Compounds containing Fc binding units and conjugates prepared using the same

Abstract

Some embodiments of the present application provide compounds comprising an Fc-binding unit. These compounds can be used to regiospecifically transfer a group of interest to an antibody. Furthermore, some embodiments of the present application provide methods for preparing antibody conjugates comprising a group of interest (e.g., a reactive group) using these compounds.

Description

[Technical Field]

[0001] This application relates to compounds comprising an Fc-binding unit, conjugates prepared using the same, and methods for preparing conjugates using compounds comprising an Fc-binding unit. Compounds comprising an Fc-binding unit provided according to some embodiments of this application allow a component of interest (e.g., a reactive group) to be moved to a desired site on an antibody. That is, a component of interest can be site-specifically moved to an antibody by a compound comprising an Fc-binding unit.

[0002] Furthermore, the present invention provides an antibody-functional group conjugate (e.g., an antibody-drug conjugate) characterized by having a branched linker. [Background technology]

[0003] Antibodies are biomolecules that have the function of recognizing specific molecules and are used in a variety of industrial applications. For example, antibodies can be used for therapeutic purposes by detecting or searching for (selecting) specific components, identifying the pathways through which specific components move within the body or cells, and inducing an immune response to specific components.

[0004] Attempts have been made to improve such antibodies to extend their functionality. Typically, attempts have been made to label or conjugate antibodies with various components (e.g., drugs or radioactive substructures) to supplement or extend their functionality. Typically, antibodies may be labeled with a fluorescent component and used in fluorescence assays, or antibodies may be labeled with or conjugated with agents to treat specific diseases to maximize the therapeutic effect of the antibody. These attempts and techniques may be called antibody labeling or antibody-target substructure conjugates, and this application relates to antibody labeling or antibody-target substructure conjugates.

[0005] In previous studies, antibody-target substructure conjugates were prepared using highly reactive amino acid residues (e.g., amine or thiol groups) among the amino acid residues that make up the antibody. Specifically, a reactive group capable of reacting with the residue was introduced into the target substructure, and then a target substructure capable of reacting with the reactive residue of the antibody (more specifically, a modified target substructure with the reactive group introduced) was prepared. The antibody-target substructure conjugate was then prepared by reacting the modified target substructure with the antibody.

[0006] Previous studies like these involved randomly attaching target substructure components to antibodies, and these past methods had many problems.

[0007] Essentially, previous methods could not precisely control the "site" where the target substructure binds to the antibody, nor could they precisely control the "number" of target substructures that bind to the antibody. In other words, antibody-target substructure conjugates prepared by conventional methods suffer from the problem of heterogeneity in drug structure.

[0008] Such drug structural heterogeneity inevitably leads to heterogeneity in drug effects caused by "differences" in drug structure. These problems pose a significant obstacle to the development of antibody-drug conjugate (ADC) technologies, which require high safety and reproducibility.

[0009] Furthermore, the problem of drug structural heterogeneity leads to the problem of impaired antibody function. Antibodies contain a Fab region, which includes an antigen-binding domain that recognizes the antigen, and an Fc region, which is involved in antibody crystallization. Non-site-specific conjugates / labels make it impossible to precisely control the binding site of the target substructure to the antibody, making it impossible to prevent the target substructure from binding to the antibody's antigen-binding domain or a site adjacent to the antigen-binding domain, thereby interfering with the antibody's recognition function.

[0010] As a result, in this field, techniques for site-specific antibody labeling are required to ensure the structural uniformity of antibody-target substructure conjugates. Although several techniques have been developed, most of them lack technical and economic effectiveness, such as those involving genetic manipulation or modification of antibodies.

[0011] Under the circumstances described above, techniques for resitually transferring the group of interest to an antibody have been actively developed.

[0012] In particular, the document [Korean Patent Application No. 10-2020-0091826 (Application No. 10-2020-0009162)] discloses a technique for transferring a click chemical functional group, which is a component of interest, to an antibody using a compound containing an Fc-binding unit. Specifically, the document discloses a technique for site-specifically using a compound containing an Fc-binding unit to transfer a component of interest to an antibody, either by releasing the Fc-binding unit or with the Fc-binding unit. On the other hand, with respect to a compound containing an Fc-binding unit for transferring a component of interest to an antibody by releasing the Fc-binding unit, research results disclosed in this application by the inventors of this application have confirmed that the compound containing an Fc-binding unit disclosed in Korean Patent Application No. 10-2020-0091826 has several problems and is unsuitable for use. Accordingly, the inventors of the present application have developed a compound containing a novel Fc-bonding unit with improved effects, based on Patent Application No. 10-2020-0091826. [Overview of the project] [Problems that the invention aims to solve]

[0013] Methods have been developed to site-specifically transfer components of interest (e.g., reactive groups or functional groups) to antibodies using compounds containing Fc-binding units. However, this application has confirmed that when the compounds disclosed in Korean Patent Application No. 10-2020-0091826 are used, problems arise such as low yield of the conjugate product, excessively long reaction times, or inability to obtain the conjugate. Therefore, this application provides compounds containing Fc-binding units that have improved or enhanced effects (e.g., improved reaction efficiency). [Means for solving the problem]

[0014] This application provides a compound comprising an Fc-binding unit. The compound comprising the Fc-binding unit of this application may be used in the preparation of antibody conjugates.

[0015] Furthermore, the present application provides a method for preparing antibody conjugates (for example, antibody conjugates containing a group of interest or antibody conjugates containing a reactive group) using compounds comprising the Fc-binding unit of the present application.

[0016] Furthermore, the present application provides a method for preparing an antibody-payload conjugate using a compound, antibody, and payload comprising the Fc-binding unit of the present application; or an antibody conjugate and payload comprising the reactive group of the present application.

[0017] Furthermore, the present invention provides an antibody-payload conjugate comprising a branched linker having an improved or enhanced effect (e.g., improved plasma stability), and a method for preparing the same. [Effects of the Invention]

[0018] This application provides a compound comprising an Fc-bonded unit having an improved or enhanced effect (e.g., improved reaction efficiency).

[0019] Furthermore, the present application discloses an antibody-payload conjugate comprising a branched linker that has an improved or enhanced effect (e.g., improved plasma stability). [Brief explanation of the drawing]

[0020] [Figure 1] The positions of lysine residues on the Fc region, including lysine 246 and lysine 248, are illustrated. [Figure 2] This shows the positional relationship between the Fc-binding peptide and the Fc region. [Figure 3] This shows the positional relationship between the Fc-binding peptide and the Fc region. [Figure 4] Examples include lysine 246 and lysine 248 in the Xa1 and Fc regions of the Fc-binding peptide. [Figure 5] This relates to the distance between the amine group at lysine 246 in the Fc region and the beta carbon of Xa1 in the Fc-bound peptide. [Figure 6] This relates to the distance between the amine group of lysine 248 in the Fc region and the beta carbon of Xa1 in the Fc-bound peptide. [Figure 7] This invention illustrates the reaction of an antibody with a compound containing the Fc-binding unit of the present invention, and the antibody conjugate containing the group of interest prepared by the reaction. [Figure 8] We illustrate an antibody conjugate containing two groups of interest, where the two groups of interest are linked to K246 in the Fc region of the antibody. [Figure 9] We illustrate an antibody conjugate containing two groups of interest, where the two groups of interest are linked to K248 in the Fc region of the antibody. [Figure 10] We illustrate an antibody conjugate containing a group of interest in which one of the two groups of interest is linked to K246 and the other group of interest is linked to K248. [Figure 11] This invention relates to one embodiment of a method for preparing an antibody conjugate containing a group of interest. [Figure 12] Examples of antibodies and antibody units are shown. [Figure 13]This relates to one embodiment of a method for preparing antibody-payload conjugates. [Figure 14] The results of confirming the conjugate efficiency of compound 1 are shown. [Figure 15] The results of confirming the conjugate efficiency of compound 3 are shown. [Figure 16] The results of confirming the conjugate efficiency of compound 4 are shown. [Figure 17] The results of confirming the conjugate efficiency of compound 5 are shown below. [Figure 18] The results of confirming the conjugate efficiency of compounds 6 and 7 are shown. [Figure 19] The results of confirming the conjugate efficiency of compound 8 are shown. [Figure 20] The results of confirming the conjugate efficiency of compound 8 are shown. [Figure 21] The results of confirming the conjugate efficiency of compounds 6-8 under long-term reaction conditions are shown. [Figure 22] The results of examining the conjugate efficiency of each compound (compounds 6-8) when the reaction time between the compound and the antibody is 48 hours are shown. [Figure 23] A schematic diagram of the preparation of an antibody-payload conjugate using compound 9, anti-CLDN 18.2mAb, and payload 1 is shown. [Figure 24] A schematic diagram of the preparation of an antibody-payload conjugate using compound 9, anti-CLDN 18.2mAb, and payload 1 is shown. [Figure 25] The (PEG8)2-BG-MMAE substructure of the antibody-payload conjugate (DAR2) shown in Figure 24 is illustrated in detail. [Figure 26] The results of confirming the conjugate efficiency of compound 9 are shown. [Figure 27] The results of confirming the conjugate efficiency of compound 9 are shown. [Figure 28] The results of confirming the conjugate efficiency of compound 9 are shown. [Figure 29]The results of confirming the conjugate efficiency of compound 10 are shown. [Figure 30] The results of confirming the conjugate efficiency of compound 11 are shown. [Figure 31] The results of confirming the conjugate efficiency of compound 12 are shown. [Figure 32] The results of confirming the conjugate efficiency of compound 12 are shown. [Figure 33] The results of confirming the stability of compound 14 are shown. [Figure 34] This graph shows the absorbance measured after treating CHO-K1 cell lines (MOCK CHO-K1), which were transiently transfected with only a MOCK vector (empty vector), with antibody-A and ADC-A, respectively. [Figure 35] This graph shows the absorbance measured after treating CHO-K1 cell lines (Claudin18.1CHO-K1), which were transiently transfected with the gene encoding the claudin 18.1 protein (CLDN18.1) (SEQ ID NO: 29), with antibody-A and ADC-A, respectively. [Figure 36] This graph shows the absorbance measured after treating CHO-K1 cell lines (Claudin18.2CHO-K1), which were transiently transfected with the gene encoding the claudin 18.2 protein (CLDN18.2) (SEQ ID NO: 30), with antibody-A and ADC-A, respectively. [Figure 37] This graph shows the absorbance measured after treating CLDN18.2-virus-like particles (VLPs), which express the claudin 18.2 protein (CLDN18.2), with antibody-A and ADC-A, respectively. [Figure 38] This graph shows the absorbance measured after treating the MIA PaCa-2~CLDN18.2 cell line with antibody-A, ADC-A, antibody-B, and ADC-B, respectively. [Figure 39] This graph shows the absorbance measured after treating the SNU601 cell line with antibody-A, ADC-A, antibody-B, and ADC-B, respectively. [Figure 40]This graph shows the absorbance measured after treating the PATU8988S cell line with antibody-A, ADC-A, antibody-B, and ADC-B, respectively. [Figure 41] This graph shows the absorbance measured after treating the MIA PaCa-2 (CLDN18.2-) cell line with antibody-A, ADC-A, antibody-B, and ADC-B, respectively. [Figure 42] This graph shows the level of internalization measured hourly after treatment of the MIA PaCa-2~CLDN18.2 cell line with antibody-A and ADC-A, respectively. In this graph, the percentage of the red area on the cell axis represents the proportion of the area occupied by antibody-A or ADC-A that has penetrated the cell (area measured as red dots) out of the total area occupied by the cell. [Figure 43] This graph shows the level of internalization measured hourly after treatment of the MIA PaCa-2 (CLDN18.2-) cell line with antibody-A and ADC-A, respectively. In this case, the percentage of the red area on the cell axis represents the percentage of the area occupied by antibody-A or ADC-A that has penetrated the cell (measured as red dots). [Figure 44] This graph shows the level of internalization measured hourly after treatment of the SNU601 cell line with antibody-A and ADC-A, respectively. The red area on the cell axis represents the percentage of the total area occupied by the cell that is occupied by antibody-A or ADC-A (measured as red dots). [Figure 45] This graph shows the changes in cell viability after treatment of the MIA PaCa-2~CLDN18.2 cell line with various concentrations of antibody-A, ADC-A, antibody-B, ADC-B, and combinations of antibody-A and MMAE. [Figure 46] This graph shows the changes in cell viability of the PATU8988S cell line after treatment with various concentrations of antibody-A, ADC-A, antibody-B, ADC-B, and combinations of antibody-A and MMAE. [Figure 47]This graph shows the changes in cell viability of the SNU601 cell line after treatment with various concentrations of antibody-A, ADC-A, antibody-B, ADC-B, and combinations of antibody-A and MMAE. [Figure 48] This graph shows the changes in cell viability of the NUGC4 cell line after treatment with various concentrations of antibody-A, ADC-A, antibody-B, ADC-B, and combinations of antibody-A and MMAE. [Figure 49] This graph shows the changes in cell viability of the MIA PaCa-2 (CLDN18.2-) cell line after treatment with various concentrations of antibody-A, ADC-A, antibody-B, ADC-B, and combinations of antibody-A and MMAE. [Figure 50] This graph shows the changes in cell viability after AGS cell lines were treated with various concentrations of antibody-A, ADC-A, antibody-B, ADC-B, and combinations of antibody-A and MMAE. [Figure 51] This graph shows the relative proportion of total antibodies or total ADCs measured after extracting the supernatant from human plasma samples that have been treated with antibody-A, ADC-A, and ADC-B respectively and incubated for various time periods. [Figure 52] This graph shows the relative percentage of total antibodies or total ADCs measured after extracting the supernatant from samples treated with antibody-A, ADC-A, and ADC-B respectively, and incubated for various time periods. [Figure 53] This graph shows the relative percentage of total antibodies or total ADCs measured after extracting the supernatant from rat plasma samples that have been treated with antibody-A, ADC-A, and ADC-B respectively and incubated for various time periods. [Figure 54] This graph shows the relative percentage of total antibodies or total ADCs measured after extracting the supernatant from samples treated with antibody-A, ADC-A, and ADC-B respectively, and incubated for various time periods. [Figure 55]This graph shows the tumor volume measured after intravenous injection of antibody-A, ADC-A, and ADC-C into tumor model mice (groups G1-G8) under various conditions. [Figure 56] This graph shows the body weight measured after intravenous injection of antibody-A, ADC-A, and ADC-C into tumor model mice (groups G1-G8) under various conditions. [Figure 57] The images show comparative photographs of tumors dissected 28 days after intravenous injection of antibody-A, ADC-A, and ADC-C into tumor model mice (groups G1-G8) under various conditions. [Figure 58] This graph shows the weight of tumors dissected 28 days after intravenous injection of antibody-A, ADC-A, and ADC-C into tumor model mice (groups G1-G8) under various conditions. [Figure 59] This graph shows the total antibody and total ADC concentrations measured after a certain period of time following intravenous administration of ADC-A to rats at various concentrations. [Modes for carrying out the invention]

[0021] Some embodiments of the present application provide compounds comprising an Fc-binding unit.

[0022] Some embodiments of this application are given by formula 2-2: [Formula 2-2] [ka] The present invention provides a compound containing an Fc-bonding unit having the structure, During the ceremony, D a Spacer A is bonded to, substituted or unsubstituted C 1~20 Alkylene, substituted or unsubstituted C 1~20 Heteroalkylenes, substituted or unsubstituted C 2~20 Alkenylene, substituted or unsubstituted C 2~20 Heteroalkenylenes, substituted or unsubstituted C 2~20An alkynylene, or a substituted or unsubstituted C 2~20 heteroalkynylene, wherein substituted means that one or more hydrogen atoms in a group modified by the term substituted are substituted with one or more kinds of substituents, and wherein each of the substituents is independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, wherein each R is independently H, halogen, C 1~6 alkyl, C 3~10 cycloalkyl, C 3~10 heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH, and wherein the substituent is not H, and wherein heteroalkylene, heteroalkenylene, heteroalkynylene, heterocycloalkyl, or heteroaryl contains one or more heteroatoms, and each of the heteroatoms is independently selected from N, O, and S L a is linker A, and linker A is a bond, a substituted or unsubstituted C 1~100 alkylene, a substituted or unsubstituted C 1~100 heteroalkylene, a substituted or unsubstituted C 2~100 alkenylene, a substituted or unsubstituted C 2~100 heteroalkenylene, a substituted or unsubstituted C 2~100 alkynylene, or a substituted or unsubstituted C 2~100 heteroalkynylene, wherein substituted means that one or more hydrogen atoms in a group modified by the term substituted are substituted with one or more kinds of substituents, and wherein each of the substituents is independently selected from -R, =O, =S, -NO2, -CR3, -NR2, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, wherein each R is independently H, halogen, C 1~6 alkyl, C 3~10 cycloalkyl, C3~10 Selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH, wherein the substituent is not H, and wherein the heteroalkylene, heteroalkenylene, heteroalkylnylene, heterocycloalkyl, or heteroaryl contains one or more heteroatoms, each of which is independently selected from N, O, and S. X is -CH2-, -O-, or -NH-, R a1 is H or C 1~6 It is alkyl, R a2 is H or C 1~6 It is alkyl, R a3 is H or C 1~6 It is alkyl, J a These are -C(=O)-, -S-, -NH-, or -C(=NH)-, RG is a reactive group, and a reactive group includes a reactive substructure. FcBU is an Fc-binding unit, and an Fc-binding unit is [ka] It has a structure, During the ceremony, Each of Xaa is independently selected from any amino acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. The cysteine ​​residues adjacent to the N-terminus and the cysteine ​​residues adjacent to the C-terminus are optionally linked by covalent bonds. Xa 1 'teeth [ka] And, In the formula, m is an integer between 1 and 5. J f These are -NH-, -S-, or -C(=O)-, * and ** are each Xa 1 'Xa with adjacent amino acid residues 1 This represents the attachment point of ', *** is the Xa between the non-Fc bonded portion in a compound containing an Fc bonded unit. 1 This represents the attachment point.

[0023] In certain embodiments, X may be -O- or -CH2-.

[0024] In certain embodiments, X may be -O-.

[0025] In a particular embodiment, R a1 is C 1~3 Alkyl is also acceptable.

[0026] In a particular embodiment, R a1 It may also be methyl.

[0027] In a particular embodiment, R a2 and R a3 Each of these independently consists of H and C 1~3 It may be any one selected from alkyl groups.

[0028] In a particular embodiment, R a2 and R a3 Both can be H.

[0029] In a particular embodiment, J a It can also be -C(=O)-.

[0030] In a particular embodiment, D a is the unsubstituted C 1~10 Alkylene, unsubstituted C 1~10 heteroalkylene, unsubstituted C 2~10 Alkenylene or unsubstituted carbon 2~10 Heteroalkenylenes are also acceptable.

[0031] In a particular embodiment, D a is the unsubstituted C 1~10 Alkylene is also acceptable.

[0032] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have.

[0033] In a particular embodiment, J f -NH- is also fine.

[0034] In certain embodiments, m may be an integer from 1 to 4.

[0035] In certain embodiments, m may be 3.

[0036] In a particular embodiment, L a This is an unbonded, unsubstituted C. 1~60 Alkylene, unsubstituted C 1~60 heteroalkylene, unsubstituted C 2~60 Alkenylene or unsubstituted carbon 2~60 Heteroalkenylenes are also acceptable.

[0037] In a particular embodiment, L a This is an unbonded, unsubstituted C. 1~60 Alkylene or unsubstituted carbon 1~60 A heteroalkylene, which is an unsubstituted heteroalkylene, may contain 0 to 20 ethylene glycol units.

[0038] In a particular embodiment, L a This is an unbonded, unsubstituted C. 1~30 Alkylene or unsubstituted carbon 1~30A heteroalkylene, which is an unsubstituted heteroalkylene, may contain 0 to 10 ethylene glycol units.

[0039] In a particular embodiment, L a This is an unbonded, unsubstituted C. 1~24 Alkylene or unsubstituted carbon 1~24 A heteroalkylene, which is an unsubstituted heteroalkylene, may contain 0 to 8 ethylene glycol units.

[0040] In a particular embodiment, L a teeth [ka] In the formula, sf may be an integer between 0 and 8, sg may be an integer between 0 and 15, and sh may be an integer between 0 and 8. In a particular embodiment, sf may be an integer between 0 and 3, sg may be an integer between 0 and 10, and sh may be an integer between 0 and 3.

[0041] In a particular embodiment, RG has the following structure: [ka] It can be represented by, In the formula, D RG This is a spacer for the reactive group (spacer RG), The spacers of the reactive groups are bonded, substituted, or unsubstituted carbon atoms. 1~6 Alkylene, substituted or unsubstituted C 1~6 Heteroalkylenes, substituted or unsubstituted C 2~6 Alkenylene, or substituted or unsubstituted C 2~6 A heteroalkenylene, where substituted means that one or more hydrogen atoms in the group modified by the term substituted are substituted with one or more types of substituents, where each substituent is independently -C 1~4Selected from alkyl, -C(=O)H, -C(=O)NH2, -NH2, =NH, =O, =S, -OH, -NO2, and -SH, where a heteroalkylene or heteroalkenylene contains one or more heteroatoms, each of which is independently selected from O, N, and S. H RG This is a reactive substructure.

[0042] In certain embodiments, the reactive substructure may be a bioorthogonal functional group.

[0043] In a particular embodiment, the reactive substructure has the following structure: [ka] [ka] It may have any one of the following: During the ceremony, hn is an integer between 1 and 3. R H Each of these is independently selected from H, -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is independently selected from H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 Selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH.

[0044] In certain embodiments, the reactive substructure may be selected from an azide group, a terminal alkyne group, a terminal alkene group, a cyclooctin group, a tetrazine group, a norbornene group, a cyclooctene group, an oxime group, and an isocyanide group. The cyclooctin group may be any one selected from OCT cyclooctin, BCN (bicyclononine), DBCO (dibenzocyclooctin), DIBAC (aza-dibenzocyclooctin), DIBO (dibenzocyclooctinol), DIFO (difluorinated cyclooctin), BARAC (biarylazacyclooctinone), DIMAC (dimethoxyazacyclooctin), and DIFBO (difluorobenzocyclooctin). The cyclooctene group may be any one selected from a cis-cyclooctene group and a trans-cyclooctene group.

[0045] Some embodiments of this application are given by the following formula 2-15: [Formula 2-15] [ka] The present invention provides a compound containing an Fc-bonding unit having the structure, During the ceremony, aa is an integer between 1 and 10. X is -O- or -CH2-, L a This is linker A, and linker A is linked to, unsubstituted C 1~30 Unsubstituted C2, containing alkylene or 0-10 ethylene glycol units. 1~30 It is a heteroalkylene, [ka] is a reactive group, D RG The reactant spacer (spacer RG) is a bonded, substituted, or unsubstituted C 1~6 Alkylene, substituted or unsubstituted C 1~6 Heteroalkylenes, substituted or unsubstituted C 2~6An alkenylene, or a substituted or unsubstituted C 2~6 heteroalkenylene, wherein a substituted one means that one or more hydrogen atoms in a group modified by the term "substituted" are substituted by one or more kinds of substituents, and each of the substituents is independently selected from -C 1~4 alkyl, -C(=O)H, -C(=O)CH3, -C(=O)OH, -C(=O)NH2, -NH2, =NH, =O, =S, -OH, -NO2, and -SH, and wherein the heteroalkylene or heteroalkenylene contains one or more heteroatoms, and each of the heteroatoms is independently selected from O, N, and S, H RG is a reactive substructure, FcBU is an Fc binding unit, and the Fc binding unit is

Chemical formula

[0046] In certain embodiments, aa may be an integer from 1 to 6.

