US2024000963A1PendingUtilityA1
Hydrophilic linkers and conjugates thereof
Est. expiryJun 21, 2037(~10.9 yrs left)· nominal 20-yr term from priority
A61P 35/00A61K 31/675A61K 31/704A61K 45/00A61K 47/6849A61K 47/6835A61K 47/59A61K 47/68031A61K 47/6803A61K 47/6855A61K 47/65A61K 47/549A61K 47/6809
75
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Claims
Abstract
Hydrophilic linkers and their conjugates are disclosed. Formula (I) (II)
Claims
exact text as granted — not AI-modified1 . A linker-payload conjugate of Formula I
wherein X is either absent or a spacer group; R 1 is an amino acid side chain; R 2 is H, an alkyl group, an aryl group, or a halide; Y is a hydrophilic group; R 3 is an amino acid side chain; Z is either absent or a self-immolative group; D is a payload molecule; and m is either 0 or 1.
2 . The linker-payload conjugate of claim 1 and according to Formula III
wherein X is a spacer group comprising a maleimide and D is a payload molecule, or according to any one of Formula IIIb, Formula IIIc and Formula IIId:
wherein X is a spacer group comprising a maleimide or an azide-reactive group and D is a payload molecule.
3 . A targeting unit-linker-payload conjugate of Formula II
wherein T is a targeting unit; X is either absent or a spacer group; R 1 is an amino acid side chain; R 2 is H, an alkyl group, an aryl group, or a halide; Y is a hydrophilic group; R 3 is an amino acid side chain; Z is either absent or a self-immolative group; D is a payload molecule; m is either 0 or 1; and n is an integer≥1.
4 . The targeting unit-linker-payload conjugate of claim 3 and according to Formula IV
wherein T is an antibody; n is between 1 and about 20; X is a spacer group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; and D is a payload molecule; or
according to any one of Formula IVb, Formula IVc and Formula IVd:
wherein T is an antibody; n is between 1 and about 20, or n is 6, 7, or 8, or n is 2 or 4; X is a spacer group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond, or X is a spacer group comprising a azide-reactive group connected to a azide group in the antibody via a 1,3-triazole; and D is a payload molecule.
5 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein Y is selected from the group consisting of a saccharide, phosphate ester, sulfate ester, a phosphodiester and a phosphonate.
6 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein the saccharide comprises or consists of β-D-galactose, N-acetyl-β-D-galactosamine, N-acetyl-α-D-galactosamine, N-acetyl-β-D-glucosamine, β-D-glucuronic acid, α-L-iduronic acid, α-D-galactose, α-D-glucose, β-D-glucose, α-D-mannose, β-D-mannose, α-L-fucose, α-D-xylose, a neuraminic acid or any analogue or modification thereof, or sulfate, phosphate, carboxyl, amino, or O-acetyl modification thereof.
7 . The linker-payload conjugate of claim 6 or the targeting unit-linker-payload conjugate of claim 6 , wherein the saccharide consists of β-D-glucose, N-acetyl-β-D-glucosamine, β-D-glucuronic acid or α-L-fucose.
8 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein the cleavable hydrophilic group Y is cleavable by an enzyme, for example, an intracellular enzyme, a lysosomal enzyme or a cytoplasmic enzyme.
9 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein payload molecule D is selected from the group consisting of a cytotoxic drug, an immunomodulatory agent, a labeling agent, a chelator and a radioactive agent.
