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1. WO2020140123 - NOVEL METHIONINE CONTAINING ANTIBODIES FOR CONJUGATION OF AGENTS

Publication Number WO/2020/140123
Publication Date 02.07.2020
International Application No. PCT/US2019/068985
International Filing Date 30.12.2019
IPC
C07K 16/00 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/32 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
32against translation products from oncogenes
A61K 47/68 2017.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/00 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
CPC
A61K 47/6803
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
A61K 47/6849
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
6835the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
6849the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
A61K 47/6851
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
6835the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
6851the antibody targeting a determinant of a tumour cell
A61K 47/6889
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
6889Conjugates 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
C07K 16/32
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
32against translation products of oncogenes
C07K 2317/24
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2317Immunoglobulins specific features
20characterized by taxonomic origin
24containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
Applicants
  • THE REGENTS OF THE UNIVERSITY OF CALIFORNIA [US]/[US]
  • WELLS, James [US]/[US]
Inventors
  • WELLS, James
  • TRAN, Hai
  • ELLEDGE, Susanna
Agents
  • BERMAN, Matthew
Priority Data
62/786,33128.12.2018US
62/891,24923.08.2019US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) NOVEL METHIONINE CONTAINING ANTIBODIES FOR CONJUGATION OF AGENTS
(FR) NOUVEAUX ANTICORPS CONTENANT DE LA MÉTHIONINE POUR LA CONJUGAISON D'AGENTS
Abstract
(EN)
Provided herein are novel antibody-agent conjugates formed by the introduction of methionine residues to antibody scaffold light or heavy chains at select positions, followed by conjugation of the agent to the methionine, for example, by oxaziridine chemistries. Methionine substitutions at the targeted positions enable highly efficient functionalization to form very stable conjugates, including conjugates suitable for in vivo use. The positions were identified for the trastuzumab and other related scaffolds which can be engineered for affinity to any target antigen. The conjugates include ADCs and detections agents. Also disclosed are novel oxaziridine reagents for conjugation to methionines in proteins.
(FR)
La présente invention concerne de nouveaux conjugués anticorps-agent formés par l'introduction de résidus de méthionine dans des chaînes légères ou lourdes d'échafaudage d'anticorps à des positions sélectionnées, suivie par la conjugaison de l'agent avec la méthionine, par exemple, par des chimies d'oxaziridine. Des substitutions de méthionine aux positions ciblées permettent une fonctionnalisation hautement efficace en vue de former des conjugués très stables, notamment des conjugués appropriés pour une utilisation in vivo. Les positions ont été identifiées pour le trastuzumab et d'autres échafaudages apparentés qui peuvent être modifiés pour une affinité à un antigène cible quelconque. Les conjugués comprennent des ADC et des agents de détection. L'invention concerne également de nouveaux réactifs oxaziridine destinés à être conjugués à des méthionines dans des protéines.
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