[0047] In certain embodiments, aa may be 3.

[0048] In certain embodiments, the Fc binding unit has the following structure:

Chemical formula

[0049] In certain embodiments, m may be 3.

[0050] In certain embodiments, the reactive substructure may be a bioorthogonal functional group.

[0051] In certain embodiments, the reactive substructure has the following structure:

Chemical formula

Chemical formula

[0052] In certain embodiments, the reactive substructure may be selected from an azide group, a terminal alkyne group, a terminal alkene group, a cyclooctin group, a tetrazine group, a norbornene group, a cyclooctene group, an oxime group, and an isocyanide group. The cyclooctin group may be any one selected from OCT cyclooctin, BCN (bicyclononine), DBCO (dibenzocyclooctin), DIBAC (aza-dibenzocyclooctin), DIBO (dibenzocyclooctinol), DIFO (difluorinated cyclooctin), BARAC (biarylazacyclooctinone), DIMAC (dimethoxyazacyclooctin), and DIFBO (difluorobenzocyclooctin). The cyclooctene group may be any one selected from a cis-cyclooctene group and a trans-cyclooctene group.

[0053] Some embodiments of the present invention provide methods for preparing antibody conjugates containing reactive groups.

[0054] Some embodiments of the present invention provide a method for preparing an antibody conjugate containing a reactive group, the method comprising the step of contacting a compound containing the Fc-binding unit of the present invention with an antibody, wherein the compound containing the Fc-binding unit has a reactive group.

[0055] In certain embodiments, the antibody may be an IgG antibody.

[0056] In certain embodiments, the antibody is an IgG antibody, which may be a human IgG antibody, a humanized IgG antibody, or a chimeric IgG antibody.

[0057] In certain embodiments, the Fc region of the antibody includes an amino acid sequence that comprises the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence that has 80% or more identity therewith, including the amino acid sequences of KPKDTLM (SEQ ID NO: 10) and MHEALHNHY (SEQ ID NO: 12).

[0058] In certain embodiments, following the step of contacting a compound containing an Fc-binding unit with an antibody, the reactive group is moved to a target region of the antibody, which consists of five consecutive amino acid residues and may include K246 and K248 of the antibody's Fc region.

[0059] In certain embodiments, following the step of contacting the compound containing the Fc binding unit with the antibody, the reactive group may be moved to one or more of K246 and K248 in the Fc region of the antibody.

[0060] In certain embodiments, a method for preparing an antibody conjugate containing a reactive group may further comprise the step of obtaining an antibody conjugate containing a reactive group.

[0061] In certain embodiments, an antibody conjugate containing reactive groups is prepared by contacting a compound containing an Fc-binding unit with an antibody, and the antibody conjugate containing reactive groups may contain 1 to 4 reactive groups.

[0062] In certain embodiments, an antibody conjugate containing a reactive group is prepared by contacting a compound containing an Fc-binding unit with an antibody. The antibody conjugate containing the reactive group contains two reactive groups. In an antibody conjugate containing a reactive group, one of the two reactive groups (the first reactive group) is linked to one of K246 and K248 of one of the two heavy chains of the antibody (the first heavy chain). In an antibody conjugate containing a reactive group, the other reactive group of the two reactive groups (the second reactive group) may be linked to one of K246 and K248 of the other heavy chain (the second heavy chain) of the antibody.

[0063] In certain embodiments, an antibody conjugate containing a reactive group is prepared by contacting a compound containing an Fc-binding unit with an antibody. The antibody conjugate containing the reactive group contains two reactive groups. Each of the two reactive groups may be linked to K246 of one heavy chain of the antibody and K246 of the other heavy chain, respectively, or to K248 of one heavy chain of the antibody and K248 of the other heavy chain, respectively.

[0064] In certain embodiments, the step of contacting a compound containing an Fc-binding unit with an antibody may be achieved by a method comprising the step of mixing a composition having a compound containing an Fc-binding unit with a composition having an antibody. In certain embodiments, the step of mixing a composition having a compound containing an Fc-binding unit with a composition having an antibody may be carried out under conditions of pH 6 to pH 8.5. [Mode of the invention]

[0065] The contents of the present invention will be described in more detail thereafter by means of embodiments and examples. The invention disclosed herein can be carried out in various forms and is not limited to the specific embodiments described herein.

[0066] A person skilled in the art in the field to which the invention disclosed herein pertains will be able to conceive of various modifications and other embodiments of the invention disclosed herein. Therefore, it should be understood that the invention disclosed herein is not limited to the specific embodiments or examples described herein, and that such modifications and other embodiments are also included within the invention disclosed herein.

[0067] Explanation of terms Unless otherwise stated, all technical and scientific terms used in this application have the same meaning as those generally understood by those skilled in the art to which this application pertains. All publications, patents and other references referenced herein are cited by reference in their entirety.

[0068] "Halogen" or "halo" refers to groups containing fluorine, chlorine, bromine, and iodine, which are elements in the halogen group of the periodic table.

[0069] As used herein, the term “hetero” refers to a compound or group containing one or more heteroatoms. That is, the term “hetero” can be used in conjunction with terms used to refer to a molecule itself or a part of a molecule. For example, heteroalkylene refers to an alkylene group containing one or more heteroatoms in its main chain. Another example is heteroaryl, which refers to an aryl group containing one or more heteroatoms on the ring (e.g., a C6 aryl group in which one or more carbon atoms on the ring are each substituted with independently selected heteroatoms). The term “heteroatom” refers to an atom other than carbon or hydrogen, including, for example, B, Si, N, P, O, S, F, Cl, Br, I, and Se. Preferably, this term includes polyvalent elements such as N, O, and S. For example, if the structure contains one or more heteroatoms, each heteroatom may be independently selected from N, O, and S.

[0070] The terms “alkyl” or “alkane,” used to refer to a molecule itself or a part of a molecule, are used to mean a fully saturated linear or branched hydrocarbon group. Linear and branched alkyl groups include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl. Alkyl groups may also include cyclic structures. x~y The term "C" is intended to refer to a chain or ring containing a residue with x to y carbon atoms, for example, when used together with the term alkyl. x~y The term "alkyl" may mean an alkyl group containing x to y carbon atoms, whether substituted or unsubstituted linear alkyl groups, branched alkyl groups, or alkyl groups containing a cyclic structure. C0 alkyl group means hydrogen. 1~4 Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, and isobutyl. For example, linear or branched alkyl groups may have 1 to about 60, 1 to 20, or 1 to 10 carbon atoms.

[0071] As used herein, the term "heteroalkyl" refers to an alkyl group containing one or more heteroatoms, where each heteroatom is selected independently.

[0072] The term “alkylene,” used to refer to a molecule itself or a part of a molecule, means a divalent radical derived from an alkyl group. The term “alkylene” may be used with the terms “substituted” or “unsubstituted,” as needed. If the term “alkylene” is not used with the terms “substituted” or “unsubstituted,” the term “alkylene” is intended to encompass both substituted and unsubstituted forms of alkylene. For example, alkylene may refer to a group having 1 to 100 carbon atoms in its main chain. Examples of alkylene may include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, and -CH2CH2CH2CH2-. For example, alkylene may be used as C2 alkylene, referring to an alkylene group having 2 carbon atoms in its main chain. Exemplary, “C x~y The term "alkylene" is used herein to mean an alkylene having x to y carbon atoms in its main chain, whether substituted or unsubstituted.

[0073] The term “heteroalkylene,” used to refer to the molecule itself or to a part of the molecule, means a divalent radical derived from a heteroalkyl group. The term “heteroalkylene” may be used with the terms “substituted” or “unsubstituted,” as needed. If the term “heteroalkylene” is not used with the terms “substituted” or “unsubstituted,” the term “heteroalkylene” is intended to encompass both substituted and unsubstituted heteroalkylene forms. For example, a heteroalkylene may refer to a group having 1 to 100 carbon atoms and heteroatoms in the main chain (e.g., the total number of carbon atoms and heteroatoms in the main chain is between 1 and 100). Examples of heteroalkylene groups include, but are not limited to, -CH2-CH2-O-CH2-CH2- and -CH2-O-CH2-CH2-NH-CH2-. A heteroalkylene group may contain one or more heteroatoms, each of which may be the same or different. For example, a heteroalkylene group may contain one or more heteroatoms at positions other than the ends of a chain or branch, and each heteroatom may be the same or different. For example, a heteroalkylene group may contain one or more heteroatoms at each end of a chain or branch, or at all ends of a chain or branch, and each heteroatom may be the same or different. Exemplarily, "C" in this specification x~y The term "heteroalkylene" is used to refer to a heteroalkylene having a total of x to y atoms in the main chain, whether substituted or unsubstituted (for example, the sum of the number of carbon atoms and heteroatoms in the main chain is x to y). For example, C3 heteroalkylene may be used to mean a heteroalkylene having two carbon atoms and one heteroatom in the main chain. As another example, C5 heteroalkylene may be used to mean a heteroalkylene having three carbon atoms and two heteroatoms in the main chain. C5 heteroalkylenes include structures such as -CH2-CH2-O-CH2-CH2- and -CH2-O-CH2-NH-CH2-.

[0074] The term "cycloalkyl" is used to refer to a fully saturated cyclic hydrocarbon group. "Cycloalkyl" includes monocyclic and polycyclic groups. Unless otherwise defined, monocyclic cycloalkyl groups generally have 3 to about 20, preferably 3 to 10, carbon atoms on the ring. The rings other than the first ring in a polycyclic cycloalkyl group may be selected from saturated, unsaturated, and aromatic rings. Cycloalkyls include bicyclic molecules in which 1, 2, or 3 or more atoms are shared between two rings. The term "fusion cycloalkyl" refers to a polycyclic cycloalkyl group in which each ring shares two adjacent atoms with the other ring. The rings other than the first ring in a fusion polycyclic cycloalkyl group may be selected from saturated, unsaturated, and aromatic rings. Cycloalkyl may also be used with the terms substituted or unsubstituted, where substituted cycloalkyl refers to a group provided when one or more hydrogen atoms linked to carbon atoms on the ring are substituted with one or more independent substituents. Furthermore, the term cycloalkyl may also be used with the term heterocycloalkyl, which refers to a cycloalkyl group containing one or more heteroatoms on the ring.

[0075] The term "cycloalkylene" is used to mean a divalent radical derived from a cycloalkyl group. For example, the term cycloalkylene may be used with the terms substituted or unsubstituted. For example, the term cycloalkylene may be used with the term hetero.

[0076] The terms “alkene” or “alkenyl,” used to refer to a molecule itself or a part of a molecule, include one or more double bonds as a straight-chain or branched non-aromatic hydrocarbon. For example, a straight-chain or branched alkenyl group may have 2 to about 60, 2 to 20, or 2 to 10 carbon atoms.

[0077] The terms "heteroalkene" or "heteroalkenyl" refer to an alkenyl containing one or more heteroatoms. In this case, the heteroatoms are selected independently.

[0078] The term “alkenylene,” used to refer to the molecule itself or to a part of the molecule, means a divalent radical derived from an alkenyl. The term “alkenylene” may be used with the terms “substituted” or “unsubstituted,” as needed. When the term “alkenylene” is not used with the terms “substituted” or “unsubstituted,” the term “alkenylene” is intended to encompass both substituted and unsubstituted forms of alkenylene. For example, an alkenylene may refer to a group having 2 to 100 carbon atoms in the main chain. Examples of alkenylenes may include, but are not limited to, -C=C-, -CCC=CC=C-, or -CCCC=C-, etc. In this specification, “C x~y When used with "Alkenylene", C x~y The term "alkenylene" is used to refer to alkenylenes having x to y carbon atoms in their main chain, whether substituted or unsubstituted.

[0079] The term “heteroalkenylene,” used to refer to the molecule itself or to a part of the molecule, means a divalent radical derived from a heteroalkenyl. For example, the term “heteroalkenylene” may be used to refer to an alkenylene group containing one or more heteroatoms in the main chain. For example, heteroalkenylene may refer to a group having 2 to 100 carbon atoms and heteroatoms in the main chain (e.g., the total number of carbon atoms and heteroatoms is 2 to 100). The term “heteroalkenylene” may be used with the terms “substituted” or “unsubstituted” as needed. In this specification, “C x~y When used with heteroalkenylene, C x~y The term heteroalkenylene is used to refer to heteroalkenylenes that have x to y carbon atoms and heteroatoms in their main chain, whether substituted or unsubstituted (for example, the sum of the number of carbon atoms and heteroatoms is x to y).

[0080] The terms "cycloalkene" or "cycloalkenyl" refer to cyclic hydrocarbons containing one or more double bonds on a ring. "Cycloalkenyls" include monocyclic and polycyclic groups. Unless otherwise defined, monocyclic cycloalkenyl groups generally have 3 to about 20, preferably 3 to 10, carbon atoms on the ring. The rings other than the first ring in polycyclic cycloalkenyls may be selected from saturated, unsaturated, and aromatic rings. Cycloalkenyls include bicyclic molecules in which one, two, or three or more atoms are shared between two rings. The term "fusion cycloalkenyl" refers to a polycyclic cycloalkenyl in which each ring shares two adjacent atoms with the other ring. The rings other than the first ring in fusion polycyclic cycloalkenyls may be selected from saturated, unsaturated, and aromatic rings. The term "cycloalkenyl" may also be used with the terms "substituted" or "unsubstituted," where a substituted cycloalkenyl refers to a group provided when one or more hydrogen atoms linked to a carbon atom on the ring are substituted with one or more independent substituents. Furthermore, the term "cycloalkenyl" may also be used with the term "hetero," where a heterocycloalkenyl refers to a cycloalkenyl group containing one or more heteroatoms on the ring.

[0081] The term "cycloalkenylene" is used to mean a divalent radical derived from a cycloalkenyl. For example, the term cycloalkenylene may be used with the terms substituted or unsubstituted. For example, the term cycloalkenylene may be used with the term hetero.

[0082] The terms “alkyne” or “alkynyl,” used to refer to a molecule itself or a part of a molecule, include one or more triple bonds as a linear or branched non-aromatic hydrocarbon. For example, a linear or branched alkynyl group may have 2 to about 60, 2 to 20, or 2 to 10 carbon atoms.

[0083] The terms "heteroalkynyl" or "heteroalkynyl" refer to an alkynyl compound containing one or more heteroatoms. In this case, the heteroatoms are selected independently.

[0084] The term “alkynylene,” used to refer to the molecule itself or to a part of the molecule, means a divalent radical derived from alkynyl. The term “alkynylene” may be used with the terms “substituted” or “unsubstituted,” as needed. If the term “alkynylene” is not used with the terms “substituted” or “unsubstituted,” the term “alkynylene” is intended to encompass both substituted and unsubstituted forms of alkynylene. For example, alkynylene may refer to a group having 2 to 100 carbon atoms in the main chain. In this specification, “C x~y When used with "alkynylene", C x~y The term "alkynylene" is used to refer to alkynylenes having x to y carbon atoms in the main chain, whether substituted or unsubstituted.

[0085] The term “heteroalkylynylene,” used to refer to the molecule itself or to a part of the molecule, means a divalent radical derived from a heteroalkylyl. For example, the term “heteroalkylynylene” may be used to refer to an alkylylene group containing one or more heteroatoms in the main chain. For example, heteroalkylynylene may refer to a group having 2 to 100 carbon atoms and heteroatoms in the main chain (e.g., the total number of carbon atoms and heteroatoms in the main chain is 2 to 100). The term “heteroalkylynylene” may be used with the terms “substituted” or “unsubstituted,” as needed. In this specification, “C x~y When used with heteroalkylene, C x~y The term heteroalkylene is used to refer to a heteroalkylene having x to y carbon atoms and heteroatoms in its main chain, whether substituted or unsubstituted (for example, the sum of the number of carbon atoms and heteroatoms is x to y).

[0086] The term "cycloalkyne" or "cycloalkynyl" refers to a cyclic hydrocarbon containing one or more triple bonds on the ring, also known as a "strained alkyne." "Cycloalkynyls" include monocyclic and polycyclic groups. Unless otherwise defined, monocyclic cycloalkynyls generally have 3 to about 10 carbon atoms on the ring. The rings other than the first ring in a polycyclic cycloalkynyl may be selected from saturated, unsaturated, and aromatic rings. Cycloalkynyls include bicyclic molecules in which 1, 2, or 3 or more atoms are shared between two rings. The term "fusion cycloalkynyl" refers to a polycyclic cycloalkynyl in which each ring shares two adjacent atoms with the other ring. The rings other than the first ring in a fusion polycyclic cycloalkynyl may be selected from saturated, unsaturated, and aromatic rings. The term "cycloalkynyl" may be used with the terms "substituted" or "unsubstituted," where a substituted cycloalkynyl refers to a group provided when one or more hydrogen atoms linked to a carbon atom on the ring are substituted with one or more independent substituents. Furthermore, the term "cycloalkynyl" may be used with the term "hetero," where a heterocycloalkynyl refers to a cycloalkynyl group containing one or more heteroatoms on the ring.

[0087] The term "cycloalkylylene" is used to mean a divalent radical derived from cycloalkylyl. For example, the term cycloalkylylene may be used with the terms substituted or unsubstituted. For example, the term cycloalkylylene may be used with the term hetero.

[0088] The term "aryl" is used to refer to a group containing an aromatic ring, and specifically to a group derived from an aromatic compound, an arene. The term aryl includes monocyclic and polycyclic groups. The term "aryl" may also be used with the term "hetero," where heteroaryl is used to refer to an aryl group having one or more heteroatoms on the ring. The term "aryl" may also be used with the terms "substituted" or "unsubstituted," where substituted aryl refers to an aryl group in which one or more hydrogen atoms bonded to a carbon atom on the ring are substituted with one or more types of substituents. The term "aryl" may also be used to encompass both substituted and unsubstituted aryls, and substituted and unsubstituted heteroaryls. Examples of aryls include, but are not limited to, phenyl, pyridyl, naphthyl, and biphenyl.

[0089] The term "arirene" is used to mean a divalent radical derived from an aryl group. For example, the term arirene may be used with the terms substituted or unsubstituted. For example, the term arirene may be used with the term hetero. The term "arirene" may be used to encompass all substituted and unsubstituted arirenes, and substituted and unsubstituted heteroarirenes.

[0090] As used herein, the term “substituted” means that, if the valence of the atom is normal and the substituted compound is stable, one or more hydrogen atoms on an atom are substituted with substituents including deuterium and hydrogen variants. If the substituent is oxygen (i.e., =O), this means that two hydrogen atoms are substituted. If the substituent is a halogen (e.g., Cl, F, Br, and I), this means that one hydrogen atom is substituted with a halogen. If two or more substituents are present on a single group, the substituents present on that group may be the same or different. Unless otherwise specified, the type and number of substituents may be arbitrary, as long as it is chemically achievable. Exemplary substituents may be selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The substituents may be independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH (provided the substituent is not -H). A typical example of a substituent is -C 1~4 This includes, but is not limited to, alkyl, -C(=O)H, -C(=O)CH3, -C(=O)OH, -C(=O)NH2, -NH2, =NH, =O, =S, -OH, -NO2, and -SH. The terms substituted or unsubstituted may be used in conjunction with terms used to refer to the molecule itself or to a part of the molecule. For example, substituted C 10~20 Alkylene can mean that one or more hydrogen atoms linked to the main chain are substituted with substituents, and each substituent may be independently selected.

[0091] In this specification, when representing the structure (partial structure) of a compound, when representing a part to which another group and the groups of the partial structure are linked, a wavy line drawn in a direction approximately perpendicular to the bond is used (for example, [ka] ) is used. For example, structure [ka] When expressed as such, it indicates that an X group in a component, molecule, or compound is linked to another part by a bond. For example, structure [ka] When expressed as such, it indicates that the X group in a component, molecule, or compound is linked to other parts by a bond. For example, in a compound having the structure "AX", if only the structure of the X group is shown, it indicates that the structure [ka] It can be expressed as follows. For example, in a compound having the structure "AXB", if only the structure of X is given as an example, it can be expressed as follows: [ka] It can be represented as follows. If necessary, a wavy line drawn approximately perpendicular to the bond may be represented by additional notation. For example, in a compound having the structure AXB, if only the structure of the X group is exemplified, the structure of the X group is, [ka] This can be illustrated as an example, and if necessary, information can be provided about which part each wavy line represents a connection to by mentioning, for example, "* is a part connected to A, and ** is a part connected to B."

[0092] Furthermore, the wavy lines drawn in a direction nearly perpendicular to the bonds indicate that the "structure illustrated by the wavy lines" is directly covalently bonded to the "bases other than the structure illustrated by the wavy lines." The wavy lines should not be interpreted as meaning that other additional elements may be included between the "structure illustrated by the wavy lines" and the "bases other than the structure illustrated by the wavy lines." If additional elements are included, they will be explained by separate, relevant descriptions. The following structure is illustrated as an example.

[0093] -Example A [Example A] [ka] , In the formula, FcBU is an Fc-bonding unit, and the Fc-bonding unit has the following structure: [ka] It holds.

[0094] In this case, Xa 1 ' is, J a It is interpreted as being directly linked to (i.e., Xa 1 'and J a J a and Xa 1 (These are concatenated without any additional elements between them.)

[0095] Based on the above explanation, the structure of formula example A is as follows: [Formula example A-1] [ka] The following is an example.

[0096] -Example B [Example B] [ka] , In the formula, GOI is the desired group, the desired group is the reactant, and the reactant has the following structure: [ka] It holds.

[0097] In this case, D RG L a It is interpreted as being directly linked to (i.e., D RG and L a D RG and L a (They are linked without any additional elements between them.)

[0098] Based on the above explanation, the structure of formula example B is as follows: [Example B-1] [ka] The following is an example.

[0099] Structures used in structures or formulas disclosed herein [ka] " is C x It is used to mean alkylene. For example, structure [ka] This can be used to represent C4 alkylenes such as -CH2-CH2-CH2-CH2-. In this, if x is 0, it means a bond. That is, structure [ka] is structure [ka] It can be represented by:

[0100] The compounds disclosed herein may have specific geometric or stereoisomeric forms. Where a compound is disclosed without designation, isomers such as cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereoisomers, (D)-isomers, (L)-isomers, and racemates of the compound are included within the scope of this application. That is, any formula or structure disclosed herein that is associated with an isomer (e.g., [ka] , [ka] , and [ka] If it does not have (etc.), it means that the disclosed formula or structure includes all possible isomers.

[0101] As used herein, the term “amino acid” may be used to refer to both amino acids that are not bound to other amino acids and amino acid residues that are bound to other amino acids in proteins or peptides, and may be interpreted as appropriate according to the content or context of the paragraph in which the term “amino acid” is used. As used herein, the term “amino acid” may be used to include both natural and non-natural amino acids. As used herein, natural amino acids refer to the 20 amino acids that are synthesized in the human body through gene transcription and translation. Specifically, natural amino acids include alanine (Ala, A), arginine (Arg, R), asparagine (Asn, N), aspartic acid (Asp, D), cysteine ​​(Cys, C), glutamic acid (Glu, E), glutamine (Gln, Q), glycine (Gly, G), histidine (His, H), isoleucine (Ile, I), leucine (Leu, L), lysine (Lys, K), methionine (Met, M), phenylalanine (Phe, F), proline (Pro, P), serine (Ser, S), threonine (Thr, T), tryptophan (Trp, W), tyrosine (Tyr, Y), and valine (Val, V). As used herein, non-natural amino acids mean amino acids that are not synthesized in the human body by gene transcription and translation, but are synthesized by processes other than transcription and translation, or are artificially synthesized, or can be synthesized by other organisms other than humans. Non-natural amino acids may include, for example, ornithine (Orn), diaminopropionic acid (Dap), diaminobutyric acid (Dab), and naphthylalanine. As stated above, the term “amino acid” as used herein may be used to refer to both amino acids that are not bound to other amino acids, and amino acid residues that are bound to other amino acids contained in proteins or peptides. For example, alanine may be used to refer to alanine and / or an alanine residue. For example, arginine may be used to refer to arginine and / or an arginine residue. As used herein, the term “amino acid” may be used to include both L-type and D-type amino acids.In some embodiments, if there is no reference to L-type or D-type, the amino acid may be interpreted as an L-type amino acid.

