[go: up one dir, main page]

WO1996008274A3 - Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents - Google Patents

Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents Download PDF

Info

Publication number
WO1996008274A3
WO1996008274A3 PCT/US1995/012205 US9512205W WO9608274A3 WO 1996008274 A3 WO1996008274 A3 WO 1996008274A3 US 9512205 W US9512205 W US 9512205W WO 9608274 A3 WO9608274 A3 WO 9608274A3
Authority
WO
WIPO (PCT)
Prior art keywords
growth factor
conjugates
heparin
targeted
binding epidermal
Prior art date
Application number
PCT/US1995/012205
Other languages
French (fr)
Other versions
WO1996008274A2 (en
Inventor
Barbara A Sosnowski
Lois Ann Chandler
L L Houston
Michael P Nova
John R Mcdonald
Original Assignee
Prizm Pharma Inc
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 Prizm Pharma Inc filed Critical Prizm Pharma Inc
Priority to AU37244/95A priority Critical patent/AU3724495A/en
Publication of WO1996008274A2 publication Critical patent/WO1996008274A2/en
Publication of WO1996008274A3 publication Critical patent/WO1996008274A3/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/168Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0042Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/642Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6425Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/415Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475Growth factors; Growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475Growth factors; Growth regulators
    • C07K14/50Fibroblast growth factor [FGF]
    • C07K14/503Fibroblast growth factor [FGF] basic FGF [bFGF]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/04Fusion polypeptide containing a localisation/targetting motif containing an ER retention signal such as a C-terminal HDEL motif
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/20Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/50Fusion polypeptide containing protease site
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/55Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/70Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/80Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00Uses of viruses
    • C12N2799/02Uses of viruses as vector
    • C12N2799/021Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/026Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Wood Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Cell Biology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Conjugates of heparin-binding epidermal growth factor-like growth factor (HBEGF) linked, either directly or via a linker, to a targeted agent are provided. The targeted agent is a cytotoxic agent, such as a ribosome-inactivating protein (RIP) and an antisense nucleic acid, or is a therapeutic nucleic acid for targeted delivery. The targeted agent is attached to HBEGF, or via a linker, through a chemical bond, or the conjugate is prepared as a chimera using techniques of recombinant DNA. The conjugates are used to target cytotoxic agents or therapeutic nucleotides to cells bearing EGF receptors and are particularly useful for treating solid tumors, such as breast and bladder tumors, and for treating disorders involving pathophysiological proliferation of smooth muscle cells, such as restenosis.
PCT/US1995/012205 1994-09-13 1995-09-13 Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents WO1996008274A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU37244/95A AU3724495A (en) 1994-09-13 1995-09-13 Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US30577194A 1994-09-13 1994-09-13
US08/305,771 1994-09-13
US44197995A 1995-05-16 1995-05-16
US08/441,979 1995-05-16

Publications (2)

Publication Number Publication Date
WO1996008274A2 WO1996008274A2 (en) 1996-03-21
WO1996008274A3 true WO1996008274A3 (en) 1996-04-04

Family

ID=26974775

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/012205 WO1996008274A2 (en) 1994-09-13 1995-09-13 Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents

Country Status (2)

Country Link
AU (1) AU3724495A (en)
WO (1) WO1996008274A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7192736B2 (en) 1998-07-22 2007-03-20 Osprey Pharmaceuticals, Ltd. Nucleic acid molecules encoding cytotoxic conjugates that contain a chemokine receptor targeting agent

