The present invention concerns antibody-conjugates which are especially suitable for the targeting of nectin-4-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
The present invention concerns antibody-conjugates which are especially suitable for the targeting of nectin-4-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y (1)
The present invention concerns antibody-conjugates which are especially suitable for the targeting of nectin-4-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y (1)
Herein, AB is an antibody capable of targeting nectin-4-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention relates to an antibody comprising a GlcNAc-S(A)x substituent, wherein S(A)x is a sugar derivative comprising x functional groups A wherein A is independently selected from the group consisting of an azido group, a keto group and an alkynyl group and x is 1, 2, 3 or 4, wherein said GlcNAc-S(A)x substituent is bonded to the antibody via C1 of the N-acetylglucosamine of said GlcNAc-S(A)x substituent, and wherein said N-acetylglucosamine is optionally fucosylated.
The present invention relates to an antibody comprising a GlcNAc-S(A)x substituent, wherein S(A)x is a sugar derivative comprising x functional groups A wherein A is independently selected from the group consisting of an azido group, a keto group and an alkynyl group and x is 1, 2, 3 or 4, wherein said GlcNAc-S(A)x substituent is bonded to the antibody via C1 of the N-acetylglucosamine of said GlcNAc-S(A)x substituent, and wherein said N-acetylglucosamine is optionally fucosylated.
The invention also relates to an antibody-conjugate, in particular to an antibody-conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1).
The present invention relates to an antibody comprising a GlcNAc-S(A)x substituent, wherein S(A)x is a sugar derivative comprising x functional groups A wherein A is independently selected from the group consisting of an azido group, a keto group and an alkynyl group and x is 1, 2, 3 or 4, wherein said GlcNAc-S(A)x substituent is bonded to the antibody via C1 of the N-acetylglucosamine of said GlcNAc-S(A)x substituent, and wherein said N-acetylglucosamine is optionally fucosylated.
The invention also relates to an antibody-conjugate, in particular to an antibody-conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1).
The present invention relates to an antibody comprising a GlcNAc-S(A)x substituent, wherein S(A)x is a sugar derivative comprising x functional groups A wherein A is independently selected from the group consisting of an azido group, a keto group and an alkynyl group and x is 1, 2, 3 or 4, wherein said GlcNAc-S(A)x substituent is bonded to the antibody via C1 of the N-acetylglucosamine of said GlcNAc-S(A)x substituent, and wherein said N-acetylglucosamine is optionally fucosylated.
The invention also relates to an antibody-conjugate, in particular to an antibody-conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1).
The invention further relates to a process for the preparation of a modified antibody, to a process for the preparation of an antibody-conjugate, and to said antibody-conjugate for use as a medicament.
The present invention relates to an antibody comprising a GlcNAc-S(A)x substituent, wherein S(A)x is a sugar derivative comprising x functional groups A wherein A is independently selected from the group consisting of an azido group, a keto group and an alkynyl group and x is 1, 2, 3 or 4, wherein said GlcNAc-S(A)x substituent is bonded to the antibody via C1 of the N-acetylglucosamine of said GlcNAc-S(A)x substituent, and wherein said N-acetylglucosamine is optionally fucosylated.
The invention also relates to an antibody-conjugate, in particular to an antibody-conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1).
The invention further relates to a process for the preparation of a modified antibody, to a process for the preparation of an antibody-conjugate, and to said antibody-conjugate for use as a medicament.
In addition, the invention relates to a kit of parts comprising an azide-modified antibody and a linker-conjugate, wherein said linker-conjugate comprises a (hetero)cycloalkynyl group and one or more molecules of interest.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
3.
ANTIBODY-CONJUGATES FOR TARGETING OF TUMOURS EXPRESSING PTK7
The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y 1
The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y 1
Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns antibody-conjugates which are especially suitable for the targeting of Trop-2-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
The present invention concerns antibody-conjugates which are especially suitable for the targeting of Trop-2-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y (1)
The present invention concerns antibody-conjugates which are especially suitable for the targeting of Trop-2-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y (1)
Herein, AB is an antibody capable of targeting Trop-2-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is exatecan; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns antibody-conjugates which are especially suitable for the targeting of CEA-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
The present invention concerns antibody-conjugates which are especially suitable for the targeting of CEA-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y (1)
The present invention concerns antibody-conjugates which are especially suitable for the targeting of CEA-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):
AB-[(L6)b-{Z-L-D}x]y (1)
Herein, AB is an antibody capable of targeting CEA-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
6.
FUSED CYCLOOCTYNE COMPOUNDS AND THEIR USE IN METAL-FREE CLICK REACTIONS
The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
C07C 29/58 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 67/347 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 271/12 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
C07C 271/20 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention is based on the surprising finding that the linker employed in a bioconjugate, such as an anti-body-drug conjugate, is not therapeutically inert but has an effect on the therapeutic index of the bioconjugate. The present invention thus concerns a method for increasing the therapeutic index of a bioconjugate and the bioconjugates for use in treatment, in particular cancer. The bioconjugates according to the invention have a sulfamide linker comprising a group according to formula (1):
The present invention is based on the surprising finding that the linker employed in a bioconjugate, such as an anti-body-drug conjugate, is not therapeutically inert but has an effect on the therapeutic index of the bioconjugate. The present invention thus concerns a method for increasing the therapeutic index of a bioconjugate and the bioconjugates for use in treatment, in particular cancer. The bioconjugates according to the invention have a sulfamide linker comprising a group according to formula (1):
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/66 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
xx containing x reactive moieties F, wherein x is an integer in the range 1 – 10, and an immune cell-engaging polypeptide containing one or two reactive moieties Q, wherein the antibody is specific for a tumour cell and the immune cell-engaging polypeptide is specific for an immune cell, wherein the reaction forms a covalent linkage between the functionalized antibody and the immune cell-engaging polypeptide by reaction of Q with F. The invention further concerns the antibody-cytokine conjugate obtainable by the process according to the invention and medical uses thereof.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention concerns nitrones that are capable of forming 4-isoxazoline compounds by strain- promoted alkyne-nitrone cycloaddition (SPANC), which have improved stability. The 4-isoxazoline compounds do not disintegrate by rearrangement into two molecules. As such, the nitrones according to the present invention are suitable for preparing bioconjugates by SPANC reaction. The invention further concerns the thus obtained bioconjugates, as well as the application thereof in targeting cells and treating cancer.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61P 37/00 - Drugs for immunological or allergic disorders
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
01 - Chemical and biological materials for industrial, scientific and agricultural use
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds for industrial and
scientific use. Chemical analysis, research and/or enzymatic modification of
proteins. Medical analysis for the diagnosis and treatment of a
condition in patients.
11.