10 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein D is a cytotoxic drug selected from the group consisting of dolastatins; auristatins; epothilones; daunorubicins and doxorubicins; alkylating agents, such as thiotepa and cyclophosphamide (CYTOXAN™); alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines, such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylene-phosphoramide, triethylenethiophosphaoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); camptothecins (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); duocarmycin (including the synthetic analogues, KW-2189 and CBI-TMI); eleutherobin; pancratistatin; sarcodictyins; spongistatin; nitrogen mustards such as chlorambucil, chlomaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, ranimustine; antibiotics, such as the enediyne antibiotics (e.g. calicheamicins, especially calicheamicin γ1; dynemicin, including dynemicin A; esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromomophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin; chromomycins, dactinomycin, detorubicin, 6-diazo-5-oxo-L-norleucine, other doxorubicin derivatives including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin, epirubicin, esorubicin, idarubicin, marcellomycin, nitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites, such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues, such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs, such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, 5-fluorouracil; androgens, such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals, such as aminoglutethimide, mitotane, trilostane; folic acid replenisher, such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfomithine; elliptinium acetate; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidamine; maytansinoids, such as maytansine and N-glucosylmaytansinoids, ansamitocins, DM-1, DM-4; mitoguazone; mitoxantrone; mopidamol; nitracrine; pentostatin; phenamet; pirarubicin; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK®; razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2′,2″-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g. paclitaxel (TAXOL®, Bristol-Myers Squibb Oncology, Princeton, N.J.) and doxetaxel (TAXOTERE®, Rhone-Poulenc Rorer, Antony, France); chlorambucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitomycin C; mitoxantrone; vincristine; vinorelbine; navelbine; novantrone; teniposide; daunomycin; aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylomithine (DMFO); retinoic acid; capecitabine; tamoxifen, raloxifene, aromatase inhibiting 4(5)-imidazoles, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and toremifene (Fareston); and anti-androgens, such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; tubulysins; amanitins, such as α-amanitin; and pharmaceutically acceptable salts, acids; dolastatin 10 or any derivative thereof; dolastatin 15 or any derivative thereof; auristatin F or any derivative thereof; monomethyl and desmethyl dolastatins 10, 15, C, D and H, monomethyl and desmethyl isodolastatin H, and analogues and derivatives thereof; monomethyl and desmethyl auristatins E, F, EB, EFP, PY, PYE, PE, PHE, TP, 2-AQ and 6-AQ; maytansinoids; N-glucosylmaytansinoid; maytansine, an ansamitocin, DM1 (also known as mertansine) or DM4 (also known as DM-4); daunorubicins, doxorubicins, detorubicin, other doxorubicin derivatives including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin, deoxydoxorubicin, epirubicin, esorubicin, idarubicin, rodorubicin, zorubicin, and pirarubicin; duocarmycin A, duocarmycin B1, duocarmycin B2, duocarmycin C1, duocarmycin C2, duocarmycin D, duocarmycin SA, duocarmycin MA, and CC-1065; synthetic analogs of duocarmycins, such as adozelesin, bizelesin, carzelesin, KW-2189 and CBI-TMI; duocarmycin-saccharide conjugate of Formula DS; tubulysin; α-amanitin; cryptophycin; monomethylauristatin E; an auristatin saccharide conjugate of Formula AS; MMAU; monomethylauristatin F, W or M; a pyrrolobenzodiazepine (PBD), abbeymycin, chicamycin, DC-81, mazethramycin, neothramycins A and B, porothramycin, prothracarcin, sibiromycin, tomamycin, and a PBD dimer; or an analogue of any of the above.
11 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein R 3 is selected from the group consisting of a side chain of α-amino acid, serine, threonine and tyrosine.
12 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein X is selected from the group consisting of acyl group, alkyl group, aryl group, an amino acid, and a bioorthogonal linking group.
13 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein the bioorthogonal linking group comprises azide, alkyne, triazole, maleimide, thiol, amine, carboxylic acid, amide, alkene, ether, thioether, aldehyde, ketone, hydroxylamine, hemiacetal, acetal, phosphine, tetrazine, cyclooctene, nitrone, isoxazoline, nitrile oxide, norbornene, oxanorbornadiene, tetrazole, pyrazoline and quadricyclane.
14 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein Z is selected from the group consisting of para-aminobenzyloxycarbonyl (PABC), orto-aminobenzyloxycarbonyl, an amino acid and a peptide.
15 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein R 1 is selected from the group consisting of side chain of a α-amino acid, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine.