[0102] As used herein, the term “amino acid residue” refers to a structure derived from an amino acid contained in a compound, peptide, and / or protein (e.g., an antibody) that is covalently linked to other parts of the compound, peptide, and / or protein. For example, when alanine, arginine, and glutamic acid are linked by an amide bond to form a peptide having an ARE sequence, the peptide contains three amino acid residues, and A, R, and E may be called the alanine residue, the arginine residue, and the glutamic acid residue, respectively. Furthermore, as described above, in a peptide having an ARE sequence, the peptide may contain three amino acids, and A, R, and E may also be called alanine, arginine, and glutamic acid, respectively. As another example, when aspartic acid, phenylalanine, and lysine are linked by an amide bond to form a peptide having a DFK sequence, the peptide contains three amino acid residues, and D, F, and K may be called the aspartic acid residue, the phenylalanine residue, and the lysine residue, respectively. Furthermore, as described above, in a peptide having a DFK sequence, the peptide may contain three amino acids, where D, F, and K may also be called aspartic acid, phenylalanine, and lysine, respectively.

[0103] Unless otherwise stated, when amino acid sequences are described herein, single-letter or three-letter notation is used, and the sequence is described in the direction from the N-terminus to the C-terminus. For example, when represented as RNVP, it refers to a peptide in which arginine, asparagine, valine, and proline are sequentially linked from the N-terminus to the C-terminus. Another example is when represented as Thr-Leu-Lys, it refers to a peptide in which threonine, leucine, and lysine are sequentially linked from the N-terminus to the C-terminus. For amino acids that cannot be represented by single-letter notation, other letters are used to describe these amino acids and are explained by additional notation.

[0104] As used herein, the term “click chemistry” refers to a chemical concept introduced by K. Barry Sharpless of the Scripps Research Institute to describe complementary chemical functional groups and chemical reactions designed to enable two molecules to rapidly and stably form a covalent bond. As used herein, click chemistry does not imply a specific reaction, but rather the concept of a fast and stable reaction. In one embodiment, several conditions should be satisfied for intermolecular bonding to occur by click chemistry. These conditions include high yield, excellent selectivity to reactive sites, modular work for organically assembling molecules, and proceeding in a thermodynamically stabilized direction for fast and accurate product production. The click chemistry described herein involves the reaction of mutually reactive pairs of click chemical functional groups (including, for example, terminal alkynes, azides, strained alkynes, dienes (e.g., Diels-alderdiene), dienophiles (e.g., Diels-alderdienophile), trans-cyclooctene, alkenes, thiols, tetrazines, triazines, dibenzocyclooctin (DBCO), and bicyclononines (including bicyclo[6.1.0]nona-4-yne)). Examples of click chemical reactions include Huisgen 1,3-dipolar cycloaddition (see Tornoe et al., Journal of Organic Chemistry (2002) 67:3075-3064, etc.); Diels-Alder reactions; reverse electron-demanded Diels-Alder reactions; nucleophilic addition to small, strained rings such as epoxides and aziridines; nucleophilic addition to activated carbonyl groups; Staudinger ligation; and addition reactions to carbon-carbon double or triple bonds.

[0105] The term "biotherthogonal functional group" is used to refer to a chemically reactive group that is biologically inert. That is, the term "biotherthogonal functional group" is used to refer to a chemical functional group that participates in and performs a bioorthogonal reaction in bioorthogonal chemistry or bioorthogonal reactions. The term "biotherthogonal functional group" may also be called a bioorthogonal chemical functional group or bioorthogonal chemical group. A bioorthogonal functional group refers to a group that does not react with functional groups in endogenous molecules or living cells or organisms. These bioorthogonal functional groups are designed to react with specific groups in complex biological systems without interfering with normal cellular processes. The term "biotherthogonal chemistry" was first proposed by Carolyn R. Bertozzi in 2003, and bioorthogonal chemistry remains widely used in the fields of organic chemistry and conjugates. The term "biotherthogonal" refers to the fact that chemical reactions carried out by bioorthogonal functional groups can occur without interfering with natural biological processes. One of the main characteristics of bioorthogonal functional groups is that they react specifically and efficiently with their corresponding reactive groups in a biological environment. Bioorthogonal functional groups, bioorthogonal chemistry, or bioorthogonal reactions are discussed in the following literature: [Sletten, Ellen M., and Carolyn R. Bertozzi, "Bioorthogonal chemistry: fishing for selectivity in a sea of ​​functionality," Angewandte Chemie International Edition 48.38(2009):6974-6998.; Mbua, Ngalle Eric, et al., "Strain-promoted alkyne-azide cycloadditions (SPAAC) reveal new features of glycoconjugate biosynthesis," ChemBioChem 12.12(2011):1912-1921.; Bird, Robert E. et al., "Bioorthogonal chemistry and its applications," Bioconjugate Chemistry 32.12(2021):2457-2479.]This is described in detail in Devaraj, Neal K, "The future of bioorthogonal chemistry," ACS Central Science 4.8 (2018):952-959; and Scinto, Samuel L. et al., "Bioorthogonal chemistry," Nature Reviews Methods Primers 1.1 (2021):30. All of these are cited herein by reference. Bioorthogonal chemistry can overlap significantly with the broader field of Crick chemistry. In certain embodiments, the term bioorthogonal functional group may be used to refer to a chemical group that is not reactive with antibodies but is capable of bioorthogonal reactions. Typical types of bioorthogonal reactions (or bioorthogonal chemistry) include, but are not limited to, copper-free azide-alkyne cyclization, tetrazine ligation, tetrazole ligation, oxime ligation, and isocyanide click reactions, as well as copper-free azide-alkyne cyclization, including Staudinger ligation, copper-catalyzed azide-alkyne cyclization (CuAAC), and strain-accelerated azide-alkyne cyclization (SPAAC). Bioorthogonal functional groups include, but are not limited to, azide, terminal alkyne, cyclic alkyne (e.g., cyclooctyne), tetrazine, norbornene, cycloalkene (e.g., cyclooctene), tetrazole, oxime, or isocyanide groups. For example, in copper-free azide-alkyne cyclization (strain-accelerated azide-alkyne cyclization; SPAAC), the azide group and the cyclooctyne group undergo bioorthogonal reactions. The cyclooctin group involved in SPAAC may be monocyclic cyclooctin or polycyclic cyclooctin, including fusion polycyclic groups. Specific examples of cyclooctin groups involved in SPAAC include, but are not limited to, bicyclononine (BCN), dibenzocyclooctin (DBCO), aza-dibenzocyclooctin (DIBAC), dibenzocyclooctinol (DIBO), difluorinated cyclooctin (DIFO), biarylazacyclooctinone (BARAC), dimethoxyazacyclooctin (DIMAC), and difluorobenzocyclooctin (DIFBO).

[0106] As used herein, the term antibody is used to refer to an immunoglobulin molecule or a fragment thereof. Immunoglobulins are typically well known and possess the ability to specifically bind to one or more antigens. As used herein, the term antibody is also used to encompass fragments thereof, and therefore it is not a problem if they do not possess the ability to bind to specific antigens, as in the case of Fc fragments. Unless used with specific limitations in relation to antibodies, the term antibody may be interpreted without specific limitations to include all monospecific antibodies, bispecific antibodies, trispecific antibodies, monoclonal antibodies, human antibodies, humanized antibodies, recombinant antibodies, and chimeric antibodies. For example, an antibody may consist of two heavy chains and two light chains. For example, in this case, it is known that an antibody may have structures in which two heavy chains are linked by one or more bridges (e.g., disulfide bonds), one heavy chain and one light chain are linked by one or more bridges, and another heavy chain and another light chain are linked by one or more bridges. An antibody may be divided into an Fc region (or Fc domain) and a Fab region, the Fab region containing a site capable of binding to an antigen, and the Fc region containing a portion of the constant region of the heavy chain. As used herein, the term “antibody” may be used to include both conjugated antibodies and unconjugated antibodies (e.g., free antibodies).

[0107] In this specification, the term "active substructure" is used to refer to one or more functional or active substructures. Active substructures may include, but are not limited to, drugs (e.g., toxins), imaging substructures (e.g., fluorescent substructures and luminescent substructures containing luminescent components such as luciferin), radioactive substructures, proteins with specific functions, affinity substances (e.g., biotin, streptavidin, and aptamers), stabilizing components, vitamins, nucleic acids (DNA or RNA), or polyethylene glycol (PEG) substructures. In this case, one or more active substructures may be selected independently. In some embodiments of this application, the active substructure may be contained within a functional group. Furthermore, in some embodiments of this application, the active substructure may be contained within a payload.

[0108] As used herein, the term “radioactive substructure” refers to a substructure containing a ligand for a radioisotope designed to bind to a radioisotope and / or a substructure containing a radioisotope (e.g., a radiometallic nuclide). The ligand for the radioisotope may be called, for example, a chelating agent. The chelating agent may be selected from, but is not limited to, tetraxetan (DOTA), 2,2',2"-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA), diethylenetriaminepentaacetic acid (DTPA), and ethylenediaminetetraacetic acid (EDTA). Radiolabeling is useful in imaging, radioimmunotherapy (RIT), and radiotherapy, among others. Radioactive substructures are, for example, 18 F, 11 C, 67 Cu, 90 Y, 125 I, 123 I, 124 I, 131 I, 177 Lu, 186 Re, 188 Re, 211 At, 213 Bi, 225 Ac, or 99m It may include, but is not limited to, Tc.

[0109] As used herein, the term “fluorescent substructure” refers to a substructure including a dye, protein, or staining reagent for use in fluorescent applications. Molecules that can be used as dyes and staining reagents are widely known in the art. Fluorescent substructures may include, but are not limited to, green fluorescent protein (GFP), Cy3, Cy5, Texas Red, FITC, rhodamine, or DAPI.

[0110] As used herein, the terms “drug” or “drug substructure” are used to mean a molecule or part of a molecule that has therapeutic efficacy against any disease. Drugs according to this application include those known to those skilled in the art to be effective against any disease. Furthermore, as used herein, the term “drug” may be used to include both conjugated drugs and unconjugated drugs (e.g., free drugs). Drugs include, for example, auristatin, eribulin, tubulicin, geldanamycin (Kerr et al., 1997, Bioconjugate Chem. 8(6):781-784), mytansinoids (EP1391213, ACR 2008, 41, 98-107), calicheamicin (US Patent Publication No. 2009 / 0105461, Cancer Res. 1993, 53, 3336-3342), meltansine, daunomycin, doxorubicin, methotrexate, vindesine, SG2285 (Cancer Res.2010,70(17),6849-6858), drastatin, drastatin analog auristatin (U.S. Patent No. 5,635,483), cryptophycin, camptothecin, camptothecin analogs (e.g., SN38, FL118, or exatecan), rhizoxin derivatives, CC1065 analogs or derivatives, duocalmycin, engine antibiotics, esperamicin, epotilon, pyrrolobenzodiazepine (PBD) derivatives The material may be any one selected from, but is not limited to, the following: α-amanitin, toxoids, Toll-like receptor 5 (TLR5) agonists, Toll-like receptor 7 (TLR7) agonists, Toll-like receptor 8 (TLR8) agonists, 1,4,7-triazacyclononane-1,4,7-triacetate (NOTA), and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA), or analogs thereof.

[0111] In this application, when referring to the numbering of amino acid residues in the Fc domain (or Fc region) of an antibody, the numbering of amino acid residues follows the EU numbering system unless otherwise specified. Since the IgG sequence was investigated, as described in Edelman GM, et al., The covalent structure of an entire gamma-G immunoglobulin molecule, Proc Natl Acad Sci USA., 1969 May;63(1):78-85, the EU numbering system has been widely used as a sequencing system for the Fc region. For example, at lysine 246 in the Fc region, the number 246 is a number assigned according to the EU numbering system. As another example, at lysine 248 in the Fc region, the number 248 is a number assigned according to the EU numbering system.

[0112] As used herein, the terms “linked” or “connected” mean that two or more elements present in a conceptualizable structure are directly or indirectly linked (e.g., by other elements such as linkers), and are not intended to mean that no other additional elements can exist between the two or more elements. For example, a description such as “element B linked to element A” is intended to include both cases where one or more other elements are present between elements A and B (i.e., element A is linked to element B by one or more other elements) and cases where one or more other elements are not present between elements A and B (i.e., elements A and B are directly linked), and is not intended to be interpreted restrictively.

[0113] As used herein, the term “sequence identity” is a term used in relation to the degree of similarity between two or more sequences. For example, the term “sequence identity” is used in conjunction with terms referring to a reference sequence and terms expressing a percentage. For example, the term “sequence identity” may be used to describe a sequence that is similar to or substantially identical to a reference amino acid sequence. When a description such as “a sequence having 90% or more sequence identity with sequence A” is used, the reference sequence is sequence A in this specification. For example, the percentage of sequence identity may be calculated by aligning the reference sequence and the sequence being measured with respect to the percentage of sequence identity. The method for calculating and / or determining the percentage of sequence identity is not particularly limited and may be calculated and / or determined by any reasonable method or algorithm that can be used by those skilled in the art.

[0114] As used herein, in some embodiments, “unit” is used to distinguish a substance conjugated from a free substance. The term “unit” as used in some embodiments is illustrated by illustrating antibody units and free antibodies. Free antibody refers to an antibody molecule that is not covalently bonded to another molecule or group. Antibody unit refers to a group derived from the free antibody that is covalently bonded to another molecule or group. For example, an antibody-functional group conjugate can be prepared when a free antibody and a functional substance are combined by the reaction of the reactive group of the functional group with the primary amine group of a lysine residue of the free antibody. In this case, the portion derived from the free antibody may be called an antibody unit. In an antibody-functional group conjugate, the antibody unit may be understood to be structurally identical to the free antibody from which the antibody unit originates, except for the portion that is conjugated with the non-antibody portion of the antibody-functional group conjugate. For example, if the primary amine group of the lysine residue involved in the reaction in the free antibody is illustrated separately, the structure of the free antibody is: [ka] It can be expressed as ". When the junction between the antibody unit and parts other than the antibody unit is illustrated separately in an antibody unit, the structure of the antibody unit is " [ka] It can be expressed as follows: Therefore, the antibody unit and the free antibody can be understood to be structurally identical except for the primary amine group of the lysine residue used in the reaction. Therefore, in some embodiments, the antibody unit and the free antibody cannot be distinguished separately and may be called the “antibody,” and these terms may be interpreted as appropriate depending on the context. In some embodiments, when a statement such as “the antibody unit is derived from the antibody” is used, the antibody unit and the antibody can be understood to have the relationship described above. In some embodiments, when a statement such as “the Fc-binding unit is derived from the Fc-binding substance” is used, the “Fc-binding unit and the Fc-binding substance” can be understood to have a similar relationship described above. That is, the Fc-binding unit can be understood to have the same structure as the Fc-binding substance from which it originates, except for the junction to which the Fc-binding unit is attached to a part other than the Fc-binding unit. Similar to the antibody unit, in some embodiments, the Fc-binding unit may be called the Fc-binding substance from which it originates, and these terms may be interpreted as appropriate depending on the context.

[0115] When descriptions such as "A includes B" are used in this specification, they should be interpreted as not excluding the possibility that A includes additional components other than B. That is, "A includes B" is intended to encompass cases where additional elements other than B exist within A (for example, cases where B and C exist within A), cases where A is B, and cases where A consists of B. On the other hand, since "A includes B" encompasses all of the above cases, it may be used in conjunction with "A is B," "A consists of B," or "A is represented by B." The fact that the description "A includes B" may be used in conjunction with "A is B" means that the description "A is B" may be newly created from the description "A includes B" already existing in this specification, and does not mean that the description "A includes B" should be interpreted restrictively as "A is B." When descriptions such as "A includes B" are used, it should be interpreted that additional elements other than B may exist within A. In other words, when a description such as "A includes B" is used in this specification, it should be interpreted as encompassing both cases where A is B, and cases where A contains additional elements in addition to B.

[0116] When descriptions such as "A has B" are used in this specification, they should be interpreted as not excluding the possibility that A has additional components other than B. That is, "A has B" is intended to encompass cases where additional elements other than B exist within A (for example, cases where B and C exist within A), cases where A is B, and cases where A consists of B. On the other hand, since "A has B" encompasses all of the above cases, it may be used in conjunction with "A is B," "A consists of B," or "A is represented by B." The fact that the description "A has B" may be used in conjunction with "A is B" means that the description "A is B" may be newly created from the description "A has B" that already exists in this specification, and does not mean that the description "A has B" should be interpreted restrictively as "A is B." When descriptions such as "A has B" are used, it should be interpreted that additional elements other than B may exist within A. In other words, when descriptions such as "A has B" are used in this specification, they should be interpreted as encompassing both cases where A is B, and cases where additional elements exist within A in addition to B.

[0117] Where compounds (e.g., small compounds, peptides, antibodies, and conjugates) are disclosed herein, it should be understood that their salt forms are also disclosed. Examples of ions that form salts of compounds include ammonium, calcium, sodium, potassium, and acetic acid (CH3COO). - ), carbon dioxide (CO3 2- ), chloride (Cl - ), citric acid, cyanide, fluoride (F - ), nitric acid (NO3 - ), nitrite (NO2 - ), phosphoric acid (PO3 - ), and sulfuric acid (SO4 2-This includes, but is not limited to, salt-forming ions commonly used in the art, if necessary. The salt may be, for example, a pharmaceutically acceptable salt, which means a salt that has the potency of the parent and is not biologically undesirable (e.g., less toxic or non-toxic). Preferred salts include, for example, salts that can be formed by mixing a solution of the parent with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, phosphoric acid, sulfuric acid, or acetic acid. For example, if the compound contains an acidic residue, the pharmaceutically acceptable salt may include salts formed using suitable organic ligands such as alkali metal ions (sodium or potassium), alkaline earth metal ions (calcium or magnesium), and ammonium ions.

[0118] Hereafter, for better understanding, antibody structures will be specifically described based on what is generally known in the art, and the scope of this application is not limited by the following description.

[0119] The structure of an antibody can be divided into a heavy chain region and a light chain region depending on the type of chain. The structure of an antibody can be divided into a fragment antigen-binding region (Fab region) and a fragment crystallizable region (Fc region) according to its antigen-binding function. The structure of an antibody can be divided into a variable region and a constant region according to the variability of its amino acid sequence. Other parts of the antibody structure include a hinge region and a tail region. The heavy chain region and light chain region can be described as functionally divided into a fragment antigen-binding region (Fab region) and a fragment crystallizable region (Fc region). The Fab region is a portion containing a part that binds to the antigen (antigen-binding site). The Fc region is a portion capable of binding to the fc receptor. The heavy chain region can be described as having both a Fab region and an Fc region, and the light chain region can be described as having a Fab region.

[0120] The Fab region of the heavy chain includes the variable heavy chain region (VH) and the constant heavy chain region 1 (CH1). For example, in IgG1, the Fc region is known to include the constant heavy chain region 2 (CH2) and the constant heavy chain region 3 (CH3). In this case, the entire constant heavy chain region of the antibody can be called CH. For example, the entire region combining CH1, CH2, and CH3 of IgG1 can be represented as CH.

[0121] The Fab region of the light chain includes the variable light chain region (VL) and the constant light chain region (CL). The light chain region can be described as lacking an Fc region.

[0122] The aforementioned VH, CH1, CH2, CH3, VL, and CL can each be called immunoglobulin domains.

[0123] The immunoglobulin domains in the heavy chain region are known to be located in the order of VH, CH1, CH2, and CH3 or VH, CH1, CH2, CH3, and CH4, from the N-terminus to the C-terminus. The immunoglobulin domains in the light chain region are known to be located in the order of VL and CL, from the N-terminus to the C-terminus. In general, the heavy chain region and the light chain region are linked by disulfide bonds, and the Fab region and the Fc region are linked by hinges. Specifically, the C-terminus of CH1 and the N-terminus of CH2 in the heavy chain region are known to be linked by hinges.

[0124] The variable regions (VH and VL) are regions containing the antigen-binding site. Within the variable regions, there is a portion with the greatest variability (hypervariable region), and the corresponding portion is called the complementarity-determining region (CDR). VH contains three CDRs, which are generally referred to as CDRH1, CDRH2, or CDRH3. The CDRs in VH can be understood to be located in the order CDRH1, CDRH2, and CDRH3 from the N-terminus to the C-terminus. VL also contains three CDRs, which are generally referred to as CDRL1, CDRL2, or CDRL3. The CDRs in VH can be understood to be located in the order CDRL1, CDRL2, and CDRL3 from the N-terminus to the C-terminus.

[0125] The constant region of an antibody is a region distinct from the antigen-binding region, and it is known that the constant region can interact with cells or molecules of the immune system. For example, the constant region can interact with (bind to or ligate to) the cell membrane of immune cells (e.g., lymphocytes, neutrophils, dendritic cells, and / or macrophages). Specifically, the hinge region and / or the CH2 portion of the constant region can bind to receptors on the cell membrane of immune cells (e.g., FcεRIII). In another embodiment, the constant region can bind to FcRn.

[0126] The constant regions of the heavy chain domains mentioned above (hereinafter referred to as "heavy chain constant regions") can be broadly divided into five types (classes or isotypes): alpha (α), gamma (γ), delta (δ), epsilon (ε), and mu (μ). In this case, the type of heavy chain constant region mentioned above is not determined individually for CH1, CH2, CH3, and CH4, but is determined by considering all heavy chain constant regions contained in the antibody (CH1, CH2, and CH3; or CH1, CH2, CH3, and CH4).

[0127] There are two types of steady-state regions in the light chain (hereinafter referred to as the "light chain steady-state region"), and these two types are lambda (λ) and kappa (κ).

[0128] Antibody types are known to be broadly classified into five types (classes or isotypes). These five types are determined by the type of heavy chain constant region.

[0129] The five antibody types mentioned above are immunoglobulin M (IgM), immunoglobulin D (IgD), immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin A (IgA), and immunoglobulin E (IgE). If the type of the constant region of the heavy chain of an antibody is classified as alpha, the antibody type may be recognized as IgA. If the type of the constant region of the heavy chain of an antibody is classified as gamma, the antibody type may be recognized as IgG. If the type of the constant region of the heavy chain of an antibody is classified as delta, the antibody type may be recognized as IgD. If the type of the constant region of the heavy chain of an antibody is classified as epsilon, the antibody type may be recognized as IgE. If the type of the constant region of the heavy chain of an antibody is classified as mu, the antibody type may be recognized as IgM. For example, each heavy chain of IgG is known to contain four immunoglobulin domains (VH, CH1, CH2, and CH3).

[0130] Among the five antibody types, IgG and IgA are known to be further classified into more detailed subclasses. For example, when describing an antibody that is a human antibody, if the type of the heavy chain constant region of the antibody is gamma 1 (γ1), the antibody type is IgG1; if the type of the heavy chain constant region of the antibody is gamma 2 (γ2), the antibody type is IgG2; if the type of the heavy chain constant region of the antibody is gamma 3 (γ3), the antibody type is IgG3; and if the type of the heavy chain constant region of the antibody is gamma 4 (γ4), the antibody type is IgG4. If the heavy chain constant region of a human antibody is alpha 1 (α1), the antibody type is IgA1; and if the heavy chain constant region of a human antibody is alpha 2 (α2), the antibody type is IgA2.

[0131] Compounds containing Fc-bonding units provided in some embodiments of the present application will be described in detail thereafter.

[0132] Compounds containing Fc binding units Related technologies and related technologies As mentioned above, research has been conducted on compounds containing Fc-binding units for site-specific transfer of substances of interest (e.g., bioorthogonal functional groups) to antibodies. The literature [Korean Patent Application No. 10-2020-0091826 (Application No. 10-2020-0009162)] discloses a compound having the structure of formula 1-1 as a compound containing an Fc-binding unit. [Formula 1-1] [ka] .

[0133] In the compound of formula 1-1, the Fc-binding unit (FcBU) induces a compound containing the Fc-binding unit near lysine residues 246 and 248 located in the Fc region of the antibody. The carbonyl group directly linked to the norbornene group, which is a bioorthothic functional group, reacts with the amino group of lysine residue 246 (K246) or lysine residue 248 (K248) of the antibody. Through this reaction, the Fc-binding unit is released, and the norbornene group is moved to lysine residue 246 or lysine residue 248 in the Fc region of the antibody. In the compound of formula 1-1, the structure [ka] (In this case, in the structure, * represents the carbonyl group that reacts with the amino group of the antibody's lysine residue) allows a compound containing the Fc binding unit to react with the antibody under physiological conditions (e.g., pH 7.4), and allows the norbornene group to move to a desired position (e.g., K246 or K248). On the one hand, NHS esters are used as the group that reacts with the antibody in some cases, but when an N-hydroxysuccinimide (NHS ester) group is used, the reaction conditions need to be adjusted to acidic conditions. When acidic conditions are used as reaction conditions, additional substances or additional processes are required to adjust the pH, and furthermore, acidic conditions can affect the structure of the antibody, resulting in disadvantages to reactions under acidic conditions.

[0134] On the other hand, the inventors of the present application have confirmed that there is a problem with the reaction efficiency (i.e., reaction efficiency with antibodies) of the compound of formula 1-1 disclosed in the prior art [Republic of Korea Patent Application No. 10-2020-0091826 (Application No. 10-2020-0009162)].

[0135] Development of compounds containing novel Fc-binding units As described above, the inventors of this application have confirmed that there are problems with the reaction efficiency of the compound of formula 1-1 disclosed in the prior art. The results of an investigation into the reaction between the compound of formula 1-1 and the antibody are disclosed in Example 02. As disclosed in Example 02, the compound of formula 1-1 showed low reaction efficiency in its reaction with the antibody.

[0136] To improve the low reaction efficiency of the compound of formula 1-1, the inventors of the present application initially intended to develop the compound of formula 1-2, which is a compound in which the norbornene group is changed from a chemical formula 1-1 to an azide group. However, the compound of formula 1-2 was found to be extremely unstable. Accordingly, the inventors of the present application identified that the compound of formula 1-2 cannot be used to transfer the substance of interest to an antibody. [Formula 1-2] [ka] .

[0137] To improve the low reaction efficiency of the compound of formula 1-1, the inventors of the present application then designed a novel compound containing a peptide linker (Val-Gly or Ala-Gly) between the azide and carbonyl groups. The newly designed compounds with the added peptide linker have the structures of formulas 1-3 and 1-4. The inventors of the present application prepared compounds having the structures of formulas 1-3 and 1-4 and performed conjugate experiments with these compounds and antibodies. However, as described in Examples 03 and 04, the compounds containing the peptide linker between the azide and carbonyl groups reacted irregularly with the antibody. Therefore, the inventors of the present application found it difficult to use the compounds of formulas 1-3 and 1-4 to transfer the substance of interest to the antibody. Formula 1-3 below is the compound with the Val-Gly peptide linker introduced. Formula 1-4 below is the compound with the Ala-Gly peptide linker introduced. [Formula 1-3] [ka] , [Formula 1-4] [ka] .

[0138] As described above, the inventors of this application attempted various structural modifications to improve the low reaction efficiency of compounds containing Fc-bonding units in related technologies, but were unable to easily find compounds containing Fc-bonding units suitable for the reaction. Furthermore, because the possible positions for structural modifications are diverse, the resulting structures are also diverse, making it difficult to develop novel compounds containing Fc-bonding units with improved reaction efficiency. However, after considerable effort, the inventors of this application finally succeeded in developing a novel compound containing Fc-bonding units with improved reaction efficiency.

[0139] Compounds containing the Fc-bonding unit provided by this application will be described in detail thereafter.

[0140] Overview of compounds containing the Fc binding unit of this application Some embodiments of the present application provide compounds comprising an Fc-binding unit. Compounds comprising an Fc-binding unit may be called compounds for transferring a group of interest to an antibody. Compounds comprising an Fc-binding unit may be called compounds for site-specific transfer of a group of interest to an antibody.

[0141] Compounds containing Fc-binding units can be used to transfer a group of interest (e.g., a bioorthothic functional group) to an antibody.

[0142] Compounds containing Fc-binding units can be used to move a group of interest (e.g., a bioorthothic functional group) to the target region of an antibody.

[0143] Compounds containing an Fc binding unit can be used to move a group of interest (e.g., a bioorthothic functional group) to a site of interest on an antibody (e.g., K246 or K248 in the Fc region of the antibody).

[0144] Hereafter, the structures of compounds containing Fc-bonding units provided according to several embodiments of the present application will be described in detail.

[0145] Compounds containing an Fc-binding unit according to some embodiments of the present application may have the structure of formula 2.

[0146] Some embodiments of this application are given by formula 2: [ka] The present invention provides a compound having the structure described herein.

[0147] In Equation 2, D a This is spacer A.

[0148] In Equation 2, L a This is linker A.

[0149] In Equation 2, X is C, O, or N (i.e., -X- is -CH2-, -O-, or -NH-).

[0150] In Equation 2, GOI is a base of interest.

[0151] In Equation 2, FcBU is an Fc coupling unit.

[0152] In Equation 2, R a1 is H or C 1~6 It is alkyl.

[0153] In Equation 2, R a2 is H or C 1~6 It is alkyl.

[0154] In Equation 2, R a3 is H or C 1~6 It is alkyl.

[0155] In Equation 2, J a These are -C(=O)-, -S-, -NH-, or -C(=NH)-.

[0156] The elements of each compound in Equation 2 will be explained in detail below.

[0157] Spacer A (D"a) In Equation 2, D a This is spacer A. In the entry "Spacer A (D"a)", the "a" in D"a represents the superscript letter a. That is, D"a is D a This is how it is understood.

[0158] In some embodiments, spacer A is bonded to, replaced by, or not replaced by C 1~20 Alkylene, substituted or unsubstituted C 1~20 Heteroalkylenes, substituted or unsubstituted C 2~20 Alkenylene, substituted or unsubstituted C 2~20 Heteroalkenylenes, substituted or unsubstituted C 2~20Alkynylene, or substituted or unsubstituted C 2~20 It may also be a heteroalkylene. Here, "substituted" means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more types of substituents. That is, a substituted alkylene may contain one or more types of substituents. For example, each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is independently H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The heteroalkylene, heteroalkene, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH may be selected. In this, the heteroalkylene, heteroalkenylene, heteroalkynylene, heterocycloalkyl, and heteroaryl each independently contain one or more heteroatoms, and each heteroatom may independently be selected from N, O, and S.

[0159] In a particular embodiment, spacer A is not replaced by C 1~20 Alkylene, unsubstituted C 1~20 heteroalkylene, unsubstituted C 2~20 Alkenylene, unsubstituted C 2~20 heteroalkenylene, unsubstituted C 2~20 Alkynylene or unsubstituted C 2~20 It may also be a heteroalkylene. In this, each of the heteroalkylene, heteroalkenylene, and heteroalkylene independently contains one or more heteroatoms, and each of the heteroatoms may independently be selected from N, O, and S.

[0160] In a particular embodiment, spacer A is not replaced by C 1~10 Alkylene, unsubstituted C 1~10heteroalkylene, unsubstituted C 2~10 Alkenylene, unsubstituted C 2~10 heteroalkenylene, unsubstituted C 2~10 Alkynylene or unsubstituted C 2~10 It may also be a heteroalkylene. In this, each of the heteroalkylene, heteroalkenylene, and heteroalkylene independently contains one or more heteroatoms, and each of the heteroatoms may independently be selected from N, O, and S.

[0161] In a particular embodiment, spacer A is not replaced by C 1~6 Alkylene or unsubstituted carbon 1~6 It may be a heteroalkylene, in which the heteroalkylene comprises one or more heteroatoms, each of which heteroatoms may be independently selected from N, O, or S. In certain embodiments, each heteroatom may be O.

[0162] In certain embodiments, spacer A may be an unsubstituted C3 alkylene or an unsubstituted C3 heteroalkylene, where the heteroalkylene comprises one or more heteroatoms, each of which may be independently selected from N, O, or S. In certain embodiments, each of the heteroatoms may be O.

[0163] In a particular embodiment, spacer A is not replaced by C 1~6 Alkylene is also acceptable.

[0164] In certain embodiments, spacer A may be an unsubstituted C3 alkylene.

[0165] In some embodiments, spacers may be designed to adjust the distance between groups in a molecule. For example, spacer A may be designed to adjust the distance between two adjacent carbonyl groups. For example, the length of spacer A may be 0 to 20 based on the number of atoms in the main chain (i.e., the number of atoms located in the main chain) (if the number of atoms in the main chain is 0, spacer A is a bond). For example, spacer A may include a ring group in the main chain, in which case the number of atoms in the main chain may, for convenience, be counted based on two atoms that form a bond with other acyclic parts on the ring, in which case the number may be counted in the direction of achieving the smallest possible number. For example, [ka] If the ring is present in the main chain of spacer A, the number of atoms in the main chain counted by the ring is 3. For example, [ka] If the ring is present in the main chain of spacer A, the number of atoms in the main chain counted by the ring is 5.

[0166] Linker A(L"a) In Equation 2, L a This is linker A.

[0167] In some embodiments, the length of linker A may be between 0 and 100, based on the number of atoms in the main chain. For example, linker A may contain ring groups in the main chain.

[0168] In some embodiments, linker A is linked, substituted, or unsubstituted C 1~100 Alkylene, substituted or unsubstituted C 1~100 Heteroalkylenes, substituted or unsubstituted C 2~100 Alkenylene, substituted or unsubstituted C 2~100 Heteroalkenylenes, substituted or unsubstituted C 2~100Alkynylene, or substituted or unsubstituted C 2~100 It may also be a heteroalkylene. Here, "substituted" means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more types of substituents. That is, a substituted alkylene, etc., may contain one or more types of substituents. For example, each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH may be independently selected. In this, the heteroalkylene, heteroalkenylene, heteroalkylnylene, heterocycloalkyl, and heteroaryl each independently contain one or more heteroatoms, and each heteroatom may independently be selected from N, O, and S.

[0169] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene, unsubstituted C 1~60 heteroalkylene, unsubstituted C 2~60 Alkenylene, unsubstituted C 2~60 heteroalkenylene, unsubstituted C 2~60 Alkynylene or unsubstituted C 2~60 It may also be a heteroalkylene. In this, each of the heteroalkylene, heteroalkenylene, and heteroalkylene independently contains one or more heteroatoms, and each of the heteroatoms may independently be selected from N, O, and S.

[0170] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene, unsubstituted C 1~30heteroalkylene, unsubstituted C 2~30 Alkenylene, unsubstituted C 2~30 heteroalkenylene, unsubstituted C 2~30 Alkynylene or unsubstituted C 2~30 It may also be a heteroalkylene. Herein, each of the heteroalkylene, heteroalkenylene, and heteroalkylene independently contains one or more heteroatoms, each of which may be independently selected from N, O, and S. In certain embodiments, each of the heteroatoms may be O.

[0171] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene or unsubstituted carbon 1~30 It may also be a heteroalkylene. In this case, the heteroalkylene contains one or more heteroatoms, each of which may be independently selected from N, O, or S. In certain embodiments, each of the heteroatoms may be O.

[0172] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene or unsubstituted carbon 1~30 It may be a heteroalkylene. In this, the heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, each of the heteroatoms may be O. In this case, linker A is not substituted C. 1~30 In the case of a heteroalkylene, linker A is an unsubstituted C containing 0 to 10 ethylene glycol units. 1~30 Heteroalkylenes are also acceptable.

[0173] The ethylene glycol unit can be represented by -[EG]-, where -[EG]- is -[CH2OCH2]-, -[OCH2CH2]-, or -[CH2CH2O]-.

[0174] In a particular embodiment, linker A is bonded to, unsubstituted C 1~25 Alkylene or unsubstituted carbon 1~25 It may be a heteroalkylene. In this, the heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, each of the heteroatoms may be O. In this case, linker A is not substituted C. 1~25 If it is a heteroalkylene, linker A is an unsubstituted C containing 0 to 8 ethylene glycol units. 1~25 Heteroalkylenes are also acceptable.

[0175] In a particular embodiment, linker A is bonded to, unsubstituted C 1~20 Alkylene or unsubstituted carbon 1~20 It may be a heteroalkylene. In this, the heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, each of the heteroatoms may be O. In this case, linker A is not substituted C. 1~20 If it is a heteroalkylene, linker A is an unsubstituted C containing 0 to 6 ethylene glycol units. 1~20 Heteroalkylenes are also acceptable.

[0176] In a particular embodiment, linker A is bonded to, unsubstituted C 1~10 Alkylene or unsubstituted carbon 1~10 It may be a heteroalkylene. In this, the heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, each of the heteroatoms may be O. In this case, linker A is not substituted C. 1~10 If it is a heteroalkylene, linker A is an unsubstituted C containing 0 to 3 ethylene glycol units. 1~10 Heteroalkylenes are also acceptable.

[0177] In a particular embodiment, linker A is bonded to, unsubstituted C 1~5 Alkylene or unsubstituted carbon 1~5 It may be a heteroalkylene. In this, the heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, each of the heteroatoms may be O. In this case, linker A is not substituted C. 1~5 In the case of a heteroalkylene, linker A is an unsubstituted C containing 0 to 1 ethylene glycol unit. 1~5 Heteroalkylenes are also acceptable.

[0178] In some embodiments, linker A has the following structure: -L a1 -L a2 -L a3 - may have

[0179] At this point, L a1 It may be connected to X in Equation 2. In this case, L a3 This may be linked to the group of interest (GOI) of the object of interest in Equation 2.

[0180] In some embodiments, L a1 is a combined, or substituted or unsubstituted C 1~10 Alkylene, substituted or unsubstituted C 1~10 Heteroalkylenes, substituted or unsubstituted C 2~10 Alkenylene, substituted or unsubstituted C 2~10 Heteroalkenylenes, substituted or unsubstituted C 2~10 Alkynylene, or substituted or unsubstituted C 2~10It may also be a heteroalkylene. Here, "substituted" means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more types of substituents. That is, a substituted alkylene, etc., may contain one or more types of substituents. For example, each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH may be independently selected. In this, the heteroalkylene, heteroalkenylene, heteroalkylnylene, heterocycloalkyl, and heteroaryl each independently contain one or more heteroatoms, and each heteroatom may independently be selected from N, O, and S.

[0181] In some embodiments, L a2 is a combination, or -[EG] x -This may also be the case. In this, x may be an integer from 1 to 20. In this, -[EG]- is an ethylene glycol unit, which is -[CH2OCH2]-, -[OCH2CH2]-, or -[CH2CH2O]-. -[EG] x - is -[CH2OCH2] 1~20 -,-[OCH2CH2] 1~20 -, or -[CH2CH2O] 1~20 - can be expressed as L a2 This may be a bond, or it may consist of 1 to 20 ethylene glycol units.

[0182] In some embodiments, L a3 is a combined, or substituted or unsubstituted C 1~10 Alkylene, substituted or unsubstituted C 1~10Heteroalkylenes, substituted or unsubstituted C 2~10 Alkenylene, substituted or unsubstituted C 2~10 Heteroalkenylenes, substituted or unsubstituted C 2~10 Alkynylene, or substituted or unsubstituted C 2~10 It may also be a heteroalkylene. Here, "substituted" means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more types of substituents. That is, a substituted alkylene, etc., may contain one or more types of substituents. For example, each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH may be independently selected. In this, the heteroalkylene, heteroalkenylene, heteroalkylnylene, heterocycloalkyl, and heteroaryl each independently contain one or more heteroatoms, and each heteroatom may independently be selected from N, O, and S.

[0183] In a particular embodiment, L a1 This is a C that is not bonded or substituted. 1~3 Alkylene or unsubstituted carbon 1~3 It may also be a heteroalkylene. In this case, the heteroalkylene comprises one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, the heteroalkylene comprises one or more heteroatoms, each of which may be O.

[0184] In a particular embodiment, L a2 is a combination or -[EG] x- may also be an integer between 1 and 10. In a particular embodiment, x may be an integer between 1 and 7. In a particular embodiment, x may be an integer between 1 and 5. In a particular embodiment, x may be an integer between 1 and 3.

[0185] In a particular embodiment, L a3 This is a C that is not bonded or substituted. 1~3 Alkylene or unsubstituted carbon 1~3 It may also be a heteroalkylene. In this case, the heteroalkylene comprises one or more heteroatoms, each of which may be independently selected from N, O, and S. In a particular embodiment, the heteroalkylene comprises one or more heteroatoms, each of which may be O.

[0186] In some embodiments, linker A has the following structure: [ka] and [ka] It may have any one of the following: During the ceremony, se is an integer between 0 and 15. sb is an integer between 0 and 3. sc is an integer between 1 and 15. sd is an integer between 0 and 3.

[0187] In some embodiments, linker A has the following structure: [ka] It may have, During the ceremony, sf is an integer between 0 and 8. sg is an integer between 0 and 15. sh is an integer between 0 and 8.

[0188] In certain embodiments, sf may be an integer between 0 and 6. In certain embodiments, sf may be an integer between 0 and 3. In certain embodiments, sg may be an integer between 0 and 10. In certain embodiments, sg may be an integer between 0 and 7. In certain embodiments, sh may be an integer between 0 and 6. In certain embodiments, sh may be an integer between 0 and 3.

[0189] In some embodiments, X(L) of Equation 2 a If X) connected to is O, then the sum of sf, sg, and sh does not have to be zero (i.e., at least one of sf, sg, and sh is an integer greater than 1).

[0190] In some embodiments, linker A has the following structure: [ka] [ka] [ka] and [ka] It may have any one selected from the following.

[0191] In some embodiments, it may be preferable that linker A is designed to be slightly reactive or non-reactive. That is, it may be preferable that linker A is designed in an unsubstituted form, or that linker A contains substituents that are slightly reactive or non-reactive, even if it contains substituents.

[0192] As will be described later, the reaction of an antibody with a compound containing an Fc binding unit involves the carbonyl group (structure ") of the compound containing the Fc binding unit. [ka] This can be specifically described as a reaction between the carbonyl group marked with an asterisk (*) and the amino group of lysine residue 246 or 248 of the antibody (i.e., the primary amine group of the lysine side chain). On the one hand, the Fc-binding unit contained in the compound containing the Fc-binding unit guides the compound to the Fc region of the antibody, bringing the carbonyl group marked with an asterisk (*) and the amino group of lysine residue 246 or 248 of the antibody closer together. That is, the Fc-binding unit guides the carbonyl group marked with an asterisk (*) to react with the amino group of lysine residue 246 or 248 of the antibody. Therefore, the length of linker A, rather than the structure between the Fc-binding unit and the carbonyl group marked with an asterisk (*), can be designed more freely than other structures of the compound containing the Fc-binding unit. Furthermore, the inventors of the present invention conducted experiments with various lengths of linker A and confirmed that even when the length of linker A is changed, the compound containing the Fc binding unit exhibits excellent reaction efficiency in reaction with antibodies (see Examples 07 and 08).

[0193] R"a1 As described above, in Equation 2, R a1 H or C 1~6 It may be alkyl. In some embodiments, R a1 H or C 1~4 Alkyl is also acceptable. In this case, C 1~4 Alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl. In certain embodiments, R a1 H or C 1~3 It may also be alkyl. In certain embodiments, R a1 H or C 1~2 It may also be alkyl. In certain embodiments, R a1 It may also be methyl.

[0194] R"a2 and R"a3 As described above, in Equation 2, Ra2 H or C 1~6 It may be alkyl. In some embodiments, R a2 H or C 1~4 Alkyl is also acceptable. In this case, C 1~4 Alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl. In certain embodiments, R a2 H or C 1~3 It may also be alkyl. In certain embodiments, R a2 H or C 1~2 It may also be alkyl. In certain embodiments, R a2 R may be H or methyl. In certain embodiments, R a2 H may also be used.

[0195] As described above, in Equation 2, R a3 H or C 1~6 It may be alkyl. In some embodiments, R a3 H or C 1~4 Alkyl is also acceptable. In this case, C 1~4 Alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl. In certain embodiments, R a3 H or C 1~3 It may also be alkyl. In certain embodiments, R a3 H or C 1~2 It may also be alkyl. In certain embodiments, R a3 R may be H or methyl. In certain embodiments, R a3 H may also be used.

[0196] In a particular embodiment, R a2 If it is not H, then R a3 It may be H. In certain embodiments, R a3 If it is not H, then R a2 It may be H. In certain embodiments, R a2 and Ra3 Both can be H.

[0197] X As stated above, X may be C, O, or N (i.e., X is -CH2-, -O-, or -NH-). In some embodiments, X may be C or O. In certain embodiments, X may be C. In certain embodiments, X may be O.

[0198] J"a As mentioned above, in Equation 2, J a is -C(=O)-, -S-, -NH-, or -C(=NH)-. In Equation 2, J a This represents the joint substructure of FcBU and other parts that are not FcBU. a This may be called, for example, a conjugate substructure A or a joint substructure A. In a particular embodiment, J a It can also be -C(=O)-.

[0199] Group of Interest (GOI) Overview of the subject of interest In Equation 2, GOI is the group of interest. In some embodiments, the group of interest may include a reactive group. The group of interest may include one or more reactive groups. In some embodiments, the group of interest may include a functional group. The group of interest may include one or more functional groups. The group of interest may include one or more reactive groups and one or more functional groups. For example, the group of interest may include one or two or more reactive groups. For example, the group of interest may include one or two or more functional groups. For example, the group of interest may include one reactive group and one functional group. For example, the group of interest may include one reactive group and two or more functional groups. For example, the group of interest may include two or more reactive groups and one functional group. For example, the group of interest may include two or more reactive groups and two or more functional groups. If the group of interest includes multiple reactive groups, each of the reactive groups is selected independently. If the group of interest includes multiple functional groups, each functional group is selected independently. In some embodiments, the group of interest may be a reactive group or a functional group. In certain embodiments, the group of interest may be a reactive group. For example, the group of interest may be a group intended to transfer to an antibody.