HOMOGENEOUS ANTIBODY-CONJUGATES WITH HIGH PAYLOAD LOADING
The invention concerns homogenous antibody-conjugates with high payload loading (high DAR) obtained by site-specific conjugation to a single antibody N-glycan. The conjugates according to the invention are homogeneous, i.e. have a DAR at or close to the theoretical DAR with a narrow distribution, and do not require any genetic modification of the antibody. The invention further concerns a modular, non-genetic preparation method for such conjugates, involving three simple steps and starting from any antibody. These steps are (a) enzymatic remodeling of the glycan to give an antibody functionalized with two or four click probes per antibody, (b) strain-promoted cycloaddition with a multivalent, bifunctional reagent comprising one cyclic alkyne and at least two click probes that are not reactive towards the cyclic alkyne, and (c) inverse electron-demand Diels- Alder cycloaddition of the click probes with branched linker-drug constructs comprising one cyclic alkyne or strained alkene, connected to one or more payloads preferably connected through a cleavable linker. The resulting conjugates, with DAR6 or higher, are rapidly generated with high homogeneity and with surprising stability. In addition, HIC profiles of the resulting ADCs indicate small relative retention time and therefore show high potential in the targeting of tumour cells and/or the treatment of cancer.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 inventions concerns conjugates of masked PBD dimers, which are suitable in the treatment of cancers. The inventors found that coupling a masked PBD dimer via a glycan of a cell-binding agent increases the efficiency and tolerability of a PBD-payload. These findings allow for more effective cancer treatment with less adverse side-effects. The invention therefore concerns a conjugate of structure (1): wherein AB is a cell-binding agent; x is 1 or 2; y is 1 or 2; D is a masked PBD dimer payload; and L is a linker that connects AB with D.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07C 69/753 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of polycyclic acids
C07C 67/03 - Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
C07C 67/58 - SeparationPurificationStabilisationUse of additives by liquid-liquid treatment
C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 29/56 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by isomerisation
C07C 29/58 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
01 - Chemical and biological materials for industrial, scientific and agricultural use
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds being cells for industrial and scientific use Chemical analysis, research and chemical enzymatic modification of proteins for scientific research purposes Medical analysis for the diagnosis and treatment of cancer in patients
01 - Chemical and biological materials for industrial, scientific and agricultural use
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds for industrial and scientific use. Chemical and/or enzymatic modification of proteins in the development of antibody-drug conjugates; chemical and enzymatic modification of proteins (chemical engineering and biological development services). Medical analysis for the diagnosis and treatment of a condition in patients.
The invention concerns analogues of nemorubicin as well as PNU-159,682 with a range of substituents other than 2"-0Me on the morpholino ring that beneficially affected the toxicity of the toxin over the molecules with the 2"-0Me group. In addition, it was found that PNU variants with modified 2"-O-alkyl chain show enhanced tolerability in vivo. Thus, by modification of the 2"-O-alkyl group, ADCs were generated with carefully tailored potency and tolerability to improve the administered dose in patients. The invention thus concerns compounds according to structure (1) and conjugates therewith, as well as pharmaceutical compositions and methods of targeting tumour cells and treating cancer.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A process for preparing a glycoprotein-conjugate is provided, comprising: (a) providing an N-glycoprotein having an exposed tyrosine residue, wherein the exposed tyrosine residue is located within 10 amino acids of an N-glycosylation site, but the N-glycosylation site has been modified such that the glycoprotein does not contain a glycan longer than two monosaccharide residues within 10 amino acids of the exposed tyrosine residue; (b) converting the phenol moiety of the exposed tyrosine residue into an ortho-quinone moiety by contacting the glycoprotein with an oxidative enzyme capable of oxidizing tyrosine; and (c) reacting the ortho-quinone moiety with an alkene or alkyne compound via a [4+2] cycloaddition, wherein the compound comprises a (hetero)cycloalkene or (hetero)cycloalkyne moiety and (i) a chemical handle to further modify the compound with a payload, or (ii) a payload. The resulting glycoprotein-conjugates and pharmaceutical compositions and methods of treatment comprising same are also disclosed.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
18.
VIA CYCLOADDITION BILATERALLY FUNCTIONALIZED ANTIBODIES
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate having structure (1): wherein:
a, b and c are each independently 0 or 1;
L1, L2 and L3 are linkers;
D is a payload;
BM is a branching moiety;
Z are connecting groups obtainable by a cycloaddition reaction.
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate having structure (1): wherein:
a, b and c are each independently 0 or 1;
L1, L2 and L3 are linkers;
D is a payload;
BM is a branching moiety;
Z are connecting groups obtainable by a cycloaddition reaction.
The invention further provides a method for preparing the antibody-payload conjugate according to the invention, an intermediate compound in that preparation method, and medical uses of the antibody-payload conjugate according to the invention.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
The present invention provides antibody-conjugates which are conjugated via the glycan and still bind to a cell comprising an Fc-gamma receptor. The antibody conjugates according to the invention have structure (1):
The present invention provides antibody-conjugates which are conjugated via the glycan and still bind to a cell comprising an Fc-gamma receptor. The antibody conjugates according to the invention have structure (1):
Ab-[(GlcNAc(Fuc)b-(G)e-(Su-(Z-L-(D)r)x)s]y (1)
The present invention provides antibody-conjugates which are conjugated via the glycan and still bind to a cell comprising an Fc-gamma receptor. The antibody conjugates according to the invention have structure (1):
Ab-[(GlcNAc(Fuc)b-(G)e-(Su-(Z-L-(D)r)x)s]y (1)
Herein, Ab is an antibody; GlcNAc is an N-acetylglucosamine moiety; Fuc is a fucose moiety; b is 0 or 1; G is a monosaccharide; e is an integer in the range of 4-10; Su is a monosaccharide; Z is a connecting group obtained by a cycloaddition or a nucleophilic reaction; L is a linker; D is a payload; s is 1 or 2; r is an integer in the range of 1-4; x is 1 or 2; y is 2 or 4.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 invention relates to compounds of general structure (1): Q-(L1)n-(L2)o-(L3)p-(L4)q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3 and L4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21):
The invention relates to compounds of general structure (1): Q-(L1)n-(L2)o-(L3)p-(L4)q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3 and L4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21):
The invention relates to compounds of general structure (1): Q-(L1)n-(L2)o-(L3)p-(L4)q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3 and L4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21):
wherein R12═C1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L4)q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L6)-Z-(L1)n-(L2)o-(L3)p-(L4)q-D]xx (2), wherein Z is a connecting group that is formed in a click reaction, L6 is a linker that links Z to Pr and Pr is a (glyco)protein.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
21.
METHODS FOR THE PREPARATION OF LINKER PAYLOAD CONSTRUCTS
The present invention concerns a method for the preparation of an alkyne-linker-payload construct of structure Q-L-C(O)—NR3-D (1), comprising reacting (i) an alkyne compound of structure Q-L-C(O)-X (2), wherein Q is an alkyne moiety selected from the group consisting of terminal alkyne and (hetero)cycloalkyne; L is a linker, and X is a leaving group selected from halogen, SR1, O-succinimidyl, O-(hetero)aryl(R2)1-5, wherein R1 is selected from C1-C6 alkyl and (hetero)aryl; and R2 is C1-C6 alkyl, halogen or NO2; with (ii) a molecule of structure D-NHR3 (3), wherein D is a payload, and R3 is selected from hydrogen, optionally substituted C1-C24 alkyl, optionally substituted aryl. The activated ester derivatives (2) are highly stable and provide for smooth and high-yielding attachment to a cytotoxic payload. The invention further concerns a method for preparing bioconjugates and alkyne compound of structure Q-L-C(O)-X (2).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
The present invention concerns an antibody-drug conjugate, having structure (1)
The present invention concerns an antibody-drug conjugate, having structure (1)
The present invention concerns an antibody-drug conjugate, having structure (1)
wherein AB is an antibody; L1 and L2 are linkers; w is 0 or 1; Z is a connecting group obtained by a metal-free click reaction or by thiol ligation; each R17 is individually an amino acid side chain; n is an integer in the range of 1-5; A is a 5- or 6-membered aromatic or heteroaromatic ring; x is an integer in the range of 1-8; R21 is selected from H, R22, C(O)OH and C(O)R22, wherein R22 is C1-C24 (hetero)alkyl groups, C3-C10 (hetero)cycloalkyl groups, C2-C10 (hetero)aryl groups, C3-C10 alkyl(hetero)aryl groups and C3-C10 (hetero)arylalkyl groups, which optionally substituted and optionally interrupted by one or more heteroatoms selected from O, S and NR23 wherein R23 is independently selected from the group consisting of hydrogen and C1-C4 alkyl groups.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
24.
