WO1990014844A3 - Sugars as cleavable linkers for the delivery and release of agents in native form - Google Patents

Sugars as cleavable linkers for the delivery and release of agents in native form Download PDF

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Publication number
WO1990014844A3
WO1990014844A3 PCT/US1990/003008 US9003008W WO9014844A3 WO 1990014844 A3 WO1990014844 A3 WO 1990014844A3 US 9003008 W US9003008 W US 9003008W WO 9014844 A3 WO9014844 A3 WO 9014844A3
Authority
WO
WIPO (PCT)
Prior art keywords
linker
provides
compound
release
native form
Prior art date
Application number
PCT/US1990/003008
Other languages
French (fr)
Other versions
WO1990014844A2 (en
Inventor
Ananthachari Srinivasan
Vivekananda M Vrudhula
Original Assignee
Neorx 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 Neorx Corp filed Critical Neorx Corp
Publication of WO1990014844A2 publication Critical patent/WO1990014844A2/en
Publication of WO1990014844A3 publication Critical patent/WO1990014844A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/12—Acyclic radicals, not substituted by cyclic structures attached to a nitrogen atom of the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/24—Condensed ring systems having three or more rings
    • C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Optics & Photonics (AREA)
  • Immunology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The present invention provides a cleavable conjugate whose linker contains a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. Another aspect of the invention provides a method for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linker described above and is released in native form by a variety of mild conditions. An additional aspect of the invention provides a method for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of a reagent structurally related to the linker described above.
PCT/US1990/003008 1989-06-06 1990-05-30 Sugars as cleavable linkers for the delivery and release of agents in native form WO1990014844A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US36235589A 1989-06-06 1989-06-06
US362,355 1989-06-06

Publications (2)

Publication Number Publication Date
WO1990014844A2 WO1990014844A2 (en) 1990-12-13
WO1990014844A3 true WO1990014844A3 (en) 1991-03-07

Family

ID=23425768

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1990/003008 WO1990014844A2 (en) 1989-06-06 1990-05-30 Sugars as cleavable linkers for the delivery and release of agents in native form

Country Status (1)

Country Link
WO (1) WO1990014844A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5505931A (en) * 1993-03-04 1996-04-09 The Dow Chemical Company Acid cleavable compounds, their preparation and use as bifunctional acid-labile crosslinking agents
TWI660741B (en) * 2015-11-03 2019-06-01 財團法人工業技術研究院 Antibody-drug conjugate (adc) and method for forming the same
KR20230149857A (en) 2016-07-07 2023-10-27 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 Antibody adjuvant conjugates
CA3130794A1 (en) 2019-03-15 2020-09-24 Bolt Biotherapeutics, Inc. Immunoconjugates targeting her2

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0149760A2 (en) * 1983-12-07 1985-07-31 Bayer Ag Substituted O-acyl glycosylamides, methods for their preparation and their use
US4542225A (en) * 1984-08-29 1985-09-17 Dana-Farber Cancer Institute, Inc. Acid-cleavable compound
WO1987003286A1 (en) * 1985-11-29 1987-06-04 The University Of Melbourne Ricin-antibody conjugates
EP0251304A2 (en) * 1986-07-03 1988-01-07 Takeda Chemical Industries, Ltd. Glycosyl derivatives and use thereof
US4758421A (en) * 1985-03-15 1988-07-19 The Board Of Trustees Of The Leland Stanford Junior University Bleomycin conjugates and method
EP0318948A2 (en) * 1987-12-02 1989-06-07 Neorx Corporation Cleavable immunoconjugates for the delivery and release of agents in native form
EP0336364A2 (en) * 1988-04-06 1989-10-11 Neorx Corporation Modified cellular substrates used as linkers for increased cell retention of diagnostic and therapeutic agents

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0149760A2 (en) * 1983-12-07 1985-07-31 Bayer Ag Substituted O-acyl glycosylamides, methods for their preparation and their use
US4542225A (en) * 1984-08-29 1985-09-17 Dana-Farber Cancer Institute, Inc. Acid-cleavable compound
US4758421A (en) * 1985-03-15 1988-07-19 The Board Of Trustees Of The Leland Stanford Junior University Bleomycin conjugates and method
WO1987003286A1 (en) * 1985-11-29 1987-06-04 The University Of Melbourne Ricin-antibody conjugates
EP0251304A2 (en) * 1986-07-03 1988-01-07 Takeda Chemical Industries, Ltd. Glycosyl derivatives and use thereof
EP0318948A2 (en) * 1987-12-02 1989-06-07 Neorx Corporation Cleavable immunoconjugates for the delivery and release of agents in native form
EP0336364A2 (en) * 1988-04-06 1989-10-11 Neorx Corporation Modified cellular substrates used as linkers for increased cell retention of diagnostic and therapeutic agents

Also Published As

Publication number Publication date
WO1990014844A2 (en) 1990-12-13

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