[0200] In some embodiments, the sum of the atomic masses of all atoms constituting the group of interest may be 5,000 doltons or less, 4,000 doltons or less, 3,000 doltons or less, 2,000 doltons or less, 1,500 doltons or less, 1,000 doltons or less, 900 doltons or less, 800 doltons or less, 700 doltons or less, 600 doltons or less, 500 doltons or less, 400 doltons or less, 300 doltons or less, or 100 doltons or less.

[0201] The reactive groups and functional groups will be explained in detail below.

[0202] Reactive group (RG) The group of interest may include a reactive group.

[0203] In some embodiments, the group of interest may be a reactive group.

[0204] The reactive group may include a reactive substructure. The reactive substructure may refer to a substructure that is reactive with other molecules or groups in other molecules.

[0205] In some embodiments, the reactive substructure may be a click chemical functional group or a bioorthogonal functional group, but is not limited to these, and may be selected from any reactive group.

[0206] In some embodiments, the sum of the atomic masses of all atoms constituting the reactive group may be 3,000 doltons or less, 2,500 doltons or less, 2,000 doltons or less, 1,500 doltons or less, 1,000 doltons or less, 900 doltons or less, 800 doltons or less, 700 doltons or less, 600 doltons or less, 500 doltons or less, 400 doltons or less, 300 doltons or less, 200 doltons or less, or 100 doltons or less.

[0207] In some embodiments, the reactive group has the following structure: [ka] It may have. In the formula, D RG H is a spacer for the reactive group (spacer RG), RGThis is a reactive substructure. In some embodiments, the reactive substructure may be a click chemical functional group. In some embodiments, the reactive substructure may be a bioorthogonal functional group.

[0208] In some embodiments, spacer (D RG The length of the ) may be 0 to 6, based on the number of atoms in the main chain. In some embodiments, D RG is a combined, or substituted or unsubstituted C 1~6 Alkylene, substituted or unsubstituted C 1~6 Heteroalkylenes, substituted or unsubstituted C 2~6 Alkenylene, substituted or unsubstituted C 2~6 Heteroalkenylenes, substituted or unsubstituted C 2~6 Alkynylene, substituted or unsubstituted C 2~6 Heteroalkylene, substituted or unsubstituted C 3~8 Cycloalkylene, substituted or unsubstituted C 3~8 Heterocycloalkylenes, substituted or unsubstituted C 3~8 Cycloalkenylenes (e.g., aryl), or substituted or unsubstituted C 3~8 It may also be a heterocycloalkenylene (e.g., heteroaryl). Here, "substituted" means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more types of substituents. That is, a substituted alkylene, etc., may contain one or more types of substituents. For example, each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10The substituents may be independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, -COOH, =O, =S, and -SH. In certain embodiments, each substituent is -C 1~4 The heteroalkylene, -C(=O)H, -C(=O)CH3, -C(=O)OH, -C(=O)NH2, -NH2, =NH, =O, =S, -OH, -NO2, and -SH may be independently selected. In this, each of the heteroalkylene, heteroalkenylene, and heteroalkylynylene independently contains one or more heteroatoms, and each of the heteroatoms may independently be selected from N, O, and S.

[0209] In a particular embodiment, D RG is a combined, or substituted or unsubstituted C 1~6 Alkylene, substituted or unsubstituted C 1~6 It may also be a heteroalkylene. In this case, the substituted alkylene or substituted heteroalkylene may contain one or more types of substituents, each of which substituents is -C 1~4 Alkyl and =O may be selected independently. In this case, the heteroalkylene contains one or more heteroatoms, each of which may be independently selected from O, N, and S.

[0210] In a particular embodiment, D RG is a combined, or substituted or unsubstituted C 1~3 Alkylene, substituted or unsubstituted C 1~3 It may also be a heteroalkylene. In this case, the substituted alkylene or substituted heteroalkylene may contain one or more types of substituents, each of which substituents is -C 1~4 Alkyl and =O may be selected independently. In this case, the heteroalkylene contains one or more heteroatoms, each of which may be independently selected from O, N, and S.

[0211] In a particular embodiment, D RG They may be combined.

[0212] In a particular embodiment, the reactive group has the following structure: [ka] It may have.

[0213] Reactive substructure A reactive substructure may refer to a substructure that is reactive with other groups. A substance, molecule, or compound having a first reactive substructure (for example, a compound containing an Fc bond unit) can be conjugated with a substance, molecule, or compound having a second reactive substructure by a reaction between the reactive substructure and a substructure that can react with the first reactive substructure (where the reactive substructure may be called the first reactive substructure, and the substructure that can react with the first reactive substructure may be called the second reactive substructure). In this case, the substance, molecule, or compound having the first reactive substructure and the substance, molecule, or compound having the second reactive substructure can be conjugated by a covalent bond.

[0214] In some embodiments, the reactive substructure may be a bioorthogonal functional group. A bioorthogonal functional group refers to a chemical functional group that participates in bioorthogonal chemistry or bioorthogonal reactions and carries out bioorthogonal reactions. The bioorthogonal reaction may be, but is not limited to, copper-free azide-alkyne cycloadditions, including Staudinger ligation, copper-catalyzed azide-alkyne cycloaddition (CuAAC), strain-accelerated azide-alkyne cycloaddition (SPAAC), tetrazine ligation, tetrazole ligation, oxime ligation, or isocyanide click reactions.

[0215] The bioorthogonal functional group may be selected from, for example, azide groups, terminal alkyne groups, terminal alkene groups, cyclic alkyne (e.g., cyclooctin) groups, tetrazine groups, norbornene groups, cycloalkene (e.g., cyclooctene) groups, oxime groups, and isocyanide groups, and is not particularly limited thereto. Cyclooctin may be any one selected from cyclooctin (OCT), bicyclononine (BCN), dibenzocyclooctin (DBCO), aza-dibenzocyclooctin (DIBAC), dibenzocyclooctinol (DIBO), difluorinated cyclooctin (DIFO), biarylazacyclooctinone (BARAC), dimethoxyazacyclooctin (DIMAC), and difluorobenzocyclooctin (DIFBO), and is not particularly limited thereto. Cyclooctene may be any one selected from, for example, cis-cyclooctene groups and trans-cyclooctene groups. In some embodiments, the group exemplified as a bioorthogonal functional group may have one or more types of substituents. Each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is H, halogen, or C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The following may be independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH.

[0216] In some embodiments, the bioorthogonal functional group has the following structure: [ka] [ka] [ka] and [ka] It may have any one of the following structures.

[0217] In some embodiments, hn may be an integer from 1 to 3, and each R H R may be H, or may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The following may be independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH. H If = O or = S, then two R H However, it should be understood that this forms one =O or =S.

[0218] In some embodiments, the reactive substructure may be a click chemical functional group. A click chemical functional group refers to a group that participates in a click chemical reaction. The click chemical reaction may be any one selected from Huisgen 1,3-dipolar cycloaddition; Diels-Alder reaction; reverse electron-demanded Diels-Alder (IEDDA) reaction; nucleophilic addition to small, strained rings such as epoxides and aziridines; nucleophilic addition to activated carbonyl groups; and Staudinger ligation; and addition reactions to carbon-carbon double or triple bonds. In some embodiments, the click chemical functional group may be selected from Diels-Alder dienes, Diels-Alder dienophiles, IEDDA dienes, and IEDDA dienophiles.

[0219] In some embodiments, the reactive substructure may be selected from azide groups, terminal alkyne groups, cyclic alkyne (e.g., cyclooctin) groups, tetrazine groups, norbornene groups, cycloalkenes (e.g., cyclooctene) groups, tetrazole groups, triazine groups, oxime groups, and isocyanide groups, halogen groups, aldehyde groups, nitrone groups, hydroxyamine groups, nitrile groups, hydrazine groups, ketone groups, broncate groups, cyanobenzothiazole groups, allyl groups, phosphine groups, maleimide groups, disulfide groups, thioester groups, halocarbonyl groups, isonitrile groups, cydonone groups, selenium groups, thiol groups, and protected thiol groups.

[0220] Functional group (FG) The group of interest may include a functional group.

[0221] In some embodiments, the group of interest may be a functional group.

[0222] The functional group may include an active substructure. The active substructure may be, but is not limited to, a drug, an imaging substructure, a radioactive substructure, a protein with a specific function, a peptide with a specific function, an affinity substance (e.g., biotin, streptavidin, and aptamers), a stabilizer, a vitamin, a nucleic acid (e.g., DNA or RNA), or a PEG substructure. In some embodiments, the active substructure may be a drug substructure, an imaging substructure, a radioactive substructure, or an affinity substance.

[0223] In some embodiments, the functional group may have a molecular weight (i.e., the sum of the atomic masses of all atoms constituting the functional group) of 5,000 doltons or less, 4,000 doltons or less, 3,000 doltons or less, 2,500 doltons or less, 2,000 doltons or less, 1,500 doltons or less, or 1,000 doltons or less.

[0224] In some embodiments, the functional group has the following structure: [ka] It may have, In the formula, D FG is a functional group spacer (spacer FG), and AM is the active substructure. In some embodiments, the active substructure may be a drug (e.g., a toxin). In some embodiments, the active substructure may be a radioactive substructure. In some embodiments, the active substructure may be an imaging substructure.

[0225] In some embodiments, a spacer for the functional group (D FG The length of the ) may be 0 to 6, based on the number of atoms in the main chain. In some embodiments, D FG is a combined, or substituted or unsubstituted C 1~6 Alkylene, substituted or unsubstituted C 1~6 Heteroalkylenes, substituted or unsubstituted C 2~6 Alkenylene, substituted or unsubstituted C 2~6 Heteroalkenylenes, substituted or unsubstituted C 2~6 Alkynylene, substituted or unsubstituted C 2~6 Heteroalkylene, substituted or unsubstituted C 3~8 Cycloalkylene, substituted or unsubstituted C 3~8 Heterocycloalkylenes, substituted or unsubstituted C 3~8 Cycloalkenylenes (e.g., aryl), or substituted or unsubstituted C 3~8It may also be a heterocycloalkenylene (e.g., heteroaryl). Here, "substituted" means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more types of substituents. That is, a substituted alkylene, etc., may contain one or more types of substituents. For example, each substituent may be independently selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where each R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The substituents may be independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH. In certain embodiments, each substituent is -C 1~4 The heteroalkylene, heteroalkenylene, and heteroalkylynylene may be independently selected from alkyl, -C(=O)H, -C(=O)CH3, -C(=O)OH, -C(=O)NH2, -NH2, =O, =S, -OH, -NO2, and -SH. In this, each heteroalkylene, heteroalkenylene, and heteroalkylynylene independently contains one or more heteroatoms, and each heteroatom may be independently selected from N, O, and S.

[0226] In a particular embodiment, D FG is a combined, or substituted or unsubstituted C 1~3 Alkylene, substituted or unsubstituted C 1~3 It may also be a heteroalkylene. In this case, the substituted alkylene or substituted heteroalkylene may contain one or more types of substituents, each of which substituents is -C 1~4 Alkyl and =O may be selected independently. In this case, the heteroalkylene contains one or more heteroatoms, each of which may be independently selected from O, N, and S.

[0227] In a particular embodiment, D FG They may be combined.

[0228] In a particular embodiment, the functional group has the following structure: [ka] It may have.

[0229] In some embodiments, the active substructure may be a drug (e.g., a drug unit or a conjugated drug). Examples of drugs include auristatin (e.g., monomethyl auristatin E), eribulin, tubulisin, geldanamycin (Kerr et al., 1997, Bioconjugate Chem. 8(6):781-784), mytansinoid (EP1391213, ACR 2008, 41, 98-107), calicheamicin (US Patent Publication No. 2009 / 0105461, Cancer Res. 1993, 53, 3336-3342), meltansine, daunomycin, doxorubicin, methotrexate, vindesine, SG2285 (Cancer Res.2010,70(17),6849-6858), drastatin, drastatin analog auristatin (U.S. Patent No. 5,635,483), cryptophycin, camptothecin, camptothecin analogs (e.g., SN38, FL118, or exatecan), rhizoxin derivatives, CC1065 analogs or derivatives, duocalmycin, engine antibiotics, esperamicin, epotilon, pyrrolobenzodiazepine (PBD) derivatives The material may be any one selected from, but is not limited to, the following: α-amanitin, toxoids, Toll-like receptor 5 (TLR5) agonists, Toll-like receptor 7 (TLR7) agonists, Toll-like receptor 8 (TLR8) agonists, 1,4,7-triazacyclononane-1,4,7-triacetate (NOTA), and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA), and their analogues.

[0230] In some embodiments, the active substructure may include a radioactive substructure. The radioactive substructure may be a ligand (e.g., a chelating agent) designed to bind to a radioactive isotope. In some embodiments, the radioactive substructure may include a complex of a chelating agent and a radioactive isotope (e.g., a chelate compound).

[0231] Fc coupling unit (FcBU) Overview of Fc bonding unit As described above, in Equation 2, FcBU is an Fc-binding unit. The Fc-binding unit may be derived from an Fc-binding substance. The Fc-binding substance will be described in detail below.

[0232] Fc binding substance Overview of Fc-binding substances Fc-binding substances are substances that possess binding properties to the Fc region of an antibody and have been used as components of compounds for moving a group of interest (e.g., compounds containing an Fc-binding unit) to move the group of interest to a target site on the antibody. Techniques for introducing a substance of interest (e.g., bioorthothic functional groups and drugs) to a specific position on an antibody using Fc-binding substances and compounds containing them are described in detail in the literature [EP19818561.3, published EP3811978; PCT patent application PCT / KR2020 / 003282, published WO2020 / 184944; and Republic of Korea patent application 10-2020-0009162, published 10-2020-0091826], all of which are cited by reference in their entirety herein. If necessary, Fc-binding substances may be called, but are not limited to, antibody-affinity substances, IgG-binding substances, site-specific antibody interactomes, and site-specific Fc interactomes.

[0233] Fc-binding material of the present invention Some embodiments of the present application provide an Fc-binding substance comprising an Fc-binding peptide having the amino acid sequence of SEQ ID NO: 01.

[0234] The amino acid sequence of sequence number 01 is as follows: (Xaa) 1-3 -C-(Xaa)2-H-Xa 1 -G-Xa 2 -LV-Xa 3 -C-(Xaa) 1-3 (Sequence ID: 01) As stated above, During the ceremony, Each of Xaa is independently selected from any amino acid, Xa 1 teeth [ka] In the formula, m is an integer from 1 to 10, and X f These are -NH2, -SH, or -C(=O)OH, Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues.

[0235] In some embodiments, in the amino acid sequence of SEQ ID NO: 01, the cysteine ​​residue adjacent to the N-terminus (i.e., the cysteine ​​residue located 2 to 4 amino acids from the N-terminus) and the cysteine ​​residue adjacent to the C-terminus (i.e., the cysteine ​​residue located 2 to 4 amino acids from the C-terminus) may optionally be covalently linked. For example, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be covalently linked by a disulfide bond. For example, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be a structure containing a carbonyl group. [ka] They may be connected by a covalent bond.

[0236] In some embodiments, each Xaa may independently be any amino acid other than cysteine.

[0237] In some embodiments, Xa 1 This may be a diaminopropionic acid (Dap) residue, a diaminobutyric acid (Dab) residue, an ornithine (Orn) residue, a lysine (Lys) residue, a 2,7-diaminoheptanoic acid residue, a 2,8-diaminooctanoic acid residue, a 2,9-diaminononanoic acid residue, a cysteine ​​residue, or a 2-aminosuberic acid residue.

[0238] For example, Xa 1 Structure [ka] In this case, m is 1, X f If Xa is -NH2, 1 This is a Dap residue. m is 2, and X f If Xa is -NH2, 1 This is a Dab residue. m is 3, and X f If Xa is -NH2, 1 This is an Orn residue. m is 4, and X f If Xa is -NH2, 1 This is a Lys residue. m is 5, and X f If Xa is -NH2, 1 is a 2,7-diaminoheptanoic acid residue. m is 1, and X f If it is -SH, then Xa 1 This is a Cys residue. m is 5, and X f If Xa is -COOH, 1 This is a 2-aminosuberic acid residue.

[0239] In some embodiments, Xa 1 Structure [ka] In this, m may be an integer from 1 to 5. In some embodiments, m may be an integer from 1 to 4.

[0240] Xa 1 Structure [ka] Structure Xa 1 It may be called, and is not particularly limited to, Xa 1 This may be called an amino acid residue having structure Xa1, and is not particularly limited thereto.

[0241] In a particular embodiment, Xa 1 The structure is as follows: [ka] It can be represented by, In this case, m may be an integer between 1 and 4.

[0242] In the structure, if m is 1, then Xa 1 This is a Dap residue. If m is 2, then Xa 1 This is a Dab residue. If m is 3, then Xa 1 This is an Orn residue. If m is 4, then Xa 1 This is a Lys residue.

[0243] Modifications typically used in the art may be made to the Fc-binding peptide (e.g., the amino acid sequence of SEQ ID NO: 01). In some embodiments, the Fc-binding peptide may have modifications that do not impair the intrinsic function of the Fc-binding peptide. For example, the Fc-binding peptide or Fc-binding substance may have a binding affinity to the Fc region of an antibody and may have modifications that do not impair this function. For example, the modifications may be for adjusting the stability or hydrophilicity of the Fc-binding peptide. For example, modifications may include the addition of a hydrophilic substructure, a hydrophobic substructure, a PEG substructure (e.g., PEGylation), an amide group (e.g., C-terminal amidation), a carbohydrate group, a hydroxyl group, a phosphate group, a prenyl group (e.g., prenylation), and / or a farnesyl group (e.g., farnesylation).

[0244] For example, the Fc-binding substance may further include one or more PEG substructures in addition to the Fc-binding peptide having the amino acid sequence of SEQ ID NO: 01. In this case, the PEG substructure may be covalently linked to the N-terminus and / or C-terminus of the Fc-binding peptide. For example, the Fc-binding substance may include an Fc-binding peptide and a PEG substructure, with the PEG substructure covalently linked to the C-terminus of the Fc-binding peptide. As another example, the Fc-binding substance may include an Fc-binding peptide and a PEG substructure, with the PEG substructure covalently linked to the N-terminus of the Fc-binding peptide. The PEG substructure may, for example, contain 1 to 30, 1 to 20, or 1 to 10 ethylene glycol units.

[0245] Hereafter, as an example, the structures of Fc-binding peptides with or without modifications added to the N-terminus and / or C-terminus of the amino acid sequence of SEQ ID NO: 01 are illustrated by formulas.

[0246] For example, the Fc-binding substance is given by the following equation 3: [Formula 3] (M F1 ) 0-1 -(Xaa) 1-3 -C-(Xaa)2-H-Xa1 -G-Xa 2 -LV-Xa 3 -C-(Xaa) 1-3 -(M F2 ) 0-1 It may have a structure, In the formula, M F1 and M F2 Each of these is an independent modification. Each of Xaa is independently any amino acid other than cysteine. Xa 1 teeth [ka] In the formula, m is an integer from 1 to 10, and X f These are -NH2, -SH, or -C(=O)OH, Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues.

[0247] In Equation 3, the cysteine ​​residues adjacent to the N-terminus (i.e., the cysteine ​​residues located 2nd to 4th from the N-terminus) and the cysteine ​​residues adjacent to the C-terminus (i.e., the cysteine ​​residues located 2nd to 4th from the C-terminus) may optionally be linked by covalent bonds. For example, the cysteine ​​residues adjacent to the N-terminus and the cysteine ​​residues adjacent to the C-terminus may optionally be linked by disulfide bonds.

[0248] In some embodiments, Xa 1 This may be a diaminopropionic acid residue, a diaminobutyric acid residue, an ornithine residue, a lysine residue, a 2,7-diaminoheptanoic acid residue, a 2,8-diaminooctanoic acid residue, a 2,9-diaminononanoic acid residue, a cysteine ​​residue, or a 2-aminosuberic acid residue.

[0249] As illustrated in Equation 3, M F1It may or may not exist.

[0250] As illustrated in Equation 3, M F2 It may or may not exist.

[0251] As described above, modifications may be selected from, for example, the addition of a hydrophilic substructure, a hydrophobic substructure, a PEG substructure (e.g., PEGylation), an amide group (e.g., C-terminal amidation), a carbohydrate group, a hydroxyl group, a phosphate group, a prenyl group (e.g., prenylation), and a farnesyl group (e.g., farnesylation).

[0252] In some embodiments, M F1 The group may be selected from a PEG substructure, an amide group, a carbohydrate group, a hydroxyl group, a phosphate group, a prenyl group, and a farnesyl group. In certain embodiments, M F1 This may be a PEG substructure.

[0253] In some embodiments, M F2 The group may be selected from a PEG substructure, an amide group, a carbohydrate group, a hydroxyl group, a phosphate group, a prenyl group, and a farnesyl group. In certain embodiments, M F2 It may also be an amide group.

[0254] In this case, the PEG substructure may contain 1 to 30, 1 to 20, or 1 to 10 ethylene glycol units (e.g., -CH2OCH2-, -OCH2CH2-, or -CH2CH2O-).

[0255] For example, the PEG substructure has the following structure: [ka] It may have.

[0256] In this case, D PEG This is a spacer in the PEG substructure.

[0257] For example, D PEG This may be a group having a main chain length of 0 to 6 (i.e., a group in which the total number of atoms located in the main chain is between 0 and 6).

[0258] For example, D PEG is a combined, or substituted or unsubstituted C 1~6 Alkylene, substituted or unsubstituted C 1~6 Heteroalkylenes, substituted or unsubstituted C 1~6 Alkenylene, substituted or unsubstituted C 1~6 A heteroalkenylene, a substituted or unsubstituted alkylene, or a substituted or unsubstituted heteroalkynylene, where a substituted alkylene, a substituted heteroalkynylene, a substituted alkenylene, or a substituted heteroalkynylene may contain one or more substituents, selected from -R, =O, =S, -NO2, -CR3, -NR2, =NR, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is H, a halogen, or C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 The substituent may be independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH. In certain embodiments, the substituent is -C 1~4 The heteroalkylene, heteroalkenylene, and heteroalkylynylene each independently contain one or more heteroatoms, and each heteroatom may independently be selected from N, O, and S.

[0259] In a particular embodiment, D PEG is a combined, or substituted or unsubstituted C 1~3 Alkylene, or substituted or unsubstituted C 1~3The heteroalkylene may be a substituted alkylene or substituted heteroalkylene containing one or more types of substituents, the substituents being =O, and the heteroalkylene containing one or more heteroatoms, each of which may be independently selected from N, O, and S.

[0260] In the structure of the PEG substructure, R PEG is a PEG capping group. In this case, the PEG capping group may be absent or may be -CH3, C2 alkyl, C3 alkyl, -NH2, -CH2NH2, -SC(=O)CH3, -SC(=O)CH2CH3, -CH2SC(=O)CH3, -CH2SC(=O)CH2CH3, -OH, -CH2OH, -SH, -CH2SH, -OCH3, -CH2OCH3, -CH2OCH2CH3, -C(=O)CH3, -C(=O) CH2CH3, -CH2C(=O)CH3, -CH2C(=O)CH2CH3, -NHC(=O)CH3, -NHC(=O)CH2CH3, -CH2NHC(=O)CH3, -CH2CH2NHC(=O)CH3, -CH2CH2NHC(=O)CH2CH3, -CH2NHC(=O)CH2CH3, -CH2CH2COOH, glucose, or -O-glucose. In certain embodiments, the PEG capping group may be absent or may be -CH3, -OCH3, -CH2OCH3, -C(=O)CH3, -CH2C(=O)CH3, -NHC(=O)CH3, -CH2NHC(=O)CH3, or -CH2CH2COOH. In some embodiments, the total atomic mass of the atoms belonging to the PEG capping group may be 300 doltons or less, 200 doltons or less, 150 doltons or less, 100 doltons or less, or 50 doltons or less, but is not limited to these.

[0261] In the structure of the PEG substructure, p may be an integer from 1 to 30, preferably from 1 to 10.

[0262] In the structure of the PEG substructure, [EG] refers to an ethylene glycol unit, which is defined above in the relevant paragraph.

[0263] The structure of Formula 3 described above is an example of a case in which the Fc-binding substance or Fc-binding peptide is modified, and the modifications exemplified in the structure of Formula 3 (for example, M F1 and / or M F2 Even if ) is not expressed, it should be understood that Fc-binding substances or Fc-binding peptides may further include modifications.

[0264] In some embodiments, the Fc-binding substance may include the amino acid sequence of SEQ ID NO: 02.

[0265] L PDC-(Xaa)2-H-Xa 1 -G-Xa 2 -LV-Xa 3 -CT- D P (Sequence ID: 02), In this case, Xaa, Xa 1 Xa 2 , and Xa 3 Each of these is the same as described above.

[0266] At this time, L P (L-proline residue) and C-terminus D P (D-proline residue) may optionally form a D-proline-L-proline template.

[0267] In some embodiments, the Fc-binding material may include the amino acid sequence of SEQ ID NO: 03.

[0268] CDC-(Xaa)2-H-Xa 1 -G-Xa 2 -LV-Xa 3 -CTC (Sequence ID: 03), in this case, Xaa, Xa 1 Xa 2 , and Xa 3Each of these is the same as described above.

[0269] In this case, the N-terminal cysteine ​​and the C-terminal cysteine ​​may optionally be linked by a covalent bond.

[0270] In certain embodiments, the Fc-binding substance may include the amino acid sequence of SEQ ID NO: 04: DC-(Xaa)2-H-Xa 1 -G-Xa 2 -LV-Xa 3 -CT (Sequence ID: 04), in this case, Xaa, Xa 1 Xa 2 , and Xa 3 Each of these is the same as described above.

[0271] In this case, the cysteine ​​residue adjacent to the N-terminus (the cysteine ​​linked to D in SEQ ID NO: 04) and the cysteine ​​residue adjacent to the C-terminus (the cysteine ​​linked to T in SEQ ID NO: 04) may optionally be covalently linked (for example, by a disulfide bond).

[0272] In a particular embodiment, Xa 1 This may be a diaminopropionic acid (Dap) residue, a diaminobutyric acid (Dab) residue, an ornithine (Orn) residue, or a lysine (Lys) residue.

[0273] In a particular embodiment, the Fc-binding substance is SEQ ID NO: 05: DCAWH-Xa 1 -GELVWCT (SEQ ID NO: 05) may also contain the amino acid sequence, During the ceremony, Xa 1 teeth [ka] In the formula, m is an integer from 1 to 10, and X f m is -NH2, -SH, or -C(=O)OH. In some embodiments, m may be an integer from 1 to 4.

[0274] In some embodiments, Xa 1 This may be a diaminopropionic acid (Dap) residue, a diaminobutyric acid (Dab) residue, an ornithine (Orn) residue, a lysine (Lys) residue, a 2,7-diaminoheptanoic acid residue, a 2,8-diaminooctanoic acid residue, a 2,9-diaminononanoic acid residue, a cysteine ​​residue, or a 2-aminosuberic acid residue. In certain embodiments, Xa 1 This may be a diaminopropionic acid (Dap) residue, a diaminobutyric acid (Dab) residue, an ornithine (Orn) residue, or a lysine (Lys) residue.

[0275] In this case, the cysteine ​​residue adjacent to the N-terminus (the cysteine ​​linked to D in SEQ ID NO: 05) and the cysteine ​​residue adjacent to the C-terminus (the cysteine ​​linked to T in SEQ ID NO: 05) may optionally be covalently linked (for example, by a disulfide bond).

[0276] In a particular embodiment, the Fc-binding substance has the amino acid sequence of SEQ ID NO: 06 to SEQ ID NO: 09: DCAWH-Dap-GELVWCT(Sequence ID:06); DCAWH-Dab-GELVWCT(Sequence ID: 07); DCAWH-Orn-GELVWCT(Sequence ID:08); and DCAWH-Lys-GELVWCT (Sequence ID: 09) It may include any one of the following.

[0277] In this case, the cysteine ​​residue adjacent to the N-terminus (e.g., the cysteine ​​linked to D) and the cysteine ​​residue adjacent to the C-terminus (e.g., the cysteine ​​linked to T) may optionally be covalently linked (e.g., by a disulfide bond).

[0278] Design of Fc-binding materials As previously explained, the Fc-binding substance of this application has binding activity to the Fc region of the antibody. In this case, the Fc-binding substance and the Fc region may be arranged in a specific positional relationship through interactions between amino acid residues. Typical interactions between the Fc-binding peptide of the Fc-binding substance and the Fc region of the antibody include (1) salt bonding between histidine 433 in the Fc-binding substance and the Fc region, (2) hydrogen bonding between asparagine 434 in the Fc-binding substance and the Fc region, (3) salt bonding between glutamic acid 380 in the Fc-binding substance and the Fc region, and (4) salt bonding between the Fc-binding substance and arginine 255. Such interactions and the specific positional relationships obtained from them can be identified by already known research results. (See reference [DeLano, WL, Ultsch, MH, de, AM, Vos, N., & Wells, JABaumannii (2000). Convergent solutions to binding at a protein-protein interface. Science, 287(5456), 1279-1283.]) In the design of the Fc-binding material of this application, it is important to ensure that the Fc-binding material forms a stable positional relationship with the Fc region of the antibody. This is because the compound containing the Fc-binding unit of this application, and the labeling process for the antibody using it (i.e., the process of moving the group of interest), are designed based on the positional relationship between the Fc-binding unit and the Fc region, which has been demonstrated by research.

[0279] One example of the design principle for Fc-binding substances is the amino acid sequence of Sequence ID: 05 (DCAWHXa 1 This is described by Fc-binding peptides containing GELVWCT.

[0280] Based on research data, the positional relationship between the Fc-binding peptide having the amino acid sequence of SEQ ID NO: 05 and the Fc region was simulated and is shown in Figures 1 to 3. In this simulation, the histidine residue 5 of the Fc-binding peptide forms a salt bond with glutamic acid 380 of the Fc region, and it was confirmed that this salt bond has an important effect on the positional relationship between the Fc-binding peptide and the Fc region (see the dotted line in Figure 3). For this reason, it is desirable not to change the histidine residue and its position when designing the Fc-binding peptide. Furthermore, the glutamic acid residue 8 is an electronegative residue that forms a salt bond with arginine 255 of the electronegative Fc region, and therefore, importantly, it was confirmed to affect the positional relationship between the Fc-binding peptide and the Fc region (see the dotted line in Figure 3). Therefore, this residue is preferably an acidic amino acid that can correspond to glutamic acid and may be replaced with asparagine. If these amino acid residues are changed to other amino acid residues or replaced with other functional groups, this can affect the positional relationship between the Fc-binding peptide and the Fc region by influencing intermolecular interactions. In addition, glycine 7 in SEQ ID NO: 05 is a small-volume amino acid and is required to form the folded structure of the Fc-binding peptide. Therefore, it is desirable that glycine and its position not be changed when designing the Fc-binding peptide. Figure 4 illustrates the positional relationship between the lysine residue and the Fc-binding peptide in the Fc domain. In the positional relationship, Xa 1 The lysine molecules in the Fc region located most adjacent to it were identified as lysine 246 and lysine 248 (Figure 4).

[0281] Antibodies with affinity for Fc-binding substances As described above, Fc-binding substances have binding affinity to the Fc region of antibodies.

[0282] In this specification, the term antibody is used to encompass all antibodies or fragments thereof that have affinity for Fc-binding substances, and may be recognized as antibodies even if they lack the ability to bind to specific antigens, such as in the case of Fc fragments. Furthermore, the term antibody may be interpreted to encompass monospecific antibodies, bispecific antibodies, triplicate antibodies, monoclonal antibodies, human antibodies, humanized antibodies, recombinant antibodies, chimeric antibodies, and antibody variants, etc.

[0283] Furthermore, antibodies contain an Fc region and can therefore be called Fc proteins.

[0284] In some embodiments, the antibody may include the Fc region of IgG. In some embodiments, the Fc region of the antibody may be the Fc region of IgG.

[0285] In some embodiments, the antibody may be an IgG antibody. The IgG antibody includes human IgG antibodies, humanized IgG antibodies, and chimeric IgG antibodies.

[0286] IgG is known to be classified into IgG1, IgG2, IgG3, and IgG4.

[0287] In some embodiments, the antibody may be an IgG1 antibody. The IgG1 antibody includes human IgG1 antibody, humanized IgG1 antibody, and chimeric IgG1 antibody.

[0288] In some embodiments, the antibody may include the Fc region of IgG1. The Fc region of the antibody may be the Fc region of IgG1.

[0289] In some embodiments, the antibody may be an IgG2 antibody. The IgG2 antibody includes human IgG2 antibody, humanized IgG2 antibody, and chimeric IgG2 antibody.

[0290] In some embodiments, the antibody may include the Fc region of IgG2. The Fc region of the antibody may be the Fc region of IgG2.

[0291] In some embodiments, the antibody may be an IgG3 antibody. The IgG3 antibody includes human IgG3 antibody, humanized IgG3 antibody, and chimeric IgG3 antibody.

[0292] In some embodiments, the antibody may include the Fc region of IgG3. The Fc region of the antibody may be the Fc region of IgG3.

[0293] In some embodiments, the antibody may be an IgG4 antibody. The IgG4 antibody includes human IgG4 antibody, humanized IgG4 antibody, and chimeric IgG4 antibody.

[0294] In some embodiments, the antibody may include the Fc region of IgG4. The Fc region of the antibody may be the Fc region of IgG4.

[0295] In some embodiments, the antibody may have one amino acid sequence selected from SEQ ID NOs: 14 to 18, or an amino acid sequence having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof. In certain embodiments, the antibody may have the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence having 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof.

[0296] In some embodiments, the antibody includes an IgG Fc region (for example, the Fc region of the antibody is the Fc region of IgG), and the IgG Fc region may have any one amino acid sequence selected from SEQ ID NOs: 14 to SEQ ID NOs: 18, or an amino acid sequence having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof. In certain embodiments, the antibody includes an IgG Fc region, and the IgG Fc region may have the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence having 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof.

[0297] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequences KPKDTLM (SEQ ID NO: 10) and MHEALHNH (SEQ ID NO: 11).

[0298] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequences KPKDTLM (SEQ ID NO: 10) and MHEALHNHY (SEQ ID NO: 12).

[0299] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequence GPSVFLFPPKPKDTLM (SEQ ID NO: 13).

[0300] In some embodiments, the antibody has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID NOs: 10) and MHEALHNH (SEQ ID NOs: 11). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID NOs: 10) and MHEALHNH (SEQ ID NOs: 11).

[0301] In some embodiments, the antibody has one amino acid sequence selected from SEQ ID:14-SEQ ID:15 and SEQ ID:17-SEQ ID:18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID:10) and MHEALHNHY (SEQ ID:12). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region has one amino acid sequence selected from SEQ ID:14-SEQ ID:15 and SEQ ID:17-SEQ ID:18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID:10) and MHEALHNHY (SEQ ID:12).

[0302] In some embodiments, the antibody has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially contain GPSVFLFPPKPKDTLM (SEQ ID NO: 13). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially contain GPSVFLFPPKPKDTLM (SEQ ID NO: 13).

[0303] In some embodiments, the antibody having binding affinity to the Fc-binding peptide of the present invention may be an IgG isotype antibody. In some embodiments, the antibody having binding affinity to the Fc-binding peptide of the present invention may be an IgG1 isotype antibody, an IgG2 isotype antibody, an IgG3 isotype antibody, or an IgG4 isotype antibody. In some embodiments, the antibody having binding affinity to the Fc-binding peptide of the present invention may be an IgG1 isotype antibody, an IgG2 isotype antibody, or an IgG4 isotype antibody.

[0304] As described above, in this specification, an antibody may be an antibody having binding affinity to an Fc-binding substance. For example, even if one or more of the Fab, antigen-binding region, and light and heavy chain variable regions are modified, an antibody having binding affinity to an Fc-binding substance (e.g., an antibody containing an IgG1 Fc region) may still have binding affinity to an Fc-binding substance because it contains an Fc region to which an Fc-binding substance can bind. Furthermore, even a protein having only an Fc region to which an Fc-binding substance can bind may have binding affinity to an Fc-binding substance and may be recognized as an antibody in this application. In this application, a protein that basically contains an Fc region is called an Fc protein, and in some embodiments, for convenience, an antibody may be recognized as encompassing embodiments of an Fc protein.

[0305] Furthermore, this application provides the amino acid sequence of the Fc region of human IgG1 from 237 to 444 (SEQ ID NO: 14), and the corresponding amino acid sequences of the human IgG2 Fc region (SEQ ID NO: 15), the IgG3 Fc region (SEQ ID NO: 16), the IgG4 Fc region (SEQ ID NO: 17), and the amino acid sequence of the Fc region of trastuzumab, an antibody well known in the art (SEQ ID NO: 18).

[0306] Fc-binding substances (for example, Fc-binding substances containing any one of the amino acid sequences from SEQ ID NO: 06 to SEQ ID NO: 09) are known to interact with the amino acid sequence KPKDTLM (SEQ ID NO: 10) (the sequence of amino acid residues 246-252 based on the Fc region sequence of trastuzumab) and the amino acid sequence MHEALHNHY (SEQ ID NO: 12) (the sequence of amino acid residues 428-436 based on the Fc region sequence of trastuzumab).

[0307] Structure of the Fc bonding unit Compounds containing an Fc-bonding unit contain an Fc-bonding unit. The Fc-bonding unit of a compound originates from an Fc-bonding substance. Specifically, the Fc-bonding substance or Fc-bonding unit is Xa 1 The amino acid residue represented by (for example, Xa1 It is linked to the other part of the compound containing the Fc-binding unit (by the amine group of the amino acid residue represented by ).

[0308] The Fc-binding material from which the Fc-binding unit originates was described in detail in the previous paragraph. The structure of the Fc-binding unit will be described in detail below.

[0309] In some embodiments, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently selected from any amino acid residue, Xa 1 'teeth [ka] In the formula, m is an integer from 1 to 10, and J f is -NH-, -S-, -O-, or -C(=O)-, and *** is the Xa portion that is not an Fc bond unit in a compound containing an Fc bond unit. 1 ' represents the attachment point (or connection point), and * represents Xa 1' Xa 1' This represents the attachment point, and ** is Xa 1 Xa 1 This represents the attachment point. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues.

[0310] In the structure, the cysteine ​​residues adjacent to the N-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the N-terminus) and the cysteine ​​residues adjacent to the C-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the C-terminus) may optionally be covalently linked. For example, the cysteine ​​residues adjacent to the N-terminus and the cysteine ​​residues adjacent to the C-terminus may optionally be linked by disulfide bonds. For example, the cysteine ​​residues adjacent to the N-terminus and the cysteine ​​residues adjacent to the C-terminus may optionally be in a structure containing a carbonyl group. [ka] They may be connected by a covalent bond.

[0311] In some embodiments, each Xaa may independently be any amino acid other than cysteine.

[0312] In some embodiments, Xa 1 ' may be a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated 2,8-diaminooctanoic acid residue, a conjugated 2,9-diaminononanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. In certain embodiments, Xa 1 ' may be a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, or a conjugated lysine (Lys) residue.

[0313] In the structure of the Fc-binding unit, for convenience, Xa refers to an amino acid residue conjugated to another part of the compound containing the Fc-binding unit. 1Regarding ', the term "conjugated" may be omitted or explained. For example, a conjugated diaminopropionic acid residue may be called a diaminopropionic acid residue or diaminopropionic acid. For example, a conjugated diaminobutyric acid residue may be called a diaminobutyric acid residue or diaminobutyric acid. For example, a conjugated ornithine residue may be called an ornithine residue or ornithine. For example, a conjugated lysine residue may be called a lysine residue or lysine.

[0314] When Equation 2 is illustrated together with the structure of the Fc bond unit described above, Equation 2 becomes Equation 4: [Formula 4] [ka] It can be represented by:

[0315] In some embodiments, Xa 1 ' has the following structure: [ka] It may have, In this case, m is an integer between 1 and 4. *** is a portion of a compound containing an Fc bond unit that is not an Fc bond unit, and Xa 1 This represents the attachment point. * is Xa 1 Xa 1 This represents the attachment point of ', ** is Xa 1 Xa 1 This represents the attachment point.

[0316] As described above, the Fc-binding substance, which is the origin of the Fc-binding unit, may include modifications. For example, the Fc-binding substance may include an Fc-binding peptide, and one or more modifications may be added to the Fc-binding peptide. As described above, the modifications may be at a level that does not impair the intrinsic function of the Fc-binding peptide. The Fc-binding unit may be derived from the Fc-binding substance. For example, the Fc-binding unit may further include a PEG substructure, which may be ligated to the N-terminus and / or C-terminus of the Fc-binding unit.

[0317] Hereafter, examples will be given of the structure of Fc-binding units derived from modified or unmodified Fc-binding substances (for example, modified or unmodified Fc-binding peptides with additions to the N-terminus and / or C-terminus of the amino acid sequence).

[0318] For example, the Fc bond unit has the following structure: [ka] It may have, In this case, Xaa, Xa 1 Xa 2 , and Xa 3 Each of these is the same as described above, M F1 and M F2 Each of these is described in the paragraph describing the modifications added to the Fc-binding peptide.

[0319] The exemplified structures illustrate the structure of an Fc-binding unit derived from an Fc-binding substance including modifications or an Fc-binding peptide to which modifications have been added, and thereafter, the Fc-binding unit is defined as the modified structure exemplified (e.g., M F1 and / or M F2 It is understood that this may include further modifications, even if not represented in the structure of the Fc bond unit.

[0320] In some embodiments, the Fc bonding unit has the following structure: [ka] It may have.

[0321] In this case, Xaa, Xa 1 Xa 2 , and Xa 3 Each of these is the same as described above.

[0322] In this case, the N-terminus L P (L-proline residue) and D P (D-proline residue) may optionally form a D-proline-L-proline template.

[0323] In some embodiments, the Fc bonding unit has the following structure: [ka] It may have.

[0324] In this case, Xaa, Xa 1 Xa 2 , and Xa 3 Each of these is the same as described above.

[0325] In this case, the N-terminal cysteine ​​and the C-terminal cysteine ​​may optionally be covalently linked (for example, by a disulfide bond).

[0326] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have. In this case, Xaa, Xa 1 Xa 2 , and Xa 3 Each of these is the same as described above.

[0327] In this case, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be covalently linked (for example, by a disulfide bond).

[0328] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have. During the ceremony, Xa 1 'teeth [ka] In the formula, m is an integer from 1 to 10, and J f is -NH-, -S-, -O-, or -C(=O)-, and *** is the Xa portion that is not an Fc bond unit in a compound containing an Fc bond unit. 1 ' represents the attachment point (or connection point), and * represents Xa 1' Xa 1' This represents the attachment point, and ** is Xa 1 Xa 1 This represents the attachment point.

[0329] In this case, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be covalently linked (for example, by a disulfide bond).

[0330] In a particular embodiment, Xa 1 ' may be a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated 2,8-diaminooctanoic acid residue, a conjugated 2,9-diaminononanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue.

[0331] In a particular embodiment, Xa 1'teeth [ka] And in the formula, m may be an integer from 1 to 4.

[0332] In a particular embodiment, Xa 1 ' may be a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, or a conjugated lysine (Lys) residue.

[0333] For example, in a compound containing an Fc-bonding unit, the Fc-bonding unit (FcBU) may be described by the Fc-bonding substance from which it originates, and examples of such descriptions are, but are not limited to, the following. The Fc bond unit originates from the Fc bond material. The Fc-binding substance contains the amino acid sequence of SEQ ID NO: 01, The Fc binding unit and the parts other than the Fc binding unit are Xa of the Fc binding material. 1 by (specifically, Xa 1 They are linked or conjugated (by their side chains).

[0334] As another example, in a compound containing an Fc-binding unit, the Fc-binding unit (FcBU) is as follows: The Fc binding unit contains the amino acid sequence of SEQ ID NO: 01, and the portion other than the Fc binding unit is Xa of the amino acid sequence of SEQ ID NO: 01. 1 by (specifically, Xa 1 Linked or conjugated by side chains This can be explained as follows.

[0335] The elements of compounds containing the Fc-binding unit were described in detail in the previous paragraph. The reaction of antibodies with compounds containing the Fc-binding unit will be described in detail below.

[0336] Reaction between a compound containing an Fc binding unit and an antibody The position to which the base of the object of interest is moved. As described above, a compound containing an Fc-binding unit may be used to site-specifically transfer a substance of interest to an antibody.

[0337] For example, a compound containing an Fc-binding unit may be used to move a bioorthogonal functional group or a drug to the target region of an antibody. The region in the antibody to which the group of interest is moved (e.g., the target region) may be located in the Fc region of the antibody. That is, when a compound containing an Fc-binding unit of the present invention is used, the group of interest may be moved to the Fc region of the antibody.

[0338] In some embodiments, when a compound comprising the Fc-binding unit of the present invention is used, the group of interest may be moved to one or more selected from lysine 246 (K246) and lysine 248 (K248) in the Fc region of the antibody.

[0339] In some embodiments, when a compound comprising the Fc-binding unit of the present invention is used, the group of interest may be site-specifically moved to one or more selected from K246 and K248 in the Fc region of the antibody.

[0340] For example, the number of cases in which a group of interest is moved to the target region of an antibody by contact or reaction with a compound containing the Fc binding unit of the present application may be 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 100% of all cases (i.e., cases in which the group of interest is moved to the target region and cases in which the group of interest is moved to a region other than the target region). For example, when using 100 compounds containing the Fc binding unit (where each compound containing the Fc binding unit has one group of interest), if all 100 groups of interest are moved to the target region, the number of cases in which the group of interest is moved to the target region can be described as 100%. For example, if 100 compounds containing Fc-binding units are used, and 80 of the groups of interest are moved to the target region, while 20 of the compounds containing Fc-binding units do not react with the antibody (i.e., 20 of the groups of interest are not moved to the antibody), then it can be explained that the probability of the groups of interest being moved to the target region is 100%. For example, if 100 compounds containing Fc-binding units are used, and 80 of the groups of interest are moved to the target region, while 20 of the groups of interest are moved to the antibody, but to a location other than the antibody's target region, then it can be explained that the probability of the groups of interest being moved to the target region is 80%. In this case, for example, if the groups of interest are moved to the antibody's target region, this may be determined based on the reaction time of the antibody with the compound containing the Fc-binding unit (e.g., 3 hours). In this case, the target region may be a region consisting of 20, 10, 5, or 3 amino acid residues, including lysine residues 246 (K246) and 248 (K248) of the Fc region. For example, if the target region is a region consisting of five amino acid residues including lysine residue 246 (K246) and lysine residue 248 (K248) of the Fc region, then the target region is PK 246 PK 248It may also be D (Sequence ID: 27). For example, if the target region is a region consisting of three amino acid residues including lysine residue 246 (K246) and lysine residue 248 (K248) of the Fc region, the target region is K 246 PK 248 (Sequence number: 28) is also acceptable.

[0341] In some embodiments, among the cases in which the group of interest is moved to the target region, the cases in which the group of interest is moved to lysine residue 246 (K246) of the Fc region may be 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%, 99%, or 99.5% or more, or 100%. In some embodiments, among the cases in which the group of interest is moved to the target region, the cases in which the group of interest is moved to lysine residue 248 (K248) of the Fc region may be 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99%, 99%, or 99.5% or more, or 100%.

[0342] For example, the number of cases in which the group of interest is moved to at least one of K246 and K248 in the Fc region of the antibody by contact or reaction of an antibody with a compound containing the Fc binding unit of the present application may be 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 100% of all cases (i.e., cases encompassing both cases in which the group of interest is moved to at least one of K246 and K248 in the Fc region of the antibody, and cases in which the group of interest is moved to a position other than K246 and K248).

[0343] For example, the number of cases in which the group of interest is moved to K246 of the Fc region of the antibody by contact or reaction of an antibody with a compound containing the Fc binding unit of the present application may be 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 100% of all cases (i.e., cases encompassing both cases in which the group of interest is moved to K246 of the Fc region of the antibody and cases in which the group of interest is moved to a position other than K246).

[0344] For example, the number of cases in which the group of interest is moved to K248 of the Fc region of the antibody by contact or reaction of an antibody with a compound containing the Fc binding unit of the present application may be 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 100% of all cases (i.e., cases encompassing both cases in which the group of interest is moved to K248 of the Fc region of the antibody and cases in which the group of interest is moved to a position other than K248).

[0345] In some embodiments, when a compound containing the Fc-binding unit of the present invention is used, it is possible to move the group of interest to one or more selected from K246 and K248 in the Fc region of the antibody without moving the group of interest to any other position other than one or more selected from K246 and K248. In some embodiments, when a compound containing the Fc-binding unit of the present invention is used, the movement of the group of interest to any other position other than one or more selected from K246 and K248 can be suppressed.

[0346] Compounds containing the Fc-binding unit are designed to react with the free amino group of the lysine residue of the antibody. That is, in some embodiments, when compounds containing the Fc-binding unit of the present invention are used, the group of interest may be migrated to the lysine region of the antibody's Fc region.

[0347] Furthermore, as explained in the design of Fc-binding materials, when the antibody and the Fc-binding material interact (e.g., bind), Xa 1 The lysines in the Fc region adjacent to it were described as lysine 246 and lysine 248 (lysine numbers are assigned by the EU numbering system).

[0348] For example, the amino acid sequence of trastuzumab, specifically lysine 246 and 248, is represented as follows: GPSVFLFPPK 246 PK 248 DTLM (Sequence ID: 13).

[0349] In some literature or antibodies, the lysine residues corresponding to positions 246 and 248 may be represented by numbers other than 246 and 248. In some literature, when the represented residues are amino acid residues corresponding to lysine 246 and 248, these positions are understood to be the positions of lysine 246 and 248. For example, in some literature, the amino acid residues corresponding to K246 and K248 in denosumab are called K247 and K249, respectively. As another example, in some literature, the amino acid residues corresponding to K246 and K248 in dupilumab are called K251 and K253, respectively (see literature [EP19818561.3, published EP3811978; and EP18791007.0, published EP3617235]). As described above, lysine 246 and lysine 248 can be understood to refer to lysine 246 and lysine 248, respectively, as well as the lysine residues corresponding to lysine 246 and lysine 248.

[0350] In some embodiments, when a compound containing the Fc-binding unit of the present application is used, the group of interest may be moved to one or more selected from lysine 246 (Lys246;K246) and / or lysine 248 (Lys248;K248) in the Fc region of the antibody. In certain embodiments, when a compound containing the Fc-binding unit of the present application is used, the group of interest may be moved to lysine 246 (Lys246;K246) in the Fc region of the antibody. In certain embodiments, when a compound containing the Fc-binding unit of the present application is used, the group of interest may be moved to lysine 248 (Lys248;K248) in the Fc region of the antibody. The site to which the substance of interest is moved by the reaction of the antibody with the compound containing the Fc-binding unit may be lysine 246 (Lys246;K246) and / or lysine 248 (Lys248;K248).

[0351] The reaction of antibodies with compounds containing the Fc-binding unit of this invention will be described in detail thereafter.

[0352] Description of the reaction of antibodies with compounds containing Fc binding units. Compounds containing an Fc-binding unit are directed to the Fc region of an antibody by the Fc-binding unit. This effect of directing the Fc-binding unit to a specific region of the antibody can be called the proximity effect. When described in terms of the Fc-binding substance, the Xa of the Fc-binding substance 1 The amino acid residue is adjacent to lysine 246 or lysine 248 in the Fc region of the antibody. The reaction of the compound containing the Fc-binding unit of this application with the lysine residue of the antibody (e.g., lysine 246 or lysine 248) can be illustrated by the following reaction scheme. It should be understood that the lysine residues of the antibody involved in the reaction are shown separately for illustrative purposes. [Reaction Scheme 1] [ka] .

[0353] As illustrated in reaction scheme 1 above, the reaction of an antibody with a compound containing an Fc-binding unit (exemplified as the compound of formula 2 in the reaction scheme above) may specifically be the reaction of a primary amine group (e.g., an amino group, -NH2) of the antibody with the carbonyl group of the compound containing the Fc-binding unit. For example, the reaction of an antibody with a compound containing an Fc-binding unit may be the reaction of a primary amine group in the Fc region of the antibody with the carbonyl group of the compound containing the Fc-binding unit. For example, the reaction of an antibody with a compound containing an Fc-binding unit may be the reaction of a primary amine group at lysine residue 246 in the Fc region of the antibody with the carbonyl group of the compound containing the Fc-binding unit. For example, the reaction of an antibody with a compound containing an Fc-binding unit may be the reaction of a primary amine group at lysine residue 248 in the Fc region of the antibody with the carbonyl group of the compound containing the Fc-binding unit. As shown in reaction scheme 1, the group of interest (e.g., a bioorthogonal functional group) is transferred to the antibody by the reaction of the antibody with the compound containing the Fc-binding unit.

[0354] For example, the reaction of an antibody with a compound containing an Fc binding unit can be called a nucleophilic substitution reaction. In this case, the primary amine group of the antibody can be understood to act as a nucleophile in the nucleophilic substitution reaction. For example, the reaction of an antibody with a compound containing an Fc binding unit is S N This can be called a two-step reaction. For example, the reaction of an antibody with a compound containing an Fc-binding unit can be called an acyl transfer reaction. Therefore, the terminology used to refer to the reaction is not particularly limited, and the reaction of an antibody with an Fc-binding unit can be described using terminology that is understandable to those skilled in the art.

[0355] The carbonyl group of the compound containing the Fc-binding unit that is shown to react with the primary amine group of the antibody in reaction scheme 1 is as follows: Formula 2: [Chemical formula 2] [ka] They are marked separately.

[0356] In Formula 2, the carbonyl group marked with an asterisk (-C(=O)-) represents the reaction site with the primary amine group of the antibody. In some embodiments, the carbonyl group marked with an asterisk may be called the “antibody-reacting group,” “antibody-reacting site,” or “reactive carbonyl” of the compound containing the Fc-binding unit, but is not limited to these terms.

[0357] On the one hand, as shown in reaction scheme 1, the group containing the Fc-binding unit is removed from the product by the reaction of an antibody with a compound containing the Fc-binding unit. As described above, conjugates that use a reaction mechanism in which the Fc-binding unit is removed by reaction are called traceless crosslinks, traceless reactions, or traceless conjugates. The advantages of traceless conjugates and conjugates prepared by such traceless conjugates (e.g., antibody conjugates) have been described in detail in previous studies (see references [EP19818561.3, published EP3811978; PCT patent application PCT / KR2020 / 003282, published WO2020 / 184944; and Republic of Korea patent application 10-2020-0009162, published 10-2020-0091826]). Furthermore, in the literature whose contents are cited by reference in their entirety herein [PCT Patent Application No. PCT / KR2020 / 003282, Publication No. WO2020 / 184944], it has been confirmed that when a compound containing the Fc-binding unit disclosed in the corresponding literature is used, norbornene, one example of the group of interest, is moved to K248 in the Fc region of the antibody.

[0358] As shown in reaction scheme 1, the groups removed from the compound containing the Fc-binding unit by the reaction of the antibody with the compound containing the Fc-binding unit are as follows: [ka] This can be illustrated as follows.

[0359] In some embodiments, in the exemplified eliminate group, -N(R a1 )-O- can be called a leaving group, but is not limited to them.

[0360] As shown in reaction scheme 1, the groups transferred from the compound containing the Fc-binding unit to the antibody by the reaction of the antibody with the compound containing the Fc-binding unit are as follows: [ka] This can be illustrated as follows.

[0361] Furthermore, to aid understanding, the present invention provides a schematic diagram of the reaction of an antibody with an Fc-binding unit, using the compound of formula 2-1 as an example of a compound containing an Fc-binding unit. [Reaction Scheme 2] [ka] .

[0362] Hereafter, specific embodiments of compounds containing the Fc-binding unit of the present application are disclosed. On the other hand, the specific embodiments of compounds containing the Fc-binding unit of the present application are not limited to the formulas or structures disclosed below, and specific embodiments may be derived from or newly created based on the content of the compounds containing the Fc-binding unit described above.

[0363] Specific embodiments of compounds containing Fc binding units As described above, the compound containing the Fc bond unit of this application is given by formula 2: [Formula 2] [ka] It may have a structure.

[0364] Hereafter, specific examples of compounds containing the Fc bond unit of the present application will be described in detail.

[0365] Some embodiments of the present application provide compounds of formula 2-1.

[0366] In some embodiments, Equation 2 may be represented by the following Equation 2-1. In Equation 2, J a If is -C(=O)-, then equation 2 is expressed by the following equation 2-1.

[0367] In some embodiments, the compound comprising the Fc-bonding unit of the present application is given by the following formula 2-1: [Formula 2-1] [ka] It may have a structure, During the ceremony, FcBU is an Fc-bonded unit, GOIs are the basis of the object of interest, L a This is linker A, D a This is spacer A, X is C, O, or N (i.e., -X- is -CH2-, -O-, or -NH-), R a1 H or C 1~6 It is alkyl, R a2 H or C 1~6 It is alkyl, R a3 H or C 1~6 It is alkyl.

[0368] In Equation 2-1, FcBU is an Fc-binding unit. The Fc-binding unit (FcBU) is described in detail in the previous paragraph, as described in the previous paragraph. For example, the Fc-binding unit (FcBU) is described in the "Overview of Compounds Containing Fc-Binding Units of the Application" section and the "Fc-Binding Unit (FcBU)" subsection. In Equation 2-1, GOI is the group of interest. The group of interest (GOI) is described in detail in the previous paragraph, as described in the previous paragraph. For example, the group of interest (GOI) is described in the "Overview of Compounds Containing Fc Bonding Units of the Application" and "Group of Interest (GOI)" subsections of the "Compounds Containing Fc Bonding Units" section. In Equation 2-1, L a This is linker A. Linker A(L a ) is explained in detail in the previous paragraph, and is as explained in the previous paragraph. For example, linker (L a This is described in the "Overview of the Fc-binding unit-containing compounds of this application" section and the "Linker A(L"a)" subsection of the "Compounds containing an Fc-binding unit" section. In Equation 2-1, D a This is spacer A. Spacer A(D a ) is explained in detail in the previous paragraph, and is as described in the previous paragraph. For example, Spacer A(D a This is described in the "Overview of Compounds Containing Fc Binding Units of the Present Application" section and the "Spacer A(D"a)" subsection of the "Compounds Containing Fc Binding Units" section.

[0369] Some embodiments of the present application provide compounds of formula 2-2.

[0370] In some embodiments, formula 2 may be represented by the following formula 2-2. When the group of interest (GOI) in formula 2 is a reactive group (RG), formula 2 is represented by the following formula 2-2.

[0371] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-2: [Formula 2-2] [ka] It may have a structure, During the ceremony, FcBU is an Fc-bonded unit, RG is a reactive group, L a This is linker A, D a This is spacer A, X is C, O, or N (i.e., -X- is -CH2-, -O-, or -NH-), J a These are -C(=O)-, -S-, -NH-, or -C(=NH)-, R a1 H or C 1~6 It is alkyl, R a2 H or C 1~6 It is alkyl, R a3 H or C 1~6 It is alkyl.

[0372] In Equation 2-2, FcBU is an Fc-binding unit. The Fc-binding unit (FcBU) is described in detail in the previous paragraph, as described in the previous paragraph. For example, the Fc-binding unit (FcBU) is described in the "Overview of Compounds Containing Fc-Binding Units of the Application" section and the "Fc-Binding Unit (FcBU)" subsection. In Equation 2-2, RG is a reactive group. The reactive group (RG) is described in detail in the previous paragraph, as described in the previous paragraph. For example, the reactive group (RG) is described in the "Overview of Compounds Containing Fc Bonding Units of the Application" and "Groups of Interest (GOI)" subsections of the "Compounds Containing Fc Bonding Units" section. In Equation 2-2, L a This is linker A. Linker A(L a ) is explained in detail in the previous paragraph, and is as explained in the previous paragraph. For example, linker (L aThis is described in the "Overview of the Fc-binding unit-containing compounds of this application" section and the "Linker A(L"a)" subsection of the "Compounds containing an Fc-binding unit" section. In Equation 2-2, D a This is spacer A. Spacer A(D a ) is explained in detail in the previous paragraph, and is as described in the previous paragraph. For example, Spacer A(D a This is described in the "Overview of Compounds Containing Fc Binding Units of the Present Application" section and the "Spacer A(D"a)" subsection of the "Compounds Containing Fc Binding Units" section.

[0373] Some embodiments of the present application provide compounds of formulas 2-3.

[0374] In some embodiments, formula 2 may be represented by the following formulas 2-3. In formula 2, when the group of interest (GOI) is a reactive group (RG), the reactive group is [ka] If this is the case, then Equation 2 is expressed by Equation 2-3.

[0375] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-3: [Formula 2-3] [ka] It may have a structure, During the ceremony, FcBU is an Fc-bonded unit, H RG It is a reactive substructure, D RG This is a spacer for the reactive group (spacer RG), L a This is linker A, D a This is spacer A, X is C, O, or N (i.e., -X- is -CH2-, -O-, or -NH-), J a These are -C(=O)-, -S-, -NH-, or -C(=NH)-, R a1 H or C 1~6 It is alkyl, R a2 H or C 1~6 It is alkyl, R a3 H or C 1~6 It is alkyl.

[0376] In Equation 2-3, FcBU is an Fc-binding unit. The Fc-binding unit (FcBU) is described in detail in the previous paragraph and is as described in the previous paragraph. For example, the Fc-binding unit (FcBU) is described in the "Overview of Compounds Containing Fc-Binding Units of the Application" section and the "Fc-Binding Unit (FcBU)" subsection. In equation 2-3, H RG This is a reactive substructure. Reactive substructure (H RG The reactive substructures are described in detail in the previous paragraph and are as described in the previous paragraph. For example, the reactive substructures are described in the "Overview of Compounds Containing Fc Binding Units of the Application" and "Groups of Interest (GOI)" subsections of the "Compounds Containing Fc Binding Units" section. In equation 2-3, D RG This is a spacer for the reactive group. Spacer for the reactive group (D RG The spacers of the reactive groups are described in detail in the previous paragraph and are as described in the previous paragraph. For example, the spacers of the reactive groups are described in the "Overview of Compounds Containing Fc Bonding Units of the Application" and "Groups of Interest (GOI)" subsections of the "Compounds Containing Fc Bonding Units of the Application" section. In equation 2-3, L a This is linker A. Linker A(L a) is explained in detail in the previous paragraph, and is as explained in the previous paragraph. For example, linker (L a This is described in detail in the "Overview of the Fc-binding unit-containing compounds of this application" section and the "Linker A(L"a)" subsection of the "Compounds containing Fc-binding units" section. In equation 2-3, D a This is spacer A. Spacer A(D a ) is explained in detail in the previous paragraph, and is as described in the previous paragraph. For example, Spacer A(D a This is described in the "Overview of Compounds Containing Fc Binding Units of the Present Application" section and the "Spacer A(D"a)" subsection of the "Compounds Containing Fc Binding Units" section.

[0377] Some embodiments of the present application provide compounds of formulas 2-4.

[0378] In some embodiments, Equation 2 may be represented by the following Equations 2-4. In Equation 2, J a If is -C(=O)-, then spacer A(D a ) is not replaced C 1~10 It is alkylene, R a3 is H, and equation 2 is expressed by the following equation 2-4.

[0379] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-4: [Formula 2-4] [ka] It may have a structure, During the ceremony, aa is an integer between 1 and 10. FcBU is an Fc-bonded unit, GOIs are the basis of the object of interest, L a This is linker A, X is either C or O (i.e., -X- is either -CH2- or -O-), R a1 H or C 1~6 It is alkyl, R a2 H or C 1~6 It is alkyl.

[0380] In Equation 2-4, FcBU is an Fc-binding unit. The Fc-binding unit (FcBU) is described in detail in the previous paragraph, as described in the previous paragraph. For example, the Fc-binding unit (FcBU) is described in the "Overview of Compounds Containing Fc-Binding Units of the Application" section and the "Fc-Binding Unit (FcBU)" subsection. In Formula 2-4, GOI is the group of interest. The group of interest (GOI) is described in detail in the previous paragraph, as described in the previous paragraph. For example, the group of interest (GOI) is described in the "Overview of Compounds Containing Fc Bonding Units of the Application" and "Group of Interest (GOI)" subsections of the "Compounds Containing Fc Bonding Units" section. In equation 2-4, L a This is linker A. Linker A(L a ) is explained in detail in the previous paragraph, and is as explained in the previous paragraph. For example, linker (L a This is described in the "Overview of the Fc-binding unit-containing compounds of this application" section and the "Linker A(L"a)" subsection of the "Compounds containing an Fc-binding unit" section.

[0381] Some embodiments of the present application provide compounds of formulas 2-5.

[0382] In some embodiments, Equation 2 may be represented by the following Equations 2-5.

[0383] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-5: [Formula 2-5] [ka] It may have a structure, During the ceremony, aa is an integer between 1 and 10. FcBU is an Fc-bonded unit, RG is a reactive group, L a This is linker A, X is either C or O (i.e., -X- is either -CH2- or -O-), R a1 H or C 1~6 It is alkyl, R a2 H or C 1~6 It is alkyl.

[0384] In Equation 2-5, FcBU is an Fc-binding unit. FcBU is as described in the previous paragraph. For example, FcBU is as described in the "Overview of Compounds Containing Fc-Binding Units of the Application" and the "Fc-Binding Unit (FcBU)" subsection of the "Compounds Containing Fc-Binding Units" section.

[0385] In a particular embodiment, the FcBU has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid residue other than a cysteine ​​residue. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. In the structure, the cysteine ​​residues adjacent to the N-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the N-terminus) and the cysteine ​​residues adjacent to the C-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the C-terminus) may optionally be covalently linked.

[0386] For example, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be linked by disulfide bonds.

[0387] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid other than cysteine. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. The cysteine ​​residues adjacent to the N-terminus and C-terminus are optionally linked by covalent bonds (e.g., by disulfide bonds).

[0388] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue.

[0389] In Equation 2-5, RG is a reactive group. RG is as described in the previous paragraph. For example, RG is as described in the “Overview of Compounds Containing Fc Bonding Units of the Application” and the “Group of Interest (GOI)” subsections of the “Compounds Containing Fc Bonding Units” section.

[0390] In certain embodiments, RG may include reactive substructures.

[0391] In certain embodiments, RG may include reactive substructures, and the sum of the atomic masses of all atoms constituting RG may be 3,000 doltons or less, 2,500 doltons or less, 2,000 doltons or less, 1,500 doltons or less, 1,000 doltons or less, 900 doltons or less, 800 doltons or less, 700 doltons or less, 600 doltons or less, 500 doltons or less, 400 doltons or less, 300 doltons or less, 200 doltons or less, or 100 doltons or less.

[0392] In a particular embodiment, RG has the following structure: [ka] It may have, In the formula, D RG H is a spacer for the reactive group (spacer R), RG This is a reactive substructure.

[0393] In a particular embodiment, D RG is a combined, or substituted or unsubstituted C 1~6 Alkylene, substituted or unsubstituted C 1~6 It may also be a heteroalkylene. In this case, the substituted alkylene or substituted heteroalkylene may contain one or more types of substituents, each of which substituents is -C 1~4 Alkyl and =O may be selected independently. In this case, the heteroalkylene comprises one or more heteroatoms, each of which may be selected from O, N, and S. In certain embodiments, D RG is a combined, or substituted or unsubstituted C 1~3 Alkylene, substituted or unsubstituted C 1~3 It may also be a heteroalkylene. In this case, the substituted alkylene or substituted heteroalkylene may contain one or more types of substituents, each of which substituents is -C 1~4 Alkyl and =O may be selected independently. In this case, the heteroalkylene contains one or more heteroatoms, each of which may be independently selected from O, N, and S.

[0394] In equation 2-5, L a This is linker A. Linker A is as described in the previous paragraph. For example, L a This is described in the "Overview of Compounds Containing Fc Bonding Units of the Application" section and the "Linker A(L"a)" subsection of the "Compounds Containing Fc Bonding Units" section.

[0395] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon1~60 The heteroalkylene may be a heteroalkylene containing one or more heteroatoms, each of which may be selected from O, N, and S.

[0396] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen (O).

[0397] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 20 ethylene glycol units.

[0398] In a particular embodiment, linker A is bonded to, unsubstituted C 1~50 Alkylene or unsubstituted carbon 1~50 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 16 ethylene glycol units.

[0399] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene or unsubstituted carbon 1~30 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 10 ethylene glycol units.

[0400] In a particular embodiment, linker A is bonded to, unsubstituted C 1~25 Alkylene or unsubstituted carbon 1~25The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 8 ethylene glycol units.

[0401] In a particular embodiment, linker A is bonded to, unsubstituted C 1~15 Alkylene or unsubstituted carbon 1~15 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 5 ethylene glycol units.

[0402] In certain embodiments, linker A is linked to or not replaced by C 1~6 Alkylene is also acceptable.

[0403] In certain embodiments, linker A is linked to or not replaced by C 1~3 Alkylene is also acceptable.

[0404] Some embodiments of the present application provide compounds of formulas 2-6.

[0405] In some embodiments, Equation 2 may be represented by the following Equations 2-6.

[0406] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-6: [Formula 2-6] [ka] It may have a structure, During the ceremony, aa is an integer between 1 and 10. FcBU is an Fc-bonded unit, H RG It is a reactive substructure, L a This is linker A, X is either C or O (i.e., -X- is either -CH2- or -O-), R a1 H or C 1~6 It is alkyl, R a2 H or C 1~6 It is alkyl.

[0407] In Equation 2-6, FcBU is an Fc-binding unit. An Fc-binding unit is as described in the previous paragraph. For example, FcBU is as described in the "Overview of Compounds Containing Fc-Binding Units of the Application" and the "Fc-Binding Unit (FcBU)" subsection of the "Compounds Containing Fc-Binding Units" section.

[0408] In a particular embodiment, the FcBU has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid residue that is not a cysteine ​​residue. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. In the structure, the cysteine ​​residues adjacent to the N-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the N-terminus) and the cysteine ​​residues adjacent to the C-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the C-terminus) may optionally be covalently linked.