ANTIBODY-CONJUGATES FOR TARGETING OF TUMOURS EXPRESSING PTK7
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
25.
ANTIBODY-CONJUGATES FOR TARGETING OF TUMOURS EXPRESSING CARCINOEMBYRONIC ANTIGEN
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
26.
ANTIBODY-CONJUGATES FOR TARGETING OF TUMOURS EXPRESSING PTK7
6bxyy (1) Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6ww-(G)j-S-(L7w'w'-, wherein G is a monosaccharide, j is an integer in the range of 0 – 10, S is a sugar or a sugar derivative, GlcNAc is N- acetylglucosamine and Fuc is fucose, w is 0 or 1, w' is 0, 1 or 2 and L7is _2222-; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody- conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns antibody-conjugates which are especially suitable for the targeting of Trop-2-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1): Herein, AB is an antibody capable of targeting Trop-2-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6ww–(G)j–S–(L7ww'–, wherein G is a monosaccharide, j is an integer in the range of 0 – 10, S is a sugar or a sugar derivative, GlcNAc is N- acetylglucosamine and Fuc is fucose, w is 0 or 1, w' is 0, 1 or 2 and L72222–; D is exatecan; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns antibody-conjugates which are especially suitable for the targeting of CEA-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1): AB-[(L6bxyy (1) Herein, AB is an antibody capable of targeting CEA-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6wjj-S-(L7w2222-; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns antibody-conjugates which are especially suitable for the targeting of nectin-4-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1): AB–[(L6bxy y (1) Herein, AB is an antibody capable of targeting nectin-4-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6ww–(G)j–S–(L7w'w'–, wherein G is a monosaccharide, j is an integer in the range of 0 – 10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w' is 0, 1 or 2 and L72222–; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody- conjugates of structure (1) and application of the antibody-conjugates of structure (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A surfactant for a bioconjugation reaction is disclosed, wherein a biomolecule comprising one or more azide moieties is connected to an cyclic alkyne comprising payload. More specifically, the invention concerns a method for the preparation of a bioconjugate of structure B—(Z—L—D)x (1), comprising reacting (i) an alkyne or alkene compound of structure Q—L—D (2), wherein Q is a click probe comprising a cyclic alkyne moiety or a cyclic alkene moiety, L is a linker, and D is a payload; with (ii) a molecule of structure B—(F)x (3), wherein B is a biomolecule that is functionalized with x click probes F; F is a click probe capable of reacting with Q, and x is an integer in the range of 1-10, in presence of a surfactant.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns a process for preparing a multispecific antibody construct, comprising conjugating a functionalized antibody Ab(F)x containing x reactive moieties F, wherein x is an integer in the range 1 -10, and an immune cell-engaging polypeptide containing one or two reactive moieties Q, wherein the antibody is specific for a tumour cell and the immune cell-engaging polypeptide is specific for an immune cell, wherein the reaction forms a covalent linkage between the functionalized antibody and the immune cell-engaging polypeptide by reaction of Q with F. The invention further concerns the multispecific antibody constructs obtainable by the process according to the invention and medical uses thereof.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
32.
ANTIBODY-CONJUGATES WITH IMPROVED THERAPEUTIC INDEX FOR TARGETING HER2 TUMOURS AND METHOD FOR IMPROVING THERAPEUTIC INDEX OF ANTIBODY-CONJUGATES
The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F1)x—P in the presence of a catalyst, wherein S(F1)x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F1)x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q1 capable of reacting with functional group F1 and a target molecule D connected to Q1 via a linker L2 to obtain the antibody-conjugate wherein linker L comprises S—Z3-L2 and wherein Z3 is a connecting group resulting from the reaction between Q1 and F1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
33.
VIA CYCLOADDITION BILATERALLY FUNCTIONALIZED ANTIBODIES
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate is according to structure (1):
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate is according to structure (1):
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate is according to structure (1):
wherein:
a, b, c and d are each independently 0 or 1;
e is an integer in the range of 0-10;
L1, L2 and L3 are linkers;
D is a payload;
BM is a branching moiety;
Su is a monosaccharide;
G is a monosaccharide moiety;
GlcNAc is an N-acetylglucosamine moiety;
Fuc is a fucose moiety;
Z are connecting groups.
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate is according to structure (1):
wherein:
a, b, c and d are each independently 0 or 1;
e is an integer in the range of 0-10;
L1, L2 and L3 are linkers;
D is a payload;
BM is a branching moiety;
Su is a monosaccharide;
G is a monosaccharide moiety;
GlcNAc is an N-acetylglucosamine moiety;
Fuc is a fucose moiety;
Z are connecting groups.
The invention further provides a method for preparing the antibody-payload conjugate according to the invention, an intermediate compound in that preparation method, and medical uses of the antibody-payload conjugate according to the invention.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
34.
Process for the modification of a glycoprotein using a glycosyltransferase that is or is derived from a β(1,4)-n-acetylgalactosaminyltransferase
The present invention relates to a process for the enzymatic modification of a glycoprotein. The process comprises the step of contacting a glycoprotein comprising a glycan comprising a terminal GlcNAc-moiety, in the presence of glycosyltransferase that is, or is derived from, a β-(1,4)-N-acetylgalactosaminyltransferase, with a non-natural sugar-derivative nucleotide. The non-natural sugar-derivative nucleotide is according to formula (3):
24 allenyl groups and amino groups. The invention further relates to a glycoprotein obtainable by the process according to the invention, to a bioconjugate that can be obtained by conjugating the glycoprotein with a linker-conjugate, and to β-(1,4)-N-acetylgalactosaminyltransferases that can be used in preparing the glycoprotein according to the invention.
