WO1998033528A3 - Induction of b cell tolerance - Google Patents

Induction of b cell tolerance Download PDF

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Publication number
WO1998033528A3
WO1998033528A3 PCT/US1998/002103 US9802103W WO9833528A3 WO 1998033528 A3 WO1998033528 A3 WO 1998033528A3 US 9802103 W US9802103 W US 9802103W WO 9833528 A3 WO9833528 A3 WO 9833528A3
Authority
WO
WIPO (PCT)
Prior art keywords
compositions
galα1
xenograft
cells
provides methods
Prior art date
Application number
PCT/US1998/002103
Other languages
French (fr)
Other versions
WO1998033528A9 (en
WO1998033528A2 (en
Inventor
Aron Thall
Original Assignee
Biotransplant 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 Biotransplant Inc filed Critical Biotransplant Inc
Priority to JP53321498A priority Critical patent/JP2001518074A/en
Priority to CA002279544A priority patent/CA2279544A1/en
Priority to AU63191/98A priority patent/AU6319198A/en
Priority to EP98907366A priority patent/EP0969872A2/en
Publication of WO1998033528A2 publication Critical patent/WO1998033528A2/en
Publication of WO1998033528A3 publication Critical patent/WO1998033528A3/en
Publication of WO1998033528A9 publication Critical patent/WO1998033528A9/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/56—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/56—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6819—Plant toxins
    • A61K47/6825—Ribosomal inhibitory proteins, i.e. RIP-I or RIP-II, e.g. Pap, gelonin or dianthin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/68—Medicinal 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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal 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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal 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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Botany (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Optical Measuring Cells (AREA)
  • Magnetic Record Carriers (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention provides methods and compositions for promoting in a first species a state of tolerance against Galα1,3Gal epitopes present on a xenograft from a second species, thereby preventing hyperacute rejection (HAR) of the xenograft. The methods and compositions according to the invention cause the elimination or anergy of specific lymphoid according cells which are responsible for the production of xenoreactive natural antibodies (XNAs) which cause HAR of the xenograft. In a first aspect, the invention provides methods and tolerogenic compositions for inducing anergy in B cells which are specific for the Galα1,3Gal epitope. In a second aspect, the invention provides methods and tolerogenic compositions for inducing apoptosis in B cells specific for the Galα1,3Gal epitope.
PCT/US1998/002103 1997-02-05 1998-02-05 Induction of b cell tolerance WO1998033528A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP53321498A JP2001518074A (en) 1997-02-05 1998-02-05 Induction of B cell tolerance
CA002279544A CA2279544A1 (en) 1997-02-05 1998-02-05 Induction of b cell tolerance
AU63191/98A AU6319198A (en) 1997-02-05 1998-02-05 Induction of b cell tolerance
EP98907366A EP0969872A2 (en) 1997-02-05 1998-02-05 Induction of b cell tolerance

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US79592597A 1997-02-05 1997-02-05
US08/795,925 1997-02-05

Publications (3)

Publication Number Publication Date
WO1998033528A2 WO1998033528A2 (en) 1998-08-06
WO1998033528A3 true WO1998033528A3 (en) 1999-02-11
WO1998033528A9 WO1998033528A9 (en) 2001-06-14

Family

ID=25166795

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/002103 WO1998033528A2 (en) 1997-02-05 1998-02-05 Induction of b cell tolerance

Country Status (5)

Country Link
EP (1) EP0969872A2 (en)
JP (1) JP2001518074A (en)
AU (1) AU6319198A (en)
CA (1) CA2279544A1 (en)
WO (1) WO1998033528A2 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU761831B2 (en) * 1998-04-15 2003-06-12 Bioscience 2002 Llc Inhibition of xenoreactive antibodies
AU5132499A (en) * 1998-08-11 2000-03-06 Rush - Presbyterian - St. Luke's Medical Center Methods and compositions for preventing anti-gal production in xenograft recipients
US6458953B1 (en) 1998-12-09 2002-10-01 La Jolla Pharmaceutical Company Valency platform molecules comprising carbamate linkages
US6399578B1 (en) * 1998-12-09 2002-06-04 La Jolla Pharmaceutical Company Conjugates comprising galactose α1,3 galactosyl epitopes and methods of using same
WO2004028243A2 (en) 2002-08-21 2004-04-08 Revivicor, Inc. Porcine animals lacking any expression of functional alpha 1,3 galactosyltransferase
CA2548080A1 (en) 2003-11-05 2005-05-26 University Of Pittsburgh Porcine isogloboside 3 synthase protein, cdna, genomic organization, and regulatory region
JP2007529278A (en) 2004-03-17 2007-10-25 レビビコア， インコーポレイテッド Tissue products derived from animals lacking functional α1,3 galactosyltransferase
WO2015007326A1 (en) * 2013-07-18 2015-01-22 Institut D'investigació Biomèdica De Bellvitge (Idibell) Agents comprising a terminal alpha-galactosyl moiety for use in prevention and/or treatment of inflammatory diseases

