WO2005112919A8 - Self-immolative linkers and drug conjugates - Google Patents

Self-immolative linkers and drug conjugates

Info

Publication number
WO2005112919A8
WO2005112919A8 PCT/US2005/017804 US2005017804W WO2005112919A8 WO 2005112919 A8 WO2005112919 A8 WO 2005112919A8 US 2005017804 W US2005017804 W US 2005017804W WO 2005112919 A8 WO2005112919 A8 WO 2005112919A8
Authority
WO
WIPO (PCT)
Prior art keywords
self
drug
drug conjugates
immolative linkers
ligand
Prior art date
Application number
PCT/US2005/017804
Other languages
French (fr)
Other versions
WO2005112919A2 (en
WO2005112919A3 (en
Inventor
Sharon Boyd
Liang Chen
Sanjeev Gangwar
Vincent Guerlavais
Kilian Horgan
Zhi-Hong Li
Bilal Sufi
Original Assignee
Medarex Inc
Sharon Boyd
Liang Chen
Sanjeev Gangwar
Vincent Guerlavais
Kilian Horgan
Zhi-Hong Li
Bilal Sufi
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
Priority to NZ550934A priority Critical patent/NZ550934A/en
Priority to JP2007527486A priority patent/JP4806680B2/en
Priority to CA2564076A priority patent/CA2564076C/en
Priority to BRPI0510909-4A priority patent/BRPI0510909A2/en
Priority to MXPA06013413A priority patent/MXPA06013413A/en
Priority to AU2005244980A priority patent/AU2005244980B2/en
Priority to CN200580020164.XA priority patent/CN1997402B/en
Priority to EP05752277.3A priority patent/EP1747021B1/en
Application filed by Medarex Inc, Sharon Boyd, Liang Chen, Sanjeev Gangwar, Vincent Guerlavais, Kilian Horgan, Zhi-Hong Li, Bilal Sufi filed Critical Medarex Inc
Publication of WO2005112919A2 publication Critical patent/WO2005112919A2/en
Priority to IL179077A priority patent/IL179077A/en
Publication of WO2005112919A8 publication Critical patent/WO2005112919A8/en
Priority to KR1020067026578A priority patent/KR101079023B1/en
Priority to NO20065881A priority patent/NO20065881L/en
Publication of WO2005112919A3 publication Critical patent/WO2005112919A3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K47/54—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 compound
    • A61K47/555—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 compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
    • A61K47/556—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 compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells enzyme catalyzed therapeutic agent [ECTA]
    • 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
    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
    • C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
    • C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
    • C07D501/34—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by carboxylic acids containing hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala

Abstract

The present disclosure provides drug-ligand conjugates that are potent cytotoxins, wherein the drug is linked to the ligand through either a peptidyl, hydrazine or disulfide self-immolative linker. In a particular embodiment the cytotoxin is represented by duocarmycins and derivatives thereof. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.
PCT/US2005/017804 2004-05-19 2005-05-19 Self-immolative linkers and drug conjugates WO2005112919A2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CN200580020164.XA CN1997402B (en) 2004-05-19 2005-05-19 Cytotoxic compounds and conjugates
CA2564076A CA2564076C (en) 2004-05-19 2005-05-19 Chemical linkers and conjugates thereof
BRPI0510909-4A BRPI0510909A2 (en) 2004-05-19 2005-05-19 cytotoxic drug-binder binding compound, pharmaceutical formulation, method for killing a cell and method for retarding or stopping tumor growth
MXPA06013413A MXPA06013413A (en) 2004-05-19 2005-05-19 Chemical linkers and conjugates thereof.
AU2005244980A AU2005244980B2 (en) 2004-05-19 2005-05-19 Chemical linkers and conjugates thereof
NZ550934A NZ550934A (en) 2004-05-19 2005-05-19 Chemical linkers and conjugates thereof
EP05752277.3A EP1747021B1 (en) 2004-05-19 2005-05-19 Self-immolative linkers and drug conjugates
JP2007527486A JP4806680B2 (en) 2004-05-19 2005-05-19 Self-sacrificing linker and drug conjugate
IL179077A IL179077A (en) 2004-05-19 2006-11-06 Chemical linkers and conjugates thereof
KR1020067026578A KR101079023B1 (en) 2004-05-19 2006-12-16 Chemical linkers and conjugates thereof
NO20065881A NO20065881L (en) 2004-05-19 2006-12-18 Chemical bonds and conjugates thereof

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US57266704P 2004-05-19 2004-05-19
US60/572,667 2004-05-19
US66117405P 2005-03-09 2005-03-09
US60/661,174 2005-03-09
US66987105P 2005-04-08 2005-04-08
US60/669,871 2005-04-08

Publications (3)

Publication Number Publication Date
WO2005112919A2 WO2005112919A2 (en) 2005-12-01
WO2005112919A8 true WO2005112919A8 (en) 2006-12-07
WO2005112919A3 WO2005112919A3 (en) 2007-02-01

Family

ID=35428830

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/017804 WO2005112919A2 (en) 2004-05-19 2005-05-19 Self-immolative linkers and drug conjugates

Country Status (12)

Country Link
US (1) US7517903B2 (en)
EP (1) EP1747021B1 (en)
JP (1) JP4806680B2 (en)
KR (1) KR101079023B1 (en)
AU (1) AU2005244980B2 (en)
BR (1) BRPI0510909A2 (en)
CA (1) CA2564076C (en)
IL (1) IL179077A (en)
MX (1) MXPA06013413A (en)
NO (1) NO20065881L (en)
NZ (1) NZ550934A (en)
WO (1) WO2005112919A2 (en)

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US9138484B2 (en) 2007-06-25 2015-09-22 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US9187521B2 (en) 2007-10-25 2015-11-17 Endocyte, Inc. Tubulysins and processes for preparing
US9296822B2 (en) 2005-12-08 2016-03-29 E.R. Squibb & Sons, L.L.C. Human monoclonal antibodies to O8E
US9505747B2 (en) 2012-03-29 2016-11-29 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
US9550734B2 (en) 2004-07-23 2017-01-24 Endocyte, Inc. Bivalent linkers and conjugates thereof
US9555139B2 (en) 2007-03-14 2017-01-31 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins

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