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
C07C 29/58 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
C07C 67/347 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 271/12 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
C07C 271/20 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention concerns multifunctional antibody construct containing at least one antibody Ab and two distinct payloads D1and D2of structure (1) or (2). Wherein L1, L2, L3, L4and L5are linkers; x1 and x2 are each individually an integer in the range of 1 – 8, wherein x1 + x2 = 2 - 10; BM is a branching moiety; m and n are each independently 0 or 1; x3 is an integer in the range of 1 - 4; and D1and D2are two distinct payloads selected from the group consisting of polypeptides, small molecules, cytotoxins and oligonucleotides, wherein at least one of D1and D2 is a polypeptide. The multifunctional antibody construct according to invention are suitable for use in medicine, such as for use in the treatment of cancer, a viral infection, a bacterial infection, a neurological disease, an autoimmune disease, an eye disease, hypercholesterolemia and amyloidosis.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
berxsyNN-acetylglucosamine moiety; Fuc is a fucose moiety; b is 0 or 1; G is a monosaccharide; e is an integer in the range of 4 - 10; Su is a monosaccharide; Z is a connecting group obtained by a cycloaddition or a nucleophilic reaction; L is a linker; D is a payload; s is 1 or 2; r is an integer in the range of 1 - 4; x is 1 or 2; y is 2 or 4.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns the finding that that natural N-glycoprotein are not sensitive to oxidative enzymes like tyrosinase or (poly)phenol oxidase, however if the native N-glycan is modified such that the glycoprotein does not contain a glycan longer than two monosaccharide residues within 10 amino acids of a tyrosine residue, that tyrosine residue of the glycoprotein becomes exposed, and susceptible to oxidative enzymes, leading to the formation of ortho-quinone. By performing the enzymatic oxidation in the presence of a strained alkyne or alkene, the resulting ortho-quinone undergoes in situ [4+2] cycloaddition to form conjugates having structure (1a) or (1b): (1a); Pr–[Z1–L–(Q2xyy or (1b); Pr–[Z1xyNN-glycoprotein; - Z1comprises structure (Za) or (Zb): wherein the carbon labelled with * is directly connected to the peptide chain of the antibody at an amino acid located within 10 amino acids of an N-glycosylation site, which has been modified such that the glycoprotein does not contain a glycan longer than two monosaccharide residues within 10 amino acids of the amino acid residue, and both of the carbon atoms labelled with ** are connected to L, and the bond depicted as (I) is a single bond or a double bond; - L is a linker; - x is an integer in the range of 1 – 4; - y is an integer in the range of 1 – 4; - Q2 is a chemical handle that is reactive towards an appropriately functionalized payload; - D is a payload.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 current invention concerns methods for the synthesis of 6-azido-6-deoxy-2-N-acetyl-monosaccharide-nucleoside diphosphate, in particular 6-azido-6-deoxy-2-N-acetyl-D-galactosamine-nucleoside diphosphate or 6-azido-6-deoxy-2-N-acetyl-D-glucosamine-nucleoside diphosphate. The synthesis method according to the invention is characterized by being highly efficient and high yielding. Also part of the present invention are key intermediates of this process.
The current invention concerns compounds, such as antibody-conjugates, with an enhanced selectivity of payload release inside a tumour or in the tumour microenvironment versus payload release in circulation or in healthy cells. The enhanced selectivity is achieved by incorporation of a cleavable linker that requires two consecutive mechanisms for release of the payload. The compounds according to the invention have structure (1):
The current invention concerns compounds, such as antibody-conjugates, with an enhanced selectivity of payload release inside a tumour or in the tumour microenvironment versus payload release in circulation or in healthy cells. The enhanced selectivity is achieved by incorporation of a cleavable linker that requires two consecutive mechanisms for release of the payload. The compounds according to the invention have structure (1):
The current invention concerns compounds, such as antibody-conjugates, with an enhanced selectivity of payload release inside a tumour or in the tumour microenvironment versus payload release in circulation or in healthy cells. The enhanced selectivity is achieved by incorporation of a cleavable linker that requires two consecutive mechanisms for release of the payload. The compounds according to the invention have structure (1):
or a salt thereof, wherein AB is an antibody or a reactive moiety capable of reacting with a functional group on an antibody, L1 and L2 are linkers, moiety I contains an activating group and an aromatic ring, X is O or N and D is the payload. The invention further concerns application of these compounds in for example a method of targeting a cell and a method for enhancing the bystander effect of an amino-containing payload. The invention also concerns the payloads that may be released from the compounds according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 31/4995 - Pyrazines or piperazines forming part of bridged ring systems
The present invention concerns an antibody-drug conjugate, having structure (1) wherein AB is an antibody; L1and L2are linkers; w is 0 or 1; Z is a connecting group obtained by a metal-free click reaction or by thiol ligation; each R17is individually an amino acid side chain; n is an integer in the range of 1 - 5; A is a 5- or 6-membered aromatic or heteroaromatic ring; x is an integer in the range of 1 - 8; R21is selected from H, R22, C(0)0H and C(0)R22, wherein R2212431021031031010 (hetero)arylalkyl groups, which optionally substituted and optionally interrupted by one or more heteroatoms selected from O, S and NR23wherein R23144 alkyl groups.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07D 491/00 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or
xxx (3), wherein B is a biomolecule that is functionalized with x click probes F; F is a click probe capable of reacting with Q, and x is an integer in the range of 1 – 10, in presence of a surfactant. The use of the surfactant increases the conversion of the bioconjugation reaction; increases the yield of the bioconjugation reaction; reduces the amount of organic co-solvent in the solvent system wherein the bioconjugation reaction is performed; provides flexibility in the concentration of biomolecule during the bioconjugation reaction; reduces the excess of alkyne- or alkene-functionalized payload used during the bioconjugation reaction; reduces the extent of aggregate formation during the bioconjugation reaction and simplifies downstream processing of the bioconjugate.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
and wherein the (hetero)cycloalkyne is a (hetero)cyclooctyne or a (hetero)cyclononyne according to Formula (1). The invention also relates to the products obtainable by the process according to the invention.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 271/18 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
C07D 225/02 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
C07D 225/08 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with two six-membered rings
C07D 231/54 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
44.
METHODS FOR THE PREPARATION OF LINKER PAYLOAD CONSTRUCTS
The present invention concerns a method for the preparation of an alkyne-linker-payload construct of structure Q-L-C (O)-NR3-D (1), comprising reacting (i) an alkyne compound of structure Q-L- C(O)-X (2), wherein Q is an alkyne moiety selected from the group consisting of terminal alkyne and (hetero)cycloalkyne; L is a linker, and X is a leaving group selected from halogen, SR1, O-succinimidyl, O-(hetero)aryl(R21-51-5, wherein R1166 alkyl and (hetero)aryl; and R21622; with (ii) a molecule of structure D-NHR3(3), wherein D is a payload, and R312424 alkyl, optionally substituted aryl. The activated ester derivatives (2) are highly stable and provide for smooth and high-yielding attachment to a cytotoxic payload. The invention further concerns a method for preparing bioconjugates and alkyne compound of structure Q-L-C (O)-X (2).
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
45.
ANTIBODY-CONJUGATES FOR TARGETING OF TUMOURS EXPRESSING TROP-2
The present invention concerns antibody-conjugate having general structure (2):
The present invention concerns antibody-conjugate having general structure (2):
AB-[(L6)-{Z-(L1)n-(L2)o-(L3)p-(L4)q-D}xx]yy (2)
The present invention concerns antibody-conjugate having general structure (2):
AB-[(L6)-{Z-(L1)n-(L2)o-(L3)p-(L4)q-D}xx]yy (2)
wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 invention relates to a novel linker for use in bioconjugates such as antibody-drug-conjugates. The linker according to the invention is represented by formula:
2 are connecting groups.
The linker according to the invention is useful in the preparation of linker-conjugates and bioconjugates, and can be used for (a) improving conjugation efficiency in the preparation of the bioconjugate, (b) reducing aggregation during the preparation of the bioconjugate and/or of the bioconjugate, (c) increasing stability of the bioconjugate, and/or (d) increasing therapeutic index of the bioconjugate.
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
p-EndoY (1), wherein EndoX is an endoglycosidase, EndoY is an endoglycosidase distinct from EndoX, L is a linker and p is 0 or 1. Such fusion enzymes capable of trimming glycoproteins comprising at least two distinct glycoforms in a single step. The invention further concerns the use of the fusion enzyme according to the invention for trimming glycoproteins. In another aspect, the invention relates to the process of production of the fusion enzyme. In a further aspect, the inventions concerns a process for trimming glycoproteins, comprising trimming the glycoprotein with a fusion enzyme according to the invention, to obtain a trimmed glycoprotein.