16 . The linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim, wherein
Y is a saccharide and R 3 is a side chain of an amino acid; Y is β-D-glucose and R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; Y is β-D-glucose and R 3 is the side chain of serine; Y is a saccharide; R 3 is a side chain of an amino acid; and R 2 is H; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; and R 2 is H; Y is β-D-glucose; R 3 is the side chain of serine; and R 2 is H; Y is a saccharide; R 3 is a side chain of an amino acid; R 2 is H; m=1; and R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; and R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; and R 1 is the side chain of valine; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; and R 1 is the side chain of valine; Y is a saccharide; R 3 is a side chain of an amino acid; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; and Z is PABC; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; and Z is PABC; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; and Z is PABC; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; and Z is PABC; Y is a saccharide; R 3 is a side chain of an amino acid; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; and D is a cytotoxic drug; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; and D is a cytotoxic drug; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is a cytotoxic drug; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is a cytotoxic drug; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is a cytotoxic drug; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is a cytotoxic drug; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is a cytotoxic drug; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is an auristatin; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is an auristatin; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is an auristatin; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is MMAU; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is MMAU; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is MMAU; Y is a saccharide; R 3 is a side chain of an amino acid; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide; the linker-payload conjugate is according to Formula III, wherein D is a cytotoxic drug; the linker-payload conjugate is according to Formula III, wherein D is an auristatin; the linker-payload conjugate is according to Formula III, wherein D is MMAU; the linker-payload conjugate is maleimidocaproyl-Val-Ser(Glc)-PABC-MMAU according to Formula V
the linker-payload conjugate is according to Formula III, wherein D is a cytotoxic drug;
the linker-payload conjugate is according to Formula III, wherein D is an auristatin;
the linker-payload conjugate is according to Formula III, wherein D is MMAU;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; and D is a cytotoxic drug;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is a cytotoxic drug;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is a cytotoxic drug;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is a cytotoxic drug;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is an auristatin;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is a rubicin or a doxorubicin derivative;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; and D is a rubicin or a doxorubicin derivative;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is a rubicin or a doxorubicin derivative;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is a rubicin or a doxorubicin derivative;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is an auristatin;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is a rubicin or a doxorubicin derivative;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is a rubicin or a doxorubicin derivative;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is a rubicin or a doxorubicin derivative;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is a rubicin or a doxorubicin derivative;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is MMAU;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is PNU-EDA;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; and D is PNU-EDA;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; and D is PNU-EDA;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; and D is PNU-EDA;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is PNU-EDA;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; and D is PNU-EDA;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is MMAU;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is PNU-EDA;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; and D is PNU-EDA;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R z is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a rubicin or a doxorubicin derivative; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of an α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R z is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
T is an antibody; n is between 1 and about 20; Y is β-D-glucuronic acid; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is PNU-EDA; and X is an acyl group comprising an azide-reactive group connected to an azide group in the antibody via a 1,3-triazole;
the linker-payload conjugate comprises the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is a cytotoxic drug. In an embodiment, the linker-payload conjugate is the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is a cytotoxic drug;
the linker-payload conjugate comprises the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is an auristatin. In an embodiment, the linker-payload conjugate is the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is an auristatin;