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6037329A (en) * 1994-03-15 2000-03-14 Selective Genetics, Inc. Compositions containing nucleic acids and ligands for therapeutic treatment
CA2221269A1 (en) * 1995-05-16 1996-11-21 Lois A. Chandler Compositions containing nucleic acids and ligands for therapeutic treatment
AU717277B2 (en) 1995-10-23 2000-03-23 Children's Medical Center Corporation Therapeutic antiangiogenic compositions and methods
JP2002515784A (en) * 1996-06-24 2002-05-28 セレクティブ ジェネティクス,インコーポレイテッド Heparin-treated medical device containing heparin-binding growth factor conjugate
US6838238B1 (en) * 1996-10-17 2005-01-04 Invitrogen Corporation Morphatides: novel shape and structure libraries
EP1075271A4 (en) * 1998-04-17 2002-09-25 Univ Maryland METHOD FOR TREATING INTERSTITIAL BLADDER INFLAMMATION WITH RECOMBINANT HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR (HB-EGF)
US7060433B1 (en) 1999-11-12 2006-06-13 Rigel Pharmaceuticals, Inc. Methods and compositions for screening using diphtheria toxin constructs
WO2001019989A2 (en) * 1999-09-14 2001-03-22 Entremed, Inc. Method of producing and purifying endostatintm protein
WO2001034806A2 (en) * 1999-11-12 2001-05-17 Rigel Pharmaceuticals, Inc. Methods and compositions for screening using diphtheria toxin constructs
FR2805821B1 (en) * 2000-03-01 2004-01-16 Diatos AMINO ACID SEQUENCES TO FACILITATE THE PENETRATION OF A SUBSTANCE OF INTEREST WITHIN CELLS AND / OR CELL CORES
US8003595B2 (en) 2000-03-01 2011-08-23 Cellectis Amino acid sequences facilitating penetration of a substance of interest into cells and/or cell nuclei
WO2004096254A2 (en) * 2003-05-02 2004-11-11 Xpression Antibody Therapeutics, Inc. Transferrin conjugates for tumor treatment
WO2004096117A2 (en) * 2003-05-02 2004-11-11 Xpression Antibody Therapeutics, Inc. Drug delivery systems comprising transferrin-nucleic acid conjugates
AU2004265159B2 (en) 2003-08-14 2010-08-19 Cellectis Amino acid sequences facilitating penetration of a substance of interest into cells and/or cell nuclei
WO2005033134A2 (en) * 2003-09-30 2005-04-14 Regeneron Pharmaceuticals, Inc. Secreted protein therapeutics and uses thereof
GB0718045D0 (en) 2007-09-14 2007-10-24 Peptcell Ltd Pharmaceutical compound
US9790264B2 (en) 2012-06-25 2017-10-17 The Brigham And Women's Hospital, Inc. Compounds and methods for modulating pharmacokinetics
CN104619727B (en) * 2012-06-25 2019-04-05 布里格姆及妇女医院股份有限公司 Targeted therapy
CN116390932A (en) * 2020-06-24 2023-07-04 萨普雷米科技有限公司 Saponin derivative for use in medicine
US20240115726A1 (en) * 2020-06-24 2024-04-11 Sapreme Technologies B.V. Hydrazone-based saponin derivatives

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992006705A1 (en) * 1990-10-16 1992-04-30 The Children's Medical Center Corporation Heparin binding mitogen with homology to epidermal growth factor (egf)
WO1993025688A1 (en) * 1992-06-16 1993-12-23 Whittier Institute For Diabetes And Endocrinology Recombinant production of saporin-containing proteins
WO1995003831A1 (en) * 1993-08-02 1995-02-09 Prizm Pharmaceuticals, Inc. Monogenous preparations of cytotoxic conjugates
WO1995024928A2 (en) * 1994-03-15 1995-09-21 Prizm Pharmaceuticals, Inc. Heparin-binding growth factors for gene therapy and anterior eye disorders

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992006705A1 (en) * 1990-10-16 1992-04-30 The Children's Medical Center Corporation Heparin binding mitogen with homology to epidermal growth factor (egf)
WO1993025688A1 (en) * 1992-06-16 1993-12-23 Whittier Institute For Diabetes And Endocrinology Recombinant production of saporin-containing proteins
WO1995003831A1 (en) * 1993-08-02 1995-02-09 Prizm Pharmaceuticals, Inc. Monogenous preparations of cytotoxic conjugates
WO1995024928A2 (en) * 1994-03-15 1995-09-21 Prizm Pharmaceuticals, Inc. Heparin-binding growth factors for gene therapy and anterior eye disorders

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
CHANDLER L. A. ET AL.: "CHARACTERIZATION OF MITOTOXINS CONTAING HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR FUSED TO SAPORIN.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL MEETING, vol. 36, no. 0, pages 425 *
CHEMICAL ABSTRACTS, vol. 121, no. 23, 5 December 1994, Columbus, Ohio, US; abstract no. 271455, MESRI, ENRIQUE A. ET AL: "The heparin-binding domain of heparin-binding EGF-like growth factor can target Pseudomonas exotoxin to kill cells exclusively through heparan sulfate proteoglycans" *
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; *
E. A. MESRI ET AL.: "HEPARIN-BINDING TRANSFORMING GROWTH FACTOR ALPHA-PSEUDOMONAS EXOTOXIN A.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 7, 5 March 1993 (1993-03-05), MD US, pages 4853 - 4862, XP000578211 *
EIGHTY-SIXTH ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, TORONTO,CANADA., 18 March 1995 (1995-03-18) - 22 March 1995 (1995-03-22) *
J. CELL SCI. (1994), 107(9), 2599-608 CODEN: JNCSAI;ISSN: 0021-9533 *
MICHAEL WESTBY ET AL.: "PREPARATION AND CHARACTERIZATION OF RECOMBINANT PRORICIN CONTAINING AN ALTERNATIVE PROTEASE-SENSITIVE LINKER SEQUENCE.", BIOCONJUGATE CHEMISTRY, vol. 3, WASHINGTON US, pages 375 - 381, XP002187830 *
S. A. THOMPSON ET AL.: "CHARACTERIZATION OF SEQUENCES WITHIN HEPARIN-BINDING EGF-LIKE GROWTH FACTOR THAT MEDIATE INTERACTION WITH HEPARIN.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 4, 28 January 1994 (1994-01-28), MD US, pages 2541 - 2549, XP000578210 *
ZHOU FEN ET AL.: "STRUCTURAL ORGANIZATION AND CHROMOSOMAL ASSIGNEMNET OF THE GEN ENCODING THE HUMAN HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR/DIPHTHERIA TOXIN RECEPTOR.", BIOCHEMISTRY, vol. 32, EASTON, PA US, pages 7932 - 7938 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7192736B2 (en) 1998-07-22 2007-03-20 Osprey Pharmaceuticals, Ltd. Nucleic acid molecules encoding cytotoxic conjugates that contain a chemokine receptor targeting agent