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12N 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate having structure (1): Formula (1) wherein: - a, b and c are each independently 0 or 1; - L1, L2and L3 are linkers; - D is a payload; - BM is a branching moiety; - Z are connecting groups obtainable by a cycloaddition reaction. The invention further provides a method for preparing the antibody-payload conjugate according to the invention, an intermediate compound in that preparation method, and medical uses of the antibody-payload conjugate according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate is according to structure (1): formula (1), wherein: - a, b, c and d are each independently 0 or 1; - e is an integer in the range of 0 - 10; - L1, L2and L3NN-acetylglucosamine moiety; - Fuc is a fucose moiety; - Z are connecting groups. The invention further provides a method for preparing the antibody-payload conjugate according to the invention, an intermediate compound in that preparation method, and medical uses of the antibody-payload conjugate according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
xx containing x reactive moieties F, wherein x is an integer in the range 1 – 10, and an immune cell-engaging polypeptide containing one or two reactive moieties Q, wherein the antibody is specific for a tumour cell and the immune cell-engaging polypeptide is specific for an immune cell, wherein the reaction forms a covalent linkage between the functionalized antibody and the immune cell-engaging polypeptide by reaction of Q with F. The invention further concerns the multispecific antibody constructs obtainable by the process according to the invention and medical uses thereof.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
x substituent, and wherein said N-acetylglucosamine is optionally fucosylated.
b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1).
The invention further relates to a process for the preparation of a modified antibody, to a process for the preparation of an antibody-conjugate, and to said antibody-conjugate for use as a medicament.
In addition, the invention relates to a kit of parts comprising an azide-modified antibody and a linker-conjugate, wherein said linker-conjugate comprises a (hetero)cycloalkynyl group and one or more molecules of interest.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
A61K 39/00 - Medicinal preparations containing antigens or antibodies
52.
Sulfamide linker, conjugates thereof, and methods of preparation
1 present on a biomolecule and on the omega-end a target molecule, the compound further comprising a group according to formula (1) or a salt thereof:
1 of a biomolecule. The invention further relates to a bioconjugate obtainable by the process according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
NNNN-acetyl-D-glucosamine-nucleoside diphosphate. The synthesis method according to the invention is characterized by being highly efficient and high yielding. Also part of the present invention are key intermediates of this process.
C07H 5/04 - Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
C07H 9/00 - Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
C07H 9/06 - Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing nitrogen as ring hetero atoms
The current invention concerns compounds, such as antibody-conjugates, with an enhanced selectivity of payload release inside a tumour or in the tumour microenvironment versus payload release in circulation or in healthy cells. The enhanced selectivity is achieved by incorporation of a cleavable linker that requires two consecutive mechanisms for release of the payload. The compounds according to the invention have structure (1) or a salt thereof, wherein AB is an antibody or a reactive moiety capable of reacting with a functional group on an antibody, L1 and L2 are linkers, moiety I contains an activating group and an aromatic ring, X is O or N and D is the payload. The invention further concerns application of these compounds in for example a method of targeting a cell and a method for enhancing the bystander effect of an amino-containing payload. The invention also concerns the payloads that may be released from the compounds according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns antibody-conjugate having general structure (2): AB–[(L 6)–{Z–(L 1) n –(L 2) o –(L 3) p –(L 4) q –D} xx ] yy (2) wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/532 - Production of labelled immunochemicals
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
C07C 29/58 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 67/347 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
C07C 271/12 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 271/20 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention is based on the surprising finding that the linker employed in a bioconjugate, such as an anti-body-drug conjugate, is not therapeutically inert but has an effect on the therapeutic index of the bioconjugate. The present invention thus concerns a method for increasing the therapeutic index of a bioconjugate and the bioconjugates for use in treatment, in particular cancer. The bioconjugates according to the invention have a sulfamide linker comprising a group according to formula (1).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/66 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
58.
Antibody-conjugates with improved therapeutic index for targeting CD30 tumours and method for improving therapeutic index of antibody-conjugates
1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting CD30-expressing cells.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 39/00 - Medicinal preparations containing antigens or antibodies
59.
Antibody-conjugates with improved therapeutic index for targeting HER2 tumours and method for improving therapeutic index of antibody-conjugates
1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention relates to compounds of general structure (1 ): Q-(L1nn-(L2oo-(L3pp-(L4qq-D, wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3and L4are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n + o + p + q = 1, 2, 3 or 4, wherein D comprises a functional moiety (21), wherein R121-31-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L4qq by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L6)-Z-(L1nn-(L2oo-(L3pp-(L4qxxxx, wherein Z is a connecting group that is formed in a click reaction, L6is a linker that links Z to Pr and Pr is a (glyco)protein.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
p-EndoY (1), wherein EndoX is an endoglycosidase, EndoY is an endoglycosidase distinct from EndoX, L is a linker and p is 0 or 1. Such fusion enzymes capable of trimming glycoproteins comprising at least two distinct glycoforms in a single step. The invention further concerns the use of the fusion enzyme according to the invention for trimming glycoproteins. In another aspect, the invention relates to the process of production of the fusion enzyme. In a further aspect, the inventions concerns a process for trimming glycoproteins, comprising trimming the glycoprotein with a fusion enzyme according to the invention, to obtain a trimmed glycoprotein.
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12N 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
2 are connecting groups. The linker according to the invention is useful in the preparation of linker-conjugates and bioconjugates, and can be used for (a) improving conjugation efficiency in the preparation of the bioconjugate, (b) reducing aggregation during the preparation of the bioconjugate and/or of the bioconjugate, (c) increasing stability of the bioconjugate, and/or (d) increasing therapeutic index of the bioconjugate.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
63.
Process for the modification of a glycoprotein using a glycosyltransferase that is or is derived from a β(1,4)-n-acetylgalactosaminyltransferase
The present invention relates to a process for the enzymatic modification of a glycoprotein. The process comprises the step of contacting a glycoprotein comprising a glycan comprising a terminal GlcNAc-moiety, in the presence of glycosyltransferase that is, or is derived from, a β-(1,4)-N-acetylgalactosaminyltransferase, with a non-natural sugar-derivative nucleotide. The non-natural sugar-derivative nucleotide is according to formula (3):
24 allenyl groups and amino groups. The invention further relates to a glycoprotein obtainable by the process according to the invention, to a bioconjugate that can be obtained by conjugating the glycoprotein with a linker-conjugate, and to β-(1,4)-N-acetylgalactosaminyltransferases that can be used in preparing the glycoprotein according to the invention.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds, being peptides, proteins, glycans, nucleotides, lipids and any other organic compound that is synthesized by a living organism, for industrial and scientific use. Pharmaceuticals for the in vivo treatment of a disease in patients. Chemical and biological engineering of biological molecules, with a focus on chemical and enzymatic modification of proteins. Medical analysis for the diagnosis and treatment of a condition in patients in the nature of medical advisory services.
1 present on a biomolecule and on the omega-end a target molecule, the compound further comprising a group according to formula (1) or a salt thereof:
1 of a biomolecule. The invention further relates to a bioconjugate obtainable by the process according to the invention.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
67.
