseudomonas exotoxin fusion proteins having carboxyl alterations with increased cytotoxicity

Country Status (5)

Country Link
EP (1) EP0509056A4 (en)
JP (1) JP2610740B2 (en)
AU (1) AU644139B2 (en)
CA (1) CA2072891C (en)
WO (1) WO1991009949A1 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU631200B2 (en) * 1989-02-17 1992-11-19 Merck & Co., Inc. Production of modified pe40
US5458878A (en) * 1990-01-02 1995-10-17 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services P. exotoxin fusio proteins have COOHG220101al alterations which increase cytotoxicity
NZ237758A (en) * 1990-04-17 1992-12-23 Shell Int Research (phenylalkyl) triphenylphosphonium salt derivatives and fungicidal compositions
ATE182175T1 (en) * 1990-05-11 1999-07-15 Us Health IMPROVED EXOTOXINS FROM PSEUDOMONAS WITH LOW TOXICITY IN ANIMAL AND HIGH CELL KILLING ACTIVITY
EP1635868A1 (en) 2003-04-30 2006-03-22 Uwe Zangemeister-Wittke Methods for treating cancer using an immunotoxin
US8932586B2 (en) 2011-09-06 2015-01-13 Intrexon Corporation Modified forms of Pseudomonas exotoxin A
WO2016146833A1 (en) 2015-03-19 2016-09-22 F. Hoffmann-La Roche Ag Biomarkers for nad(+)-diphthamide adp ribosyltransferase resistance
EP3184547A1 (en) 2015-10-29 2017-06-28 F. Hoffmann-La Roche AG Anti-tpbg antibodies and methods of use

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4545985A (en) * 1984-01-26 1985-10-08 The United States Of America As Represented By The Secretary, Dept. Of Health And Human Services Pseudomonas exotoxin conjugate immunotoxins
US4892827A (en) * 1986-09-24 1990-01-09 The United States Of America As Represented By The Department Of Health And Human Services Recombinant pseudomonas exotoxins: construction of an active immunotoxin with low side effects
US5458878A (en) * 1990-01-02 1995-10-17 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services P. exotoxin fusio proteins have COOHG220101al alterations which increase cytotoxicity

Also Published As

Publication number Publication date
CA2072891C (en) 1999-12-21
AU644139B2 (en) 1993-12-02
JP2610740B2 (en) 1997-05-14
EP0509056A4 (en) 1993-02-17
JPH05502032A (en) 1993-04-15
WO1991009949A1 (en) 1991-07-11
AU7242491A (en) 1991-07-24
EP0509056A1 (en) 1992-10-21

Similar Documents

Publication Publication Date Title
CA2082824A1 (en) Pseudomonas exotoxin multifunctional fusion proteins having carboxyl alterations with increased cytotoxicity
GR3033553T3 (en) Site-specific conjugation of immunoglobulins and detectable labels.
CA2072891A1 (en) Pseudomonas exotoxin fusion proteins having carboxyl alterations with increased cytotoxicity
CA2095797A1 (en) Arylacetamides
CA2168011A1 (en) Hybrid toxin
DE69112089D1 (en) Elastic, voluminous fiber obtained by cross-linking wood pulp fibers with polycarboxylic acids.
DE68924030D1 (en) Modified aqueous phenoxy resins.
AU7988294A (en) Process for heating an asphalt surface
ES484783A0 (en) PROCEDURE TO OBTAIN IMPROVED MOLDABLE MASSES.
CA2075974A1 (en) Totally synthetic affinity reagents
CA2031118A1 (en) Direction dependent line light source
EP0823456A4 (en) Polyacetal resin composition
EP0827749A3 (en) Peritoneal dialysis solution
CA2133834A1 (en) Process for preparing modified proteins
NZ232564A (en) Pseudomonas exotoxin a, pe40 domain derivatives conjugated to a protein targeting domain
AU5108798A (en) Polyacrylamide gel matrix
AU591077B2 (en) Prolonged-action immunotoxins containing a glycopeptide constituent which inactivates ribosomes, modified on its polysaccharide units
Siehnel et al. Function and structure of the porin proteins OprF and OprP of Pseudomonas aeruginosa.
EP0439048A3 (en) Monoclonal antibody recognizing anthracycline glycoside specific epitope and hybridoma secerning said antibody
ITTO911040A1 (en) FUEL TANK FOR MOTOR VEHICLES AND PROCEDURE FOR ITS REALIZATION.
CA2102859A1 (en) Expression Vector for Phytolacca Antiviral Protein
ITTO911054A0 (en) VEHICLE WITH BODYWORK THAT CAN BE CONVERTED FROM A COUPE TO A SPIDER.
DE69001957D1 (en) POLYSACCHARIDE FACTION WITH AN EFFECT AGAINST HIV.
CA2136239A1 (en) Leukotriene c4 synthase
KR920007867A (en) Automotive Bumper

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed