Patents Assigned to Synaffix B.V.
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Patent number: 11957763Abstract: 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: wherein: BM is a branching moiety; E is a capping group; SG is a sulfamide group; b, c, d, e, g, i, k, l 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.Type: GrantFiled: December 28, 2020Date of Patent: April 16, 2024Assignee: SYNAFFIX B.V.Inventors: Sander Sebastiaan Van Berkel, Ryan Heesbeen, Jorge Merijn Mathieu Verkade, Maria Antonia Wijdeven, Floris Louis Van Delft
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Patent number: 11951175Abstract: 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).Type: GrantFiled: February 8, 2017Date of Patent: April 9, 2024Assignee: Synaffix B.V.Inventors: Jorge Merijn Mathieu Verkade, Maria Antonia Wijdeven, Petrus Josephus Jacobus Maria Van De Sande, Remon Van Geel, Floris Louis Van Delft, Sander Sebastiaan Van Berkel
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Patent number: 11850286Abstract: 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 Q1 capable of reacting with a functional group F1 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: 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 Q1 of a linker-conjugate according to the invention with a functional group F1 of a biomolecule. The invention further relates to a bioconjugate obtainable by the process according to the invention.Type: GrantFiled: October 5, 2020Date of Patent: December 26, 2023Assignee: SYNAFFIX B.V.Inventors: Jorge Merijn Mathieu Verkade, Maria Antonia Wijdeven, Petrus Josephus Jacobus Maria Van De Sande, Sander Sebastiaan Van Berkel, Floris Louis Van Delft
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Publication number: 20230346965Abstract: 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.Type: ApplicationFiled: January 9, 2023Publication date: November 2, 2023Applicant: SynAffix B.V.Inventors: Jorge Merijn Mathieu VERKADE, Jorin HOOGENBOOM, Maria Antonia VAN BERKEL, Floris Louis VAN DELFT
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Patent number: 11713453Abstract: 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.Type: GrantFiled: December 7, 2020Date of Patent: August 1, 2023Assignee: SYNAFFIX B.V.Inventors: Remon Van Geel, Maria Antonia Wijdeven, Inge Catharina Josephina Hurkmans, Floris Louis Van Delft, Sander Sebastiaan Van Berkel
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Publication number: 20230127659Abstract: 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.Type: ApplicationFiled: May 20, 2022Publication date: April 27, 2023Applicant: SYNAFFIX B.V.Inventors: Sander Sebastiaan VAN BERKEL, Jorge Merijn Mathieu VERKADE, Maria Antonia WIJDEVEN, Ryan HEESBEEN, Petrus Josephus Jacobus Maria VAN DE SANDE, Remon VAN GEEL, Brian Maria Gerardus JANSSEN, Inge Catharina Josephina HURKMANS, Floris Louis VAN DELFT
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Publication number: 20230102685Abstract: 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.Type: ApplicationFiled: June 13, 2022Publication date: March 30, 2023Applicant: Synaffix B.V.Inventors: Floris Louis Van Delft, Floris Petrus Johannes Theodorus Rutjes, Frederik Jan Dommerholt
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Publication number: 20230100074Abstract: 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 ?-(1,4)-N-acetylgalactosaminyltransferase, with a non-natural sugar-derivative nucleotide. The non-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(O)OR8, —SC(S)OR8, —F, —Cl, —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.Type: ApplicationFiled: April 1, 2022Publication date: March 30, 2023Applicant: Synaffix B.V.Inventors: Sander Sebastiaan VAN BERKEL, Remon VAN GEEL, Maria Antonia WIJDEVEN, Floris Louis VAN DELFT
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Patent number: 11590239Abstract: 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.Type: GrantFiled: February 8, 2017Date of Patent: February 28, 2023Assignee: SYNAFFIX B.V.Inventors: Sander Sebastiaan Van Berkel, Jorge Merijn Mathieu Verkade, Maria Antonia Wijdeven, Ryan Heesbeen, Petrus Josephus Jacobus Maria Van De Sande, Remon Gvan Eel, Brian Maria Gerardus Janssen, Inge Catharina Josephina Hurkmans, Floris Louis Van Delft
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Patent number: 11358921Abstract: 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.Type: GrantFiled: March 19, 2019Date of Patent: June 14, 2022Assignee: SYNAFFIX B.V.Inventors: Floris Louis Van Delft, Floris Petrus Johannes Theodorus Rutjes, Frederik Jan Dommerholt
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Patent number: 11338043Abstract: The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found N that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index.Type: GrantFiled: February 8, 2017Date of Patent: May 24, 2022Assignee: SYNAFFIX B.V.Inventors: Sander Sebastiaan Van Berkel, Jorge Merijn Mathieu Verkade, Maria Antonia Wijdeven, Ryan Heesbeen, Petrus Josephus Jacobus Maria Van De Sande, Remon Van Geel, Brian Maria Gerardus Janssen, Inge Catharina Josephina Hurkmans, Floris Louis Van Delft
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Patent number: 11299759Abstract: 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 ?-(1,4)-N-acetylgalactosaminyltransferase, with a non-natural sugar-derivative nucleotide. The non-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(O)OR8, —SC(S)OR8, —F, —Cl, —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.Type: GrantFiled: May 4, 2018Date of Patent: April 12, 2022Assignee: SYNAFFIX B.V.Inventors: Sander Sebastiaan Van Berkel, Remon Van Geel, Maria Antonia Wijdeven, Floris Louis Van Delft
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Publication number: 20220096652Abstract: 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.Type: ApplicationFiled: December 1, 2021Publication date: March 31, 2022Applicant: Synaffix B.V.Inventors: Jorge Merijn Mathieu VERKADE, Arnoldus Jacobus VAN SCHAIK, Remon VAN GEEL, Maria Antonia WIJDEVEN, Sander Sebastiaan VAN BERKEL, Floris Louis VAN DELFT
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Publication number: 20220048920Abstract: 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: (i) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound comprises a substituent (ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group 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.Type: ApplicationFiled: October 15, 2021Publication date: February 17, 2022Applicant: SynAffix B.V.Inventors: Floris Louis VAN DELFT, Frederik Jan DOMMERHOLT
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Publication number: 20210353766Abstract: 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: wherein: BM is a branching moiety; E is a capping group; SG is a sulfamide group; b, c, d, e, g, i, k, l 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.Type: ApplicationFiled: December 28, 2020Publication date: November 18, 2021Applicant: SYNAFFIX B.V.Inventors: Sander Sebastiaan VAN BERKEL, Ryan HEESBEEN, Jorge Merijn Mathieu VERKADE, Maria Antonia WIJDEVEN, Floris Louis VAN DELFT
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Patent number: 11168085Abstract: 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: (i) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound comprises a substituent (ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group 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.Type: GrantFiled: January 26, 2015Date of Patent: November 9, 2021Assignee: SYNAFFIX B.V.Inventors: Floris Louis Van Delft, Frederik Jan Dommerholt
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Publication number: 20210332342Abstract: 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.Type: ApplicationFiled: December 7, 2020Publication date: October 28, 2021Applicant: Synaffix B.V.Inventors: Remon Van Geel, Maria Antonia WIJDEVEN, Inge Catharina Josephina HURMANS, Floris Louis Van Delft, Sander Sebastiaan Van Berkel
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Patent number: 11046988Abstract: The present invention relates to a process for the modification of a glycoprotein, using a ?-(1,4)-N-acetylgalactosaminyltransferase or a mutant thereof. The process comprises the step of contacting a glycoprotein comprising a glycan comprising a terminal GlcNAc-moiety, in the presence of a ?-(1,4)-N-acetylgalactosaminyltransferase 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(O)R3; —C?C—R4; —SH; —SC(O)R8; —SC(V)OR8, wherein V is O or S; —X wherein X is selected from the group consisting of F, Cl, Br and I; —OS(O)2R5; an optionally substituted C2-C24 alkyl group; an optionally substituted terminal C2-C24 alkenyl group; and an optionally substituted terminal C3-C24 alkenyl group.Type: GrantFiled: August 4, 2015Date of Patent: June 29, 2021Assignee: SYNAFFIX B.V.Inventors: Anna Agnieszka Wasiel, Floris Louis Van Delft, Sander Sebastiaan Van Berkel
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Publication number: 20210163623Abstract: 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.Type: ApplicationFiled: July 6, 2020Publication date: June 3, 2021Applicant: SynAffix B.V.Inventors: Floris Louis VAN DELFT, Remon Van Geel, Maria Antonia Wijdeven
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Publication number: 20210030886Abstract: 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 Q1 capable of reacting with a functional group F1 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: 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 Q1 of a linker-conjugate according to the invention with a functional group F1 of a biomolecule. The invention further relates to a bioconjugate obtainable by the process according to the invention.Type: ApplicationFiled: October 5, 2020Publication date: February 4, 2021Applicant: Synaffix B.V.Inventors: Jorge Merijn Mathieu VERKADE, Maria Antonia WIJDEVEN, Petrus Josephus Jacobus Maria VAN DE SANDE, Sander Sebastiaan VAN BERKEL, Floris Louis VAN DELFT