IMPROVED SULFAMIDE LINKERS FOR USE IN BIOCONJUGATES
The invention relates to a novel linker for use in bioconjugates such as antibody-drug-conjugates. The linker according to the invention is represented by formula: (I) wherein: - BM is a branching moiety; - E is a capping group; - SG is a sulfamide group; - b, c, d, e, g, i, k, I are independently 0 or 1; - f is an integer in the range of 1 to 10; - Sp1, Sp2, Sp3, Sp4, Sp5 and Sp6 are a spacer moieties; - Z1 and Z2 are connecting groups. The linker according to the invention is useful in the preparation of linker-conjugates and bioconjugates, and can be used for (a) improving conjugation efficiency in the preparation of the bioconjugate, (b) reducing aggregation during the preparation of the bioconjugate and/or of the bioconjugate, (c) increasing stability of the bioconjugate, and/or (d) increasing therapeutic index of the bioconjugate.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present invention is based on the surprising finding that the linker employed in a bioconjugate, such as an anti-body-drug conjugate, is not therapeutically inert but has an effect on the therapeutic index of the bioconjugate. The present invention thus concerns a method for increasing the therapeutic index of a bioconjugate and the bioconjugates for use in treatment, in particular cancer. The bioconjugates according to the invention have a sulfamide linker comprising a group according to formula (1).
A61K 47/66 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1 - 4 core N-acetylglucosamine moieties with a compound of the formula S(F1)x-P in the presence of a catalyst, wherein S(F1)x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F1)x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q1 capable of reacting with functional group F1 and a target molecule D connected to Q1 via a linker L2 to obtain the antibody-conjugate wherein linker L comprises S-Z3-L2 and wherein Z3 is a connecting group resulting from the reaction between Q1 and F1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 present invention concerns novel and improved antibody-conjugates for targeting CD30. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1 - 4 core N-acetylglucosamine moieties with a compound of the formula S(F1)x-P in the presence of a catalyst, wherein S(F1)x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F1)X moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q1 capable of reacting with functional group F1 and a target molecule D connected to Q1 via a linker L2 to obtain the antibody-conjugate wherein linker L comprises S-Z3-L2 and wherein Z3 is a connecting group resulting from the reaction between Q1 and F1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting CD30-expressing cells.
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 invention concerns fusion proteins, wherein two endoglycosidases are fused, possibly via a linker. The fusion enzymes according to the invention have structure (1): EndoX-(L)p-EndoY (1), wherein EndoX is an endoglycosidase, EndoY is an endoglycosidase distinct from EndoX, L is a linker and p is 0 or 1. Such fusion enzymes capable of trimming glycoproteins comprising at least two distinct glycoforms in a single step. The invention further concerns the use of the fusion enzyme according to the invention for trimming glycoproteins. In another aspect, the invention relates to the process of production of the fusion enzyme. In a further aspect, the inventions concerns a process for trimming glycoproteins, comprising trimming the glycoprotein with a fusion enzyme according to the invention, to obtain a trimmed glycoprotein.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
24 allenyl groups and amino groups. The invention further relates to a glycoprotein obtainable by the process according to the invention, to a bioconjugate that can be obtained by conjugating the glycoprotein with a linker-conjugate, and to β-(1,4)-N-acetylgalactosaminyltransferases that can be used in preparing the the glycoprotein according to the invention.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
74.
Sulfamide linker, conjugates thereof, and methods of preparation
1 present on a biomolecule and on the omega-end a target molecule, the compound further comprising a group according to formula (1) or a salt thereof:
1 of a biomolecule. The invention further relates to a bioconjugate obtainable by the process according to the invention.
A61K 31/175 - Amides, e.g. hydroxamic acids having the group N—C(O)—N or N—C(S)—N, e.g. urea, thiourea, carmustine having the group , N—C(O)—N=N— or , e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazonesThioanalogues thereof
C07K 1/04 - General processes for the preparation of peptides on carriers
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
75.
Process for the cycloaddition of a halogenated 1,3-dipole compound with a (hetero)cycloalkyne
The present invention relates to a cycloaddition process comprising the step of reacting a halogenated aliphatic 1,3-dipole compound with a (hetero)cycloalkyne according to Formula (1): Preferably, the (hetero)cycloalkyne according to Formula (1) is a (hetero)cyclooctyne. The invention also relates to the cycloaddition products obtainable by the process according to the invention. The invention further relates to halogenated aliphatic 1,3-dipole compounds, in particular to halogenated aliphatic 1,3-dipole compounds comprising N-acetylgalactosamine-UDP (GalNAc-UDP), and to halogenated 1,3-dipole compounds comprising (peracylated) N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), N-acetylmannosamine (ManNAc) and N-acetyl neuraminic acid (NeuNAc).
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07C 247/04 - Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being saturated
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07C 247/18 - Compounds containing azido groups with azido groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
C07C 247/12 - Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
C07H 1/00 - Processes for the preparation of sugar derivatives
C07H 13/12 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by acids having the group —X—C (=X)—X—, or halides thereof, in which X means nitrogen, oxygen, sulfur, selenium, or tellurium, e.g. carbonic acid, carbamic acid
C07D 225/02 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
C07H 13/00 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
C07D 225/08 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with two six-membered rings
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
76.
Process for the cycloaddition of a hetero(aryl) 1,3-dipole compound with a (hetero)cycloalkyne
A process is provided, comprising reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne, wherein the (hetero)aryl 1,3-dipole compound comprises a 1,3-dipole functional group bonded to a (hetero)aryl group, and wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound;
wherein:
and wherein the (hetero)cycloalkyne is a (hetero)cyclooctyne or a (hetero)cyclononyne according to Formula (1). The invention also relates to the products obtainable by the process according to the invention.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07D 225/08 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with two six-membered rings
C07D 225/02 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
C07D 231/54 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 271/18 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
77.
PROCESS FOR THE MODIFICATION OF A GLYCOPROTEIN USING A GLYCOSYLTRANSFERASE THAT IS OR IS DERIVED FROM A β(1,4)-N-ACETYLGALACTOSAMINYLTRANSFERASE
The present invention relates to a process for the enzymatic modification of a glycoprotein. The process comprises the step of contacting a glycoprotein comprising a glycan comprising a terminal GlcNAc-moiety, in the presence of glycosyltransferasethat is,or is derived from,a β-(1,4)-N-acetylgalactosaminyltransferase, with anon-natural sugar-derivative nucleotide. Thenon-natural sugar-derivative nucleotide is according to formula (3): wherein A is selected from the group consisting of -N3, -C(O)R3, -(CH2)iC≡C-R4, - SH, -SC(O)R8, -SC(0)OR8, -SC(S)OR8, -F, -CI, -Br -I, -OS(O)2R5, terminal C2 - C24 alkenyl groups, C3 - C5 cycloalkenyl groups, C4 - C8 alkadienyl groups, terminal C3 - C24 allenyl groups and amino groups. The invention further relates to a glycoprotein obtainable by the process according to the invention, to a bioconjugate that can be obtained by conjugating the glycoprotein with a linker-conjugate, and to β-(1,4)-Ν- acetylgalactosaminyltransferases that can be used in preparing the the glycoprotein according to the invention.
The invention relates to a glycoprotein comprising an optionally fucosylated glycan according to formula (105) or (106), wherein Su(A)x is a modified sugar moiety comprising one or more functional groups A. Functional group A is independently selected from the group consisting of a thiol group, a halogen, a sulfonyloxy group, a halogenated acetamido group, a mercaptoacetamido group and a sulfonated hydroxyacetamido group. The invention also relates to a glycoprotein-conjugate wherein a glycoprotein according to the invention is conjugated to a molecule of interest. Said molecule of interest may for example be an active substance. The invention further relates to a process for the preparation of a modified glycoprotein, and to a method for the preparation of a glycoprotein-conjugate. The invention particularly relates to modified antibodies, antibody-conjugates, antibody-drug conjugates and methods for the preparation thereof.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
79.