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345732A2 (en) * 1988-06-09 1989-12-13 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Method to determine an antibody titre
WO1995020661A1 (en) * 1994-01-27 1995-08-03 Bresatec Ltd. Materials and methods for management of hyperacute rejection in human xenotransplantation
WO1997023637A1 (en) * 1995-12-21 1997-07-03 Procur Ab Galactopyranosides and their use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0345732A2 (en) * 1988-06-09 1989-12-13 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Method to determine an antibody titre
WO1995020661A1 (en) * 1994-01-27 1995-08-03 Bresatec Ltd. Materials and methods for management of hyperacute rejection in human xenotransplantation
WO1997023637A1 (en) * 1995-12-21 1997-07-03 Procur Ab Galactopyranosides and their use

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
GALILI U ET AL: "CONTRIBUTION OF ANTI-GAL TO PRIMATE AND HUMAN IGG BINDING TO PORCINE ENDOTHELIAL CELLS", TRANSPLANTATION, vol. 60, no. 2, 27 July 1995 (1995-07-27), pages 210 - 213, XP000564882 *
GALILI U ET AL: "HUMAN NATURAL ANTI-ALPHA-GALACTOSYL IGG. THE SPECIFIC RECOGNITION ALPHA(1 - 3)-LINKED GALACTOSE RESIDUES", JOURNAL OF EXPERIMENTAL MEDICINE, vol. 162, no. 2, 1 August 1985 (1985-08-01), pages 573 - 582, XP000677217 *
GALILI U: "EVOLUTION AND PATHOPHYSIOLOGY OF THE HUMAN NATURAL ANTI-ALPHA- GALACTOSYL IGG (ANTI-GAL) ANTIBODY", SPRINGER SEMINAR IN IMMUNOPATHOLOGY, vol. 15, no. 2/03, 1993, pages 155 - 171, XP000677551 *
GALILI U: "INTERACTION OF THE NATURAL ANTI-GAL ANTIBODY WITH ALPHA- GALACTOSYL EPITOPES: A MAJOR OBSTACLE FOR XENOTRANSPLANTATION IN HUMANS", IMMUNOLOGY TODAY, vol. 14, no. 10, 1993, pages 480 - 482, XP000672917 *
HENION T R ET AL: "Synthesis of alpha-gal epitopes on influenza virus vaccines, by recombinant alpha1,3galactosyltransferase, enables the formation of immune complexes with the natural anti-Gal antibody", VACCINE, vol. 15, no. 11, August 1997 (1997-08-01), pages 1174-1182, XP004086586 *
NILSSON K G I: "Glycosidase-Catalysed Synthesis of Di- and Trisaccharide Derivatives Related to Antigens Involved in the Hyperacute Rejection of Xenotransplants", TETRAHEDRON LETTERS, vol. 38, no. 1, 6 January 1997 (1997-01-06), pages 133-136, XP004070445 *
RIEBEN R ET AL: "DETECTION, IMMUNOABSORPTION, AND INHIBITION OF CYTOTOXIC ACTIVITY OF ANTI-ALPHAGAL ANTIBODIES USING NEWLY DEVELOPED SUBSTANCES WITH SYNTHETIC GAL ALPHA1-3GAL DISACCHARIDE EPITOPES", XENOTRANSPLANTATION, vol. 2, 1995, pages 98 - 106, XP000654455 *
SANDRIN M S ET AL: "ANTI-PIG IGM ANTIBODIES IN HUMAN SERUM REACT PREDOMINANTLY WITH GAL( -1,3)GAL EPITOPES", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 90, no. 23, 1 December 1993 (1993-12-01), pages 11391 - 11395, XP000561954 *
SANDRIN M S ET AL: "GALALPHA(1,3)GAL, THE MAJOR XENOANTIGEN(S) RECOGNISED IN PIGS BY HUMAN NATURAL ANTIBODIES", IMMUNOLOGICAL REVIEWS, vol. 141, no. 1, 1994, pages 169 - 190, XP000601268 *

Also Published As

Publication number Publication date
JP2001518074A (en) 2001-10-09
AU6319198A (en) 1998-08-25
EP0969872A2 (en) 2000-01-12
WO1998033528A9 (en) 2001-06-14
CA2279544A1 (en) 1998-08-06
WO1998033528A2 (en) 1998-08-06

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