[0409] For example, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be linked by disulfide bonds.

[0410] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid other than cysteine. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues.

[0411] In this case, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be covalently linked (for example, by a disulfide bond).

[0412] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Xa 1' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue.

[0413] In equation 2-6, H RG is a reactive substructure. Reactive substructures are as described in the previous paragraph. For example, H RG This is described in the "Overview of Compounds Containing Fc Binding Units of the Application" and "Groups of Interest (GOI)" subsections of the "Compounds Containing Fc Binding Units" section.

[0414] In a particular embodiment, H RG These may be bioorthogonal functional groups.

[0415] In a particular embodiment, H RG The structure is as follows: [ka] [ka] [ka] and [ka] It may have any one of the following: In the formula, hn is an integer between 1 and 3. R H Each of these can be independently H, or selected from -R, =O, =S, -NO2, -CR3, -NR2, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is H, halogen, C 1~6 Alkyl, C 3~10Cycloalkyl, C 3~10 Each is independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH.

[0416] In one particular embodiment, H RG The group may be selected from an azide group, a terminal alkyne group, a terminal alkene group, a cyclic alkyne (e.g., cyclooctin) group, a tetrazine group, a norbornene group, a cycloalkene (e.g., cyclooctene) group, an oxime group, and an isocyanide group. Here, cyclooctin may be any one selected from OCT cyclooctin, BCN (bicyclononine), DBCO (dibenzocyclooctin), DIBAC (aza-dibenzocyclooctin), DIBO (dibenzocyclooctinol), DIFO (difluorinated cyclooctin), BARAC (biarylazacyclooctinone), DIMAC (dimethoxyazacyclooctin), and DIFBO (difluorobenzocyclooctin). Here, cyclooctene may be selected from, for example, a cis-cyclooctene group and a trans-cyclooctene group.

[0417] In a particular embodiment, H RG This may be an azide group or a norbornene group.

[0418] In a particular embodiment, H RG This may be a click chemical functional group.

[0419] In a particular embodiment, H RG This may be selected from Diels-Alder Diene, Diels-Alder Dienophil, IEDDA Diene, and IEDDA Dienophil.

[0420] In equation 2-6, L a This is linker A. Linker A is as described in the previous paragraph. For example, L aThis is described in the "Overview of Compounds Containing Fc Bonding Units of the Application" section and the "Linker A(L"a)" subsection of the "Compounds Containing Fc Bonding Units" section.

[0421] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from O, N, and S.

[0422] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen (O).

[0423] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 20 ethylene glycol units.

[0424] In a particular embodiment, linker A is bonded to, unsubstituted C 1~50 Alkylene or unsubstituted carbon 1~50 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 16 ethylene glycol units.

[0425] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene or unsubstituted carbon 1~30The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 10 ethylene glycol units.

[0426] In a particular embodiment, linker A is bonded to, unsubstituted C 1~25 Alkylene or unsubstituted carbon 1~25 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 8 ethylene glycol units.

[0427] In a particular embodiment, linker A is bonded to, unsubstituted C 1~15 Alkylene or unsubstituted carbon 1~15 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 5 ethylene glycol units.

[0428] In certain embodiments, linker A is linked to or not replaced by C 1~6 Alkylene is also acceptable.

[0429] In certain embodiments, linker A is linked to or not replaced by C 1~3 Alkylene is also acceptable.

[0430] In a particular embodiment, R a1 is C 1~3 It may also be alkyl. In certain embodiments, R a2 H or C 1~3 Alkyl is also acceptable.

[0431] Some embodiments of the present application provide compounds of formulas 2-7.

[0432] In some embodiments, Equation 2 may be represented by the following Equations 2-7.

[0433] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-7: [Formula 2-7] [ka] It may have a structure, During the ceremony, aa is an integer between 1 and 10. FcBU is an Fc-bonded unit, H RG It is a reactive substructure, L a This is linker A, X is either C or O.

[0434] In Equation 2-7, FcBU is an Fc-binding unit. An Fc-binding unit is as described in the previous paragraph. For example, FcBU is as described in the "Overview of Compounds Containing Fc-Binding Units of the Application" and the "Fc-Binding Unit (FcBU)" subsection of the "Compounds Containing Fc-Binding Units" section.

[0435] In a particular embodiment, the FcBU has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid residue that is not a cysteine ​​residue. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. In the structure, the cysteine ​​residues adjacent to the N-terminus (i.e., the cysteine ​​residues located 2nd to 4th from the N-terminus) and the cysteine ​​residues adjacent to the C-terminus (i.e., the cysteine ​​residues located 2nd to 4th from the C-terminus) may be optionally linked by covalent bonds.

[0436] For example, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be linked by disulfide bonds.

[0437] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid other than cysteine. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. The cysteine ​​residues adjacent to the N-terminus and C-terminus are optionally linked by covalent bonds (e.g., by disulfide bonds).

[0438] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue.

[0439] In equation 2-7, H RG is a reactive substructure. Reactive substructures are as described in the previous paragraph. For example, H RG This is described in the "Overview of Compounds Containing Fc Binding Units of the Application" and "Groups of Interest (GOI)" subsections of the "Compounds Containing Fc Binding Units" section.

[0440] In a particular embodiment, H RG These may be bioorthogonal functional groups.

[0441] In a particular embodiment, H RG The structure is as follows: [ka] [ka] [ka] and [ka] It may have any one of the following: In the formula, hn is an integer between 1 and 3. R HEach of these can be independently H, or selected from -R, =O, =S, -NO2, -CR3, -NR2, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 Each is independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH.

[0442] In a particular embodiment, H RG The group may be selected from an azide group, a terminal alkyne group, a terminal alkene group, a cyclic alkyne (e.g., cyclooctin) group, a tetrazine group, a norbornene group, a cycloalkene (e.g., cyclooctene) group, an oxime group, and an isocyanide group. Here, cyclooctin may be any one selected from OCT cyclooctin, BCN (bicyclononine), DBCO (dibenzocyclooctin), DIBAC (aza-dibenzocyclooctin), DIBO (dibenzocyclooctinol), DIFO (difluorinated cyclooctin), BARAC (biarylazacyclooctinone), DIMAC (dimethoxyazacyclooctin), and DIFBO (difluorobenzocyclooctin). Here, cyclooctene may be selected from, for example, a cis-cyclooctene group and a trans-cyclooctene group.

[0443] In a particular embodiment, H RG This may be an azide group or a norbornene group.

[0444] In a particular embodiment, H RG This may be a click chemical functional group.

[0445] In a particular embodiment, H RG This may be selected from Diels-Alder Diene, Diels-Alder Dienophil, IEDDA Diene, and IEDDA Dienophil.

[0446] In equation 2-7, L a This is linker A. Linker A is as described in the previous paragraph. For example, L a This is described in the "Overview of Compounds Containing Fc Bonding Units of the Application" section and the "Linker A(L"a)" subsection of the "Compounds Containing Fc Bonding Units" section.

[0447] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be independently selected from O, N, and S.

[0448] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen (O).

[0449] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 20 ethylene glycol units.

[0450] In a particular embodiment, linker A is bonded to, unsubstituted C 1~50 Alkylene or unsubstituted carbon 1~50 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 16 ethylene glycol units.

[0451] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene or unsubstituted carbon 1~30 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 10 ethylene glycol units.

[0452] In a particular embodiment, linker A is bonded to, unsubstituted C 1~25 Alkylene or unsubstituted carbon 1~25 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 8 ethylene glycol units.

[0453] In a particular embodiment, linker A is bonded to, unsubstituted C 1~15 Alkylene or unsubstituted carbon 1~15 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 5 ethylene glycol units.

[0454] In certain embodiments, linker A is linked to or not replaced by C 1~6 Alkylene is also acceptable.

[0455] In certain embodiments, linker A is linked to or not replaced by C 1~3 Alkylene is also acceptable.

[0456] Hereafter, specific examples of compounds containing the Fc bonding unit of this application will be provided. The descriptions of each element of the Fc bonding unit are described in detail in the previous paragraph and are as described above.

[0457] Some embodiments of the present application provide compounds of formulas 2-8.

[0458] In some embodiments, Equation 2 may be represented by the following Equations 2-8.

[0459] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-8: [Formula 2-8] [ka] It may have a structure, During the ceremony, FcBU is an Fc-bonded unit, H RG It is a reactive substructure, L a This is linker A, X is either C or O.

[0460] In a particular embodiment, the FcBU has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid residue other than a cysteine ​​residue. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. In the structure, the cysteine ​​residues adjacent to the N-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the N-terminus) and the cysteine ​​residues adjacent to the C-terminus (i.e., cysteine ​​residues located 2 to 4 amino acids from the C-terminus) may optionally be covalently linked.

[0461] For example, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus may optionally be linked by disulfide bonds.

[0462] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Each of Xaa is independently any amino acid other than cysteine. Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue. Xa 2 This is a glutamic acid residue or an asparagine residue, Xa 3 These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. In this case, the cysteine ​​residue adjacent to the N-terminus and the cysteine ​​residue adjacent to the C-terminus are optionally linked by covalent bonds (for example, by disulfide bonds).

[0463] In a particular embodiment, the Fc bonding unit has the following structure: [ka] It may have, During the ceremony, Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, a conjugated lysine (Lys) residue, a conjugated 2,7-diaminoheptanoic acid residue, a conjugated cysteine ​​residue, or a conjugated 2-aminosuberic acid residue.

[0464] In a particular embodiment, H RG These may be bioorthogonal functional groups.

[0465] In a particular embodiment, H RG The structure is as follows: [ka] [ka] [ka] and [ka] It may have any one of the following structures: In the formula, hn is an integer between 1 and 3. R H Each of these can be independently H, or selected from -R, =O, =S, -NO2, -CR3, -NR2, -OR, -SR, -C(=O)R, -C(=O)CR3, -C(=O)OR, and -C(=O)NR2, where R is H, halogen, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 3~10 Each is independently selected from heterocycloalkyl, aryl, heteroaryl, -OH, -NH2, =O, =S, and -SH.

[0466] In a particular embodiment, H RGThe group may be selected from azide groups, terminal alkyne groups, terminal alkene groups, cyclic alkyne (e.g., cyclooctin) groups, tetrazine groups, norbornene groups, cycloalkene (e.g., cyclooctene) groups, oxime groups, and isocyanide groups. Here, cyclooctin may be any one selected from OCT cyclooctin, bicyclononine (BCN), dibenzocyclooctin (DBCO), aza-dibenzocyclooctin (DIBAC), dibenzocyclooctinol (DIBO), difluorinated cyclooctin (DIFO), biarylazacyclooctinone (BARAC), dimethoxyazacyclooctin (DIMAC), and difluorobenzocyclooctin (DIFBO). Here, cyclooctene may be selected from, for example, cis-cyclooctene groups and trans-cyclooctene groups.

[0467] In a particular embodiment, H RG This may be an azide group or a norbornene group.

[0468] In a particular embodiment, H RG This may be a click chemical functional group.

[0469] In a particular embodiment, H RG This may be selected from Diels-Alder Diene, Diels-Alder Dienophil, IEDDA Diene, and IEDDA Dienophil.

[0470] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may be a heteroalkylene containing one or more heteroatoms, each of which may be selected from O, N, and S.

[0471] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen (O).

[0472] In a particular embodiment, linker A is bonded to, unsubstituted C 1~60 Alkylene or unsubstituted carbon 1~60 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 20 ethylene glycol units.

[0473] In a particular embodiment, linker A is bonded to, unsubstituted C 1~50 Alkylene or unsubstituted carbon 1~50 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 16 ethylene glycol units.

[0474] In a particular embodiment, linker A is bonded to, unsubstituted C 1~30 Alkylene or unsubstituted carbon 1~30 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 10 ethylene glycol units.

[0475] In a particular embodiment, linker A is bonded to, unsubstituted C 1~25 Alkylene or unsubstituted carbon 1~25 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 8 ethylene glycol units.

[0476] In a particular embodiment, linker A is bonded to, unsubstituted C 1~15 Alkylene or unsubstituted carbon1~15 The heteroalkylene may contain one or more heteroatoms, each of which may be oxygen, and the heteroalkylene may contain 0 to 5 ethylene glycol units.

[0477] In certain embodiments, linker A is linked to or not replaced by C 1~6 Alkylene is also acceptable.

[0478] In certain embodiments, linker A is linked to or not replaced by C 1~3 Alkylene is also acceptable.

[0479] Hereafter, specific examples of compounds containing the Fc-bonding unit of the present application will be provided, and the specific examples of compounds containing the Fc-bonding unit are not limited to the structures provided below. In the previous paragraph, the description of each element of the Fc-bonding unit was described in detail, and the description of each element is as described above.

[0480] Some embodiments of the present application provide compounds of formulas 2-9.

[0481] In some embodiments, Equation 2 may be represented by the following Equations 2-9.

[0482] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-9: [Formula 2-9] [ka] It may have a structure.

[0483] Some embodiments of the present application provide compounds of formulas 2-10.

[0484] In some embodiments, Equation 2 may be represented by the following Equation 2-10.

[0485] In some embodiments, the compound comprising the Fc-bonding unit of the present application is given by the following formula 2-10: [Formula 2-10] [ka] It may have a structure.

[0486] Some embodiments of the present application provide compounds of formula 2-11.

[0487] In some embodiments, Equation 2 may be represented by the following Equation 2-11.

[0488] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-11: [Formula 2-11] [ka] It may have a structure.

[0489] Some embodiments of the present application provide compounds of formulas 2-12.

[0490] In some embodiments, Equation 2 may be represented by the following Equation 2-12.

[0491] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-12: [Formula 2-12] [ka] It may have a structure.

[0492] Some embodiments of the present application provide compounds of formula 2-13.

[0493] In some embodiments, Equation 2 may be represented by the following Equation 2-13.

[0494] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-13: [Formula 2-13] [ka] It may have a structure.

[0495] Some embodiments of the present application provide compounds of formulas 2-14.

[0496] In some embodiments, Equation 2 may be represented by the following Equation 2-14.

[0497] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-14: [Formula 2-14] [ka] It may have a structure.

[0498] Some embodiments of the present application provide compounds of formulas 2-15.

[0499] In some embodiments, Equation 2 may be represented by the following Equation 2-15.

[0500] In some embodiments, compounds containing the Fc-bonding unit of the present application are given by the following formula 2-15: [Formula 2-15] [ka] It may have a structure.

[0501] Some embodiments of the present application provide compounds of formulas 2-16.

[0502] In some embodiments, Equation 2 may be represented by the following Equation 2-16.

[0503] In some embodiments, the compound comprising the Fc-bonding unit of the present application is given by the following formula 2-16: [Formula 2-16] [ka] It may have a structure, During the ceremony, sf is an integer between 0 and 8. sg is an integer between 0 and 15. sh is an integer between 0 and 8.

[0504] Some embodiments of the present application provide compounds of formula 2-17.

[0505] In some embodiments, Equation 2 may be represented by the following Equation 2-17.

[0506] In some embodiments, the compound comprising the Fc-bonding unit of the present application is given by the following formula 2-17: [Formula 2-17] [ka] It may have a structure, During the ceremony, sf is an integer between 0 and 8. sg is an integer between 0 and 15. sh is an integer between 0 and 8.

[0507] Some embodiments of the present application provide compounds of formula 2-18.

[0508] In some embodiments, Equation 2 may be represented by the following Equation 2-18.

[0509] In some embodiments, the compound comprising the Fc-bonding unit of the present application is given by the following formula 2-18: [Formula 2-18] [ka] It may have a structure, During the ceremony, sa is an integer between 1 and 6. se is an integer between 0 and 15.

[0510] Some embodiments of the present application provide compounds of formula 2-19.

[0511] In some embodiments, Equation 2 may be represented by the following Equation 2-19.

[0512] In some embodiments, the compound comprising the Fc-bonding unit of the present application is given by the following formula 2-19: [Formula 2-19] [ka] It may have a structure, During the ceremony, sa is an integer between 1 and 6. sb is an integer between 0 and 3. sc is an integer between 1 and 15. sd is an integer between 0 and 3.

[0513] Hereafter, specific structures that compounds containing an Fc-bonding unit may have are shown. The following formulas should be understood as specific examples that compounds containing an Fc-bonding unit of the present application may take, and the scope of compounds containing an Fc-bonding unit provided by the present application should not be construed as being limited to the following examples.

[0514] In some embodiments, the compound containing the Fc binding unit is given by the following formula: [Formula 2-20] [ka] ; [Formula 2-21] [ka] ; [Formula 2-22] [ka] ; [Formula 2-23] [ka] ; [Formula 2-24] [ka] ; [Formula 2-25] [ka] ; [Formula 2-26] [ka] , and [Formula 2-27] [ka] It may have any one of the following structures. During the ceremony, sa is an integer between 1 and 6. sb is an integer between 0 and 3. sc is an integer between 1 and 15. sd is an integer between 0 and 3. se is an integer between 0 and 15. FcBU is structure [ka] It has, In the formula, Xa 1 ' is a conjugated diaminopropionic acid (Dap) residue, a conjugated diaminobutyric acid (Dab) residue, a conjugated ornithine (Orn) residue, or a conjugated lysine (Lys) residue.

[0515] Preparation of compounds containing Fc binding units The compounds containing the Fc-binding units described above may be prepared by the reaction of an Fc-binding substance with a compound for preparing compounds containing Fc-binding units (which may be called a precursor compound for compounds containing Fc-binding units).

[0516] Fc-binding substances are described in detail in the previous paragraph.

[0517] The compounds used to prepare compounds containing Fc-binding units will be described in detail below.

[0518] Compounds used to prepare compounds containing Fc-binding units may be called precursor compounds for compounds containing Fc-binding units.

[0519] Hereafter, as an example, precursor compounds for compounds containing an Fc-binding unit will be described using compounds that can be used to prepare the compound of formula 2-1.

[0520] For example, a precursor compound for a compound containing an Fc-binding unit is given by formula 5: [Formula 5] [ka] It may have a structure, In the formula, R pre This group is either an -OH group, an N-hydroxysuccinimide (NHS) group, or a pentafluorophenol group.

[0521] For example, R pre The structure is as follows: [ka] It may have any one of the following:

[0522] For example, R of the compound in formula 5 pre The Xa amino acid sequence contained in the Fc-binding substance with the adjacent carbonyl group 1 Compounds containing an Fc-binding unit (e.g., the compound of formula 2-1) may be prepared by the reaction of amino acid residues, but are not limited thereto.

[0523] Furthermore, some embodiments of the present application provide methods for preparing compounds containing Fc-bonding units.

[0524] In some embodiments, a method for preparing a compound containing an Fc-binding unit is as follows: The process may include steps of contacting or reacting an Fc-binding substance with a precursor compound for a compound containing an Fc-binding unit (for example, a compound of formula 5).

[0525] In this process, the step of contacting a precursor for a compound containing an Fc-binding unit with an Fc-binding substance may be carried out by various methods. For example, the contact step may be achieved by mixing a composition having a precursor for a compound containing an Fc-binding unit with a composition having an Fc-binding substance. Alternatively, the contact step may be achieved by adding the precursor for a compound containing an Fc-binding unit and the Fc-binding substance to a pre-prepared solution, and is not particularly limited.

[0526] Furthermore, a method for preparing a compound containing an Fc-binding unit may further include a process for obtaining a compound containing an Fc-binding unit. Furthermore, a method for preparing a compound containing an Fc-binding unit may further include a process for incubating a composition or solution containing a precursor and an Fc-binding substance for a compound containing an Fc-binding unit.

[0527] In some embodiments, the step of contacting or reacting a precursor for a compound containing an Fc-binding unit with an Fc-binding substance may be carried out under appropriate conditions. For example, the contact or reaction step may be carried out at a pH of 4 to 12. For example, the contact or reaction step may be carried out at a temperature of 10°C to 50°C. For example, the contact or reaction step may be carried out for 10 minutes to 3 days.

[0528] In addition to the precursor compounds of formula 5 described above, various compounds may be used to prepare compounds containing Fc-binding units, and the embodiments of the precursor compounds for compounds containing Fc-binding units and the embodiments of the methods for preparing compounds containing Fc-binding units are not limited to the examples described above.

[0529] Composition or kit having a compound containing an Fc binding unit Some embodiments of the present application provide compositions having compounds containing Fc-bonding units.

[0530] In some embodiments, an antibody conjugate containing a group of interest, as described below, may be prepared using a composition having a compound containing an Fc-binding unit.

[0531] In some embodiments, compositions having a compound containing an Fc-binding unit may be used for transferring a group of interest to an antibody.

[0532] Compounds containing the Fc-binding unit are as described above. In some embodiments, the compound containing the Fc-binding unit may have any one of the structures of Formula 2 and Formulas 2-1 to 2-27.

[0533] In some embodiments, a composition having a compound containing an Fc-binding unit may further contain additional elements in addition to the compound containing the Fc-binding unit. For example, the additional elements included in the composition may be, but are not limited to, pharmaceutically acceptable salts, excipients, diluents, stabilizers, and pH adjusters.

[0534] Some embodiments of the present application provide kits having compounds containing Fc-binding units.

[0535] In some embodiments, antibodies containing the group of interest described below may be prepared using a kit having a compound containing an Fc-binding unit.

[0536] In some embodiments, a kit having a compound containing an Fc-binding unit may be used for transferring a group of interest to an antibody.

[0537] Compounds containing the Fc-binding unit are as described above. In some embodiments, the compound containing the Fc-binding unit may have any one of the structures of Formula 2 and Formulas 2-1 to 2-27.

[0538] In some embodiments, a kit having a compound containing an Fc-binding unit may further include additional elements in addition to the compound containing the Fc-binding unit. For example, the additional elements included in the kit may be, but are not limited to, pharmaceutically acceptable salts, excipients, diluents, stabilizers, and pH adjusters.

[0539] The compounds containing the Fc-binding unit described above may exhibit high reaction efficiency in reactions with antibodies. For example, compounds containing the Fc-binding unit may show enhanced efficiency in the transfer of the group of interest in reactions with antibodies.

[0540] Hereafter, a method for preparing antibody conjugates using compounds containing Fc-binding units will be described in detail. The products produced by the reaction of an antibody with a compound containing an Fc-binding unit may be called, but are not limited to, an antibody containing the group of interest, a conjugate containing the group of interest (e.g., an antibody conjugate), or a modified antibody.

[0541] Length design of partial structures of compounds containing Fc binding units Compounds containing the Fc-binding unit of the present invention may be used to site-specifically transfer a group of interest to an antibody. For example, the Fc-binding unit of the present invention can be used to transfer a group of interest to K246 and / or K248 of an antibody.

[0542] The following information is provided solely for the purpose of illustrating the length design of partial structures of compounds containing the Fc bond unit of this application, and the scope of this application should not be limited by the following information.

[0543] As described above, the reaction of an antibody with a compound containing an Fc-binding unit is induced by the proximity effect of the Fc-binding unit derived from the Fc-binding substance, and the interaction between the Fc-binding substance and the antibody may be partially identified by simulation. For example, the Fc regions of the Fc-binding substance and the antibody may be arranged in a specific positional relationship, and such a positional relationship may be confirmed by simulation.

[0544] On the other hand, those skilled in the art will understand that if the reaction site of the Fc-binding unit-containing compound with the antibody (the reactive carbonyl marked with *) is adjacent to the primary amine group of the antibody's target lysine (K246 and / or K248), the reaction of the primary amine group with the reactive carbonyl marked with * of the Fc-binding unit-containing compound may proceed more successfully.

[