Modified glycoprotein, protein-conjugate and process for the preparation thereof
x is a sugar derivative comprising x functional groups A, wherein x is 1, 2, 3 or 4 and A is independently selected from the group consisting of an azido group, a keto group, an alkynyl group, a thiol group, a halogen, a sulfonyloxy group, a halogenated acetamido group, a mercaptoacetamido group and a sulfonylated hydroxyacetamido group.
Protein-conjugates having glycoproteins according to the invention conjugated to a molecule of interest (e.g., an active substance) are also disclosed. Examples include modified antibodies, antibody-conjugates, and antibody-drug conjugates (ADCs). Processes for the preparation of the modified glycoproteins according to the invention and methods for the preparation of a protein-conjugate according to the invention are mentioned.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12P 19/18 - Preparation of compounds containing saccharide radicals produced by the action of a glycosyl transferase, e.g. alpha-, beta- or gamma-cyclodextrins
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
A61K 31/702 - Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
A61K 39/00 - Medicinal preparations containing antigens or antibodies
80.
Fused cyclooctyne compounds and their use in metal-free click reactions
The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
C07C 271/10 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 271/20 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
C07C 29/58 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 269/04 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
C07C 67/347 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/532 - Production of labelled immunochemicals
C07C 271/12 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds, being peptides, proteins,
glycans, nucleotides, lipids and any other organic compound
that is synthesized by a living organism, for industrial and
scientific use. Pharmaceuticals for the in vivo treatment of a disease in
patients. Chemical and biological engineering of biological molecules,
with a focus on chemical and enzymatic modification of
proteins. Medical analysis for the diagnosis and treatment of a
condition in patients in the nature of medical advisory
services.
82.
SULFAMIDE LINKER, CONJUGATES THEREOF, AND METHODS OF PREPARATION
The present invention relates to a compound comprising an alpha-end and an omega-end, the compound comprising on the alpha-end a reactive group Qlcapable of reacting with a functional group F1present on a biomolecule and on the omega-end a target molecule, the compound further comprising a group according to formula (1) or a salt thereof: Said compound may also be referred to as a linker-conjugate. The invention also relates to a process for the preparation of a bioconjugate, the process comprising the step of reacting a reactive group Q1of a linker-conjugate according to the invention with a functional group F1of a biomolecule. The invention further relates to a bioconjugate obtainable by the process according to the invention. In a preferred embodiment, the invention concerns a process for the preparation of a bioconjugate via a cycloaddition, such as a (4+2)-cycloaddition (e.g. a Diels-Alder reaction) or a (3+2)-cycloaddition (e.g. a 1,3-dipolar cycloaddition).
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
83.
PROCESS FOR THE MODIFICATION OF A GLYCOPROTEIN USING A ΒETA-(1,4)-N-ACETYLGALACTOSAMINYLTRANSFERASE OR A MUTANT THEREOF
The present invention relates to a process for the modification of a glycoprotein, using a β-(1,4)-N-acetylgalactosaminyltransferase or a mutant thereof.The process comprisesthe step of contacting a glycoprotein comprising a glycan comprising a terminal GlcNAc-moiety, in the presence of a β-(1,4)-N-acetylgalactosaminyl- transferase or a mutant thereof, with anon-natural sugar-derivative nucleotide.The non-natural sugar-derivative nucleotideis according to formula (3), wherein A is selected from the group consisting of -N3; -C(0)R3; -C=C-R4; -SH; -SC(0)R8; -SC(V)OR8, wherein V is O or S; -X wherein X is selected from the group consisting of F, CI, Br and I; -OS(0)2R5; an optionally substituted C2 - C24 alkyl group; an optionally substituted terminal C2 - C24 alkenyl group; and an optionally substituted terminal C3 - C24 allenyl group.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
[ Reagents and bioactive compounds, namely, peptides, proteins, glycans, nucleotides, and lipids that are all organic compounds synthesized by a living organism, for industrial and scientific use ] [ Pharmaceutical preparations for the in vivo treatment of cancer, autoimmune and inflammatory diseases in patients ] Chemical and biological engineering of biological molecules, with a focus on chemical and enzymatic modification of proteins Medical analysis for the diagnosis and treatment of a condition in patients in the nature of medical advisory services
85.
Modified antibody, antibody-conjugate and process for the preparation thereof
x substituent, and wherein said N-acetylglucosamine is optionally fucosylated. Also disclosed is an antibody-conjugate, in particular to an antibody-conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1).
Also disclosed is a process for the preparation of a modified antibody, to a process for the preparation of an antibody-conjugate, and to said antibody-conjugate for use as a medicament.
A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/00 - Medicinal preparations containing antigens or antibodies
86.
Modified antibody, antibody-conjugate and process for the preparation thereof
x substituent, and wherein said N-acetylglucosamine is optionally fucosylated. The invention also relates to an antibody-conjugate, in particular to an antibody-conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N-acetylglucosamine is optionally fucosylated (b is 0 or 1). The invention further relates to a process for the preparation of a modified antibody, to a process for the preparation of an antibody-conjugate, and to said antibody-conjugate for use as a medicament. In addition, the invention relates to a kit of parts comprising an azide-modified antibody and a linker-conjugate, wherein said linker-conjugate comprises a (hetero)cycloalkynyl group and one or more molecules of interest.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 39/00 - Medicinal preparations containing antigens or antibodies
87.
PROCESS FOR THE ATTACHMENT OF A GALNAC MOIETY COMPRISING A (HETERO)ARYL GROUP TO A GLCNAC MOIETY, AND PRODUCT OBTAINED THEREBY
The present invention relates to a process for attaching an N-acetylgalactosamine- (hetero)arylmoiety to an N-acetylglucosaminemoiety, the process comprising the step of contacting the N-acetylgalactosamine-(hetero)arylmoiety with the N- acetylglucosaminemoiety in the presence of a mutant galactosyltransferase, wherein the N-acetylglucosaminemoiety is according to Formula (1)the N- acetylgalactosamine-(hetero)arylmoiety is according to Formula (2): In a particularly preferred embodiment of the process according to the invention, the N-acetylgalactosamine-(hetero)arylmoiety comprises a 1,3-dipole functional group, and the N-acetylglucosaminemoiety is a terminal GlcNAc moiety of a glycoprotein glycan. The invention further relates to a productobtainable by the process according to the invention, in particular to glycoproteins. Also, the invention relates to several compounds comprising an N-acetylgalactosamine-(hetero)arylmoiety.
C12P 19/18 - Preparation of compounds containing saccharide radicals produced by the action of a glycosyl transferase, e.g. alpha-, beta- or gamma-cyclodextrins
The present invention relates to a cycloaddition process comprising the step of reacting a halogenated aliphatic 1,3-dipole compound with a (hetero)cycloalkyne according to Formula (1): Preferably, the (hetero)cycloalkyne according to Formula (1) is a (hetero)cyclooctyne. The invention also relates to the cycloaddition products obtainable by the process according to the invention. The invention further relates to halogenated aliphatic 1,3- dipole compounds, in particular tohalogenated aliphatic 1,3-dipole compounds comprising N-acetylgalactosamine-UDP (GalNAc-UDP),and to halogenated 1,3- dipole compounds comprising (peracylated) N-acetylglucosamine(GlcNAc), N- acetylgalactosamine(GalNAc), N-acetylmannosamine(ManNAc)and N- acetylneuraminic acid(NeuNAc).