the linker-payload conjugate comprises the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is MMAU. In an embodiment, the linker-payload conjugate is the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is MMAU;
the linker-payload conjugate comprises the linker-payload conjugate according to Formula III, Formula IIIb, Formula IIIc or Formula IIId, wherein D is a rubicin or a doxyrubicin derivative. In an embodiment, the linker-payload conjugate is the linker-payload conjugate according to Formula III, Formula IIIb, Formula IIIc or Formula IIId, wherein D is a rubicin or a doxyrubicin derivative;
the linker-payload conjugate comprises the linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is PNU-EDA;
the linker-payload conjugate is the linker-payload conjugate according to Formula III, Formula IIIb, Formula IIIc or Formula IIId, wherein D is PNU-EDA;
the linker-payload conjugate is DBCO-Val-Ser(GlcA)-PNU-EDA according to Formula Vb
the targeting unit-linker-payload conjugate comprises the targeting unit-linker-payload conjugate according to Formula IVb, Formula IVc or Formula IVd, wherein D is a cytotoxic drug. In an embodiment, the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IVb, Formula IVc or Formula IVd, wherein D is a cytotoxic drug;
the targeting unit-linker-payload conjugate comprises the targeting unit-linker-payload conjugate according to Formula IVb, wherein D is an auristatin. In an embodiment, the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IVb, wherein D is an auristatin;
the targeting unit-linker-payload conjugate comprises the targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is a rubicin or a doxorubicin derivative. In an embodiment, the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is a rubicin or a doxorubicin derivative;
the targeting unit-linker-payload conjugate comprises the targeting unit-linker-payload conjugate according to Formula IVb, wherein D is MMAU. In an embodiment, the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IVb, wherein D is MMAU;
the targeting unit-linker-payload conjugate comprises the targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is PNU-EDA. In an embodiment, the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is PNU-EDA;
the targeting unit-linker-payload conjugate is antibody-DBCO-Val-Ser(GlcA)-PNU-EDA according to Formula VIb
wherein T is an antibody connected from an azide group via a 1,3-triazole and n is between 1 and about 4;
the targeting unit-linker-payload conjugate comprises or is a targeting unit-linker-payload conjugate according to Formula IVb, Formula IVc or Formula IVd, wherein D is a cytotoxic drug and T is trastuzumab;
the targeting unit-linker-payload conjugate comprises or is a targeting unit-linker-payload conjugate according to Formula IVb, wherein D is MMAU and T is trastuzumab;
the targeting unit-linker-payload conjugate comprises or is a targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is PNU-EDA and T is trastuzumab;
the targeting unit-linker-payload conjugate comprises or is a conjugate selected from the group consisting of the following:
a targeting unit-linker-payload conjugate according to Formula IVb, Formula IVc or Formula IVd, wherein D is a cytotoxic drug;
a targeting unit-linker-payload conjugate according to Formula IVb, wherein D is an auristatin;
a targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is a rubicin or a doxorubicin derivative;
a targeting unit-linker-payload conjugate according to Formula IVb, wherein D is MMAU;
a targeting unit-linker-payload conjugate according to Formula IV, Formula IVb, Formula IVc or Formula IVd, wherein D is PNU-EDA; or
the conjugate comprises or is a conjugate selected from the group consisting of the following:
a linker-payload conjugate according to Formula IIIb, Formula IIIc or Formula IIId, wherein D is a cytotoxic drug;
a linker-payload conjugate according to Formula IIIb, wherein D is an auristatin;
a linker-payload conjugate according to Formula III, Formula IIIb, Formula IIIc or Formula IIId, wherein D is a rubicin or a doxorubicin derivative;
a linker-payload conjugate according to Formula IIIb, wherein D is MMAU;
a linker-payload conjugate according to Formula III, Formula IIIb, Formula IIIc or Formula IIId, wherein D is PNU-EDA.
17 . The targeting unit-linker-payload conjugate of any preceding claim, wherein the targeting unit is an antibody.
18 . The targeting unit-linker-payload conjugate of claim 17 , wherein the antibody is selected from the group consisting of bevacizumab, tositumomab, etanercept, trastuzumab, adalimumab, alemtuzumab, gemtuzumab ozogamicin, efalizumab, rituximab, infliximab, abciximab, basiliximab, palivizumab, omalizumab, daclizumab, cetuximab, panitumumab, epratuzumab, 2G12, lintuzumab, nimotuzumab and ibritumomab tiuxetan, or the antibody is selected from the group consisting of an anti-EGFR1 antibody, an epidermal growth factor receptor 2 (HER2/neu) antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-Lewis y antibody and an anti-CD20 antibody.
19 . The targeting unit-linker-payload conjugate of any preceding claim, wherein n is in the range of 1 to about 20, or 1 to about 15, or 1 to about 10, or 2 to 10, or 2 to 6, or 2 to 5, or 2 to 4; 3 to about 20, or 3 to about 15, or 3 to about 10, or 3 to about 9, or 3 to about 8, or 3 to about 7, or 3 to about 6, or 3 to 5, or 3 to 4; 4 to about 20, or 4 to about 15, or 4 to about 10, or 4 to about 9, or 4 to about 8, or 4 to about 7, or 4 to about 6, or 4 to 5; or about 7-9; or about 8; or n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.