Also Published As

Publication number Publication date
WO1996008274A2 (en) 1996-03-21
AU3724495A (en) 1996-03-29

Similar Documents

Publication Publication Date Title
WO1996008274A3 (en) Conjugates of heparin-binding epidermal growth factor-like growth factor with targeted agents
EP0259904B1 (en) Advanced anticancer therapy and cytotoxic medicaments for its implementation
US5502037A (en) Pro-cytotoxic drug conjugates for anticancer therapy
EP0699766A1 (en) Therapeutic antibody based fusion proteins with platelet factor-4
US7807134B2 (en) Multidrug multiligand conjugates for targeted drug delivery
ZA958444B (en) Biological active proteins
EP0954340A4 (en) Targeted combination immunotherapy of cancer
CA2053275A1 (en) Fibroblast Growth Factor Conjugates
WO1988005077A1 (en) A method of modifiying the metabolism of eukaryotic cells upon incorporation therein of foreign sequences of nucleic acids by means of an internalizing vector
IL187388A0 (en) Use of a conjugate for preparing a composition for treating secondary tissue damage and other inflammatory conditions
WO1998051325A3 (en) Random peptides that bind to gastro-intestinal tract (git) transport receptors and related methods
ES2060947T3 (en) A NEW ANTIBODY SUPPLY SYSTEM FOR BIOLOGICAL RESPONSE MODIFIERS.
ES2193143T3 (en) USE OF IMMUNOCONJUGADOS FOR THE DIAGNOSIS AND / OR THERAPY OF VASCULARIZA TUMORS.
WO1999048536A3 (en) Delivery of long lasting therapeutic agents by forming covalent attachments in vivo
AU6721998A (en) Therapeutic use of the smr1 protein and active derivatives thereof
WO2002087497A3 (en) Therapeutic agent/ligand conjugate compositions, their methods of synthesis and use
WO1997048804A3 (en) Tie-2 receptor ligands (tie ligand-3; tie ligand-4) and their uses
Mickisch et al. Pseudomonas exotoxin conjugated to monoclonal antibody MRK16 specifically kills multidrug resistant cells in cultured renal carcinomas and in MDR-transgenic mice
US7368431B2 (en) Polypeptide, the conjugate thereof with doxorubicine and a pharmaceutical composition based thereon
WO2001036005A3 (en) Targeted delivery of therapeutic and diagnostic moieties
WO2001008708A3 (en) Enhanced delivery via serpin enzyme complex receptor ligands
CN109152845B (en) Comprising at least two (-CH) s within a ring2-CH2Conjugates of linkers of-O-) units and conjugation reagents
Okamoto et al. Expression of fibroblast growth factor binding protein HBp17 in normal and tumor cells
Tsuruo et al. Enhanced cytocidal action of methotrexate by conjugation to concanavalin A
JP2005508875A5 (en)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AM AU BB BG BR BY CA CN CZ EE FI GE HU IS JP KG KP KR KZ LK LR LT LV MD MG MN MX NO NZ PL RO RU SG SI SK TJ TM TT UA UZ VN

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

CFP Corrected version of a pamphlet front page
CR1 Correction of entry in section i

Free format text: PAT.BUL.13/96 UNDER INID(54)"TITLE",REPLACE THE EXISTING TEXT BY"CONJUGATES OF HEPARIN-BINDING EPIDERMIAL GROWTH FACTOR-LIKE GROWTH FACTOR WITH TARGETED AGENTS"

AK Designated states

Kind code of ref document: A3

Designated state(s): AM AU BB BG BR BY CA CN CZ EE FI GE HU IS JP KG KP KR KZ LK LR LT LV MD MG MN MX NO NZ PL RO RU SG SI SK TJ TM TT UA UZ VN

Kind code of ref document: A3

Designated state(s): AM AU BB BG BR BY CA CN CZ EE FI GE HU IS JP KG KP KR KZ LK LR LT LV MD MG MN MX NO NZ PL RO RU SG SI SK TJ TM TT UA UZ KE

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)