C07D 225/02 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
C07D 225/08 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with two six-membered rings
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
89.
PROCESS FOR THE CYCLOADDITION OF A HETERO(ARYL) 1,3-DIPOLE COMPOUND WITH A (HETERO)CYCLOALKYNE
The present invention relates to a process comprising the step of reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne, wherein: a (hetero)aryl 1,3-dipole compound is defined as a compound comprising a 1,3-dipole functional group, wherein the 1,3-dipole functional group is bonded to a (hetero)aryl group, and wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound; wherein: (i) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound comprises one or more substituents having a positive value for the para-Hammett substituent constant σp and/or the meta-Hammett substituent constant σm, and/or (ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group, wherein an electron-poor (hetero)aryl group is: (ii-a) a (hetero)aryl group wherein the (hetero)aromatic ring system is bearing a positive charge, and/or (ii-b) a (hetero)aryl group wherein the ratio {number of π-electrons present in the (hetero)aromatic ring system} : {number of protons present in the nuclei of the (hetero)aromatic ring system} is lower than 0.167 for a 6-membered ring, or lower than 0.200 for a 5-membered ring; and wherein the (hetero)cycloalkyne is a (hetero)cyclooctyne or a (hetero)cyclononyne according to Formula (1): The invention also relates to the products obtainable by the process according to the invention.
C07D 225/02 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
C07D 225/08 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with two six-membered rings
C07D 231/54 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds, being peptides, proteins, glycans, nucleotides, lipids and any other organic compound that is synthesized by a living organism, for industrial and scientific use. Pharmaceuticals for the in vivo treatment of a disease in patients. Chemical and biological engineering of biological molecules, with a focus on chemical and enzymatic modification of proteins. Medical analysis for the diagnosis and treatment of a condition in patients in the nature of medical advisory services.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds, being peptides, proteins,
glycans, nucleotides, lipids and any other organic compounds
that are synthesized by a living organism, for industrial
and scientific use. Pharmaceuticals for the in vivo treatment of a disease in
patients. Chemical and biological engineering of biological molecules,
with a focus on chemical and enzymatic modification of
proteins. Medical analysis for the diagnosis and treatment of a
condition in patients in the nature of medical advisory
services.
92.
Fused cyclooctyne compounds and their use in metal-free click reactions
The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
C07C 33/16 - Alcohols containing rings other than six-membered aromatic rings containing rings with more than six ring members
C07C 271/10 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 271/20 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
C07C 29/58 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
C07C 269/04 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
C07C 67/347 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
G01N 33/532 - Production of labelled immunochemicals
C07C 271/12 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
93.
MODIFIED GLYCOPROTEIN, PROTEIN-CONJUGATE AND PROCESS FOR THE PREPARATION THEREOF
The invention relates to a glycoprotein comprising an optionally fucosylated glycan according to formula (105) or (106), wherein Su(A)x is a modified sugar moiety comprising one or more functional groups A. Functional group A is independently selected from the group consisting of a thiol group, a halogen, a sulfonyloxy group, a halogenated acetamido group, a mercaptoacetamido group and a sulfonated hydroxyacetamido group. The invention also relates to a glycoprotein-conjugate wherein a glycoprotein according to the invention is conjugated to a molecule of interest. Said molecule of interest may for example be an active substance. The invention further relates to a process for the preparation of a modified glycoprotein, and to a method for the preparation of a glycoprotein-conjugate. The invention particularly relates to modified antibodies, antibody-conjugates, antibody-drug conjugates and methods for the preparation thereof.
The present invention relates to a glycoprotein comprising a glycan of the formula (102), wherein b is 0 or 1, wherein the core GlcNAcresidue of said glycan is optionally fucosylated, wherein Su(A)x is a sugar derivative comprising x functional groups A wherein x is 1, 2, 3 or 4 and A is independently selected from the group consisting of an azido group, a keto group, an alkynyl group, a thiol group, a halogen, a sulfonyloxy group, a halogenated acetamido group, a mercaptoacetamido group and a sulfonylated hydroxyacetamido group. (Formula (102)), The invention further relates to a protein-conjugate wherein a modified glycoprotein according to the invention is conjugated to a molecule of interest. Said molecule of interest may for example be an active substance. The invention further relates to a process for the preparation of a modified glycoprotein according to the invention, and to a method for the preparation of a protein-conjugate according to the invention. The invention particularly relates to modified antibodies, antibody-conjugates, antibody-drug conjugates (ADCs) and methods for the preparation thereof.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
95.
GLYCOENGINEERED ANTIBODY, ANTIBODY-CONJUGATE AND METHODS FOR THEIR PREPARATION
The invention relates to glycoengineered antibodies and antibody-conjugates. In particular, the invention relates to an antibody conjugate, prepared from an IgG antibody comprising one N-linked glycosylation site on the combination of a single heavy chain and single light chain, wherein the N-linked glycosylation site is a mutant N-linked glycosylation site as compared to its wild type counterpart. The invention further relates to methods for the preparation of the antibody-conjugates according to the invention.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
The invention relates to glycoengineered antibodies and antibody-conjugates. In particular, the invention relates to an antibody conjugate, prepared from IgG antibody comprising at least two N-linked glycosylation sites on the combination of a single heavy chain and single light chain. The invention further relates to methods for the preparation of the antibody- conjugates according to the invention.In particular, the invention relates to an antibody-drug conjugate that is conjugated to different toxins, and the a process for the preparation thereof.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 1/107 - General processes for the preparation of peptides by chemical modification of precursor peptides
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
[ Reagents and bioactive compounds, being peptides, proteins, glycans, nucleotides, lipids and chemicals that are organic compounds synthesized by a living organism, for industrial and scientific use ] [ Pharmaceuticals for the in vivo treatment of cancer, autoimmune and inflammatory diseases in patients ] Chemical and biological engineering of biological molecules, with a focus on chemical and enzymatic modification of proteins Medical analysis for the diagnosis and treatment of a condition in patients in the nature of medical advisory services
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds, being peptides, proteins, glycans, nucleotides, lipids and any other organic compound that is synthesized by a living organism, for industrial and scientific use. Pharmaceuticals for the in vivo treatment of a disease in patients. Chemical and biological engineering of biological molecules, with a focus on chemical and enzymatic modification of proteins. Medical analysis for the diagnosis and treatment of a condition in patients in the nature of medical advisory services.
99.
SUBSTITUTED AZADIBENZOCYCLOOCTYNE COMPOUNDS AND THEIR USE IN METAL-FREE CLICK REACTIONS
The invention relates to a substituted azadibenzocyclooctyne compound according to Formula (5): The invention also relates to a conjugate wherein a substituted azadibenzocyclooctyne according to the invention is conjugated to a label, and to the use of these conjugates for bioorthogonal labeling, imaging or modification of a target molecule, e.g. surface modification. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.
C07D 225/08 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with two six-membered rings
01 - Chemical and biological materials for industrial, scientific and agricultural use
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Reagents and bioactive compounds for industrial and
scientific use. Chemical and/or enzymatic modification of proteins. Medical analysis for the diagnosis and treatment of a
condition in patients.