20 . The targeting unit-linker-payload conjugate of any preceding claim, wherein
T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is a side chain of an amino acid; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is absent; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is a cytotoxic drug; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is an auristatin; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of a α-amino acid, serine, threonine or tyrosine; R 2 is H; m=1; R 1 is selected from the group of side chains of α-amino acids, valine, phenylalanine, tyrosine, leusine, isoleusine, arginine, alanine, lysine and glycine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is a saccharide; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; T is an antibody; n is between 1 and about 20; Y is β-D-glucose; R 3 is the side chain of serine; R 2 is H; m=1; R 1 is the side chain of valine; Z is PABC; D is MMAU; and X is an acyl group comprising a maleimide connected to a cysteine side chain of the antibody via a thioether bond; the targeting unit-linker-payload conjugate is according to Formula IV, wherein D is a cytotoxic drug; the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IV, wherein D is an auristatin; the targeting unit-linker-payload conjugate is the targeting unit-linker-payload conjugate according to Formula IV, wherein D is MMAU; the targeting unit-linker-payload conjugate is antibody-maleimidocaproyl-Val-Ser(Glc)-PABC-MMAU according to Formula VI
wherein T is an antibody connected from a cysteine side chain via a thioether bond and n is between 1 and about 20;
the targeting unit-linker-payload conjugate is according to Formula IV, wherein D is a cytotoxic drug and T is trastuzumab;
the targeting unit-linker-payload conjugate is according to Formula IV, wherein D is MMAU and T is trastuzumab;
the targeting unit-linker-payload conjugate is according to Formula IV, wherein D is a cytotoxic drug;
the targeting unit-linker-payload conjugate is according to Formula IV, wherein D is an auristatin;
the targeting unit-linker-payload conjugate is according to Formula IV, wherein D is MMAU;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is an antibody connected from a cysteine side chain via a thioether bond and n is 5;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is an antibody connected from a cysteine side chain via a thioether bond and n is 6;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is an antibody connected from a cysteine side chain via a thioether bond and n is 7;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is an antibody connected from a cysteine side chain via a thioether bond and n is 8;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is trastuzumab connected from a cysteine side chain via a thioether bond and n is 5;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is trastuzumab connected from a cysteine side chain via a thioether bond and n is 6;
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is trastuzumab connected from a cysteine side chain via a thioether bond and n is 7; or
the targeting unit-linker-payload conjugate according to Formula VI, wherein T is trastuzumab connected from a cysteine side chain via a thioether bond and n is 8.
21 . A method for preparing the targeting unit-linker-payload conjugate of any preceding claim comprising conjugating the linker-payload conjugate of any preceding claim to a targeting unit, for example, an antibody, and optionally via a linker.
22 . A pharmaceutical composition comprising the linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate obtainable by the method of claim 21 .
23 . The pharmaceutical composition of claim 22 for use as a medicament or use in the treatment of cancer.
24 . A method of treating and/or modulating the growth of and/or prophylaxis of tumor cells in humans or animals, wherein the linker-payload conjugate of any preceding claim or the targeting unit-linker-payload conjugate of any preceding claim or the pharmaceutical composition of claim 22 is administered to a human or animal in an effective amount.
25 . The pharmaceutical composition of claim 22 or the method of claim 24 , wherein the cancer is selected from the group consisting of leukemia, lymphoma, breast cancer, prostate cancer, ovarian cancer, colorectal cancer, gastric cancer, squamous cancer, small-cell lung cancer, head-and-neck cancer, multidrug resistant cancer, glioma, melanoma and testicular cancer; and the tumor cells are selected from the group consisting of leukemia cells, lymphoma cells, breast cancer cells, prostate cancer cells, ovarian cancer cells, colorectal cancer cells, gastric cancer cells, squamous cancer cells, small-cell lung cancer cells, head-and-neck cancer cells, multidrug resistant cancer cells, and testicular cancer cells.Join the waitlist — get patent alerts
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