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1. WO2021234471 - AN ANTIBODY FRAGMENT BASED ANTIMICROBIAL CONJUGATE SELECTIVELY TARGETING PSEUDOMONAS

Publication Number WO/2021/234471
Publication Date 25.11.2021
International Application No. PCT/IB2021/052989
International Filing Date 12.04.2021
IPC
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
CPC
A61K 47/6811
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
6811the drug being a protein or peptide, e.g. transferrin or bleomycin
A61K 47/6835
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
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 16/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
Applicants
  • ABGENICS LIFESCIENCES PRIVATE LIMITED [IN]/[IN]
Inventors
  • BANERJEE, Sanjiban Kumar
Agents
  • M., Madhavi
Priority Data
20202102076917.05.2020IN
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) AN ANTIBODY FRAGMENT BASED ANTIMICROBIAL CONJUGATE SELECTIVELY TARGETING PSEUDOMONAS
(FR) CONJUGUÉ ANTIMICROBIEN À BASE DE FRAGMENT D'ANTICORPS CIBLANT SÉLECTIVEMENT PSEUDOMONAS
Abstract
(EN) The present invention relates to a novel antibody fragment based antimicrobial conjugate selectively targeting Pseudomonas spp., preferably Pseudomonas aeruginosa, comprising of at least one antimicrobial peptide at one end of the conjugate preferably human Histatin-5; at least one antibody fragment at the other end of the conjugate, preferably a VHH targeting C4 decarboxylase transporterantigen of Pseudomonas aeruginosa; at least one protease cleavage sequence, preferably susceptible to cleavage by Pseudomonas aeruginosa specific virulent protease, Elastase B, and at least one flexible polypeptide linker in tandem with the protease cleavage sequence, and the protease cleavage sequence and the flexible polypeptide linker placedin between the antimicrobial peptide and antibody fragment. The antibody fragment based antimicrobial conjugatehas anin vitro MIC-99 against Pseudomonas aeruginosa of 0.5 µM, and MIC-50 less than 0.125 µM. Itcan be easily manipulated for generating next generation of conjugates in case of emergence of drug-resistant forms of the pathogen.
(FR) La présente invention concerne un nouveau conjugué antimicrobien à base de fragment d'anticorps ciblant sélectivement Pseudomonas spp., de préférence Pseudomonas aeruginosa, comprenant au moins un peptide antimicrobien à une extrémité du conjugué, de préférence l'histatine-5 humaine ; au moins un fragment d'anticorps à l'autre extrémité du conjugué, de préférence un VHH ciblant un antigène transporteur de C4 décarboxylase de Pseudomonas aeruginosa ; au moins une séquence de clivage de protéase, de préférence susceptible de clivage par une protéase virulente spécifique de Pseudomonas aeruginosa, une élastase B, et au moins un lieur polypeptidique flexible en tandem avec la séquence de clivage de protéase, et la séquence de clivage de protéase et le lieur polypeptidique flexible étant placés entre le peptide antimicrobien et le fragment d'anticorps. Le conjugué antimicrobien à base de fragment d'anticorps a un MIC-99 in vitro contre Pseudomonas aeruginosa de 0,5 µM, et un MIC-50 inférieur à 0,125 µM. Le conjugué antimicrobien peut être facilement manipulé pour générer la prochaine génération de conjugués en cas d'émergence de formes pharmacorésistantes de l'agent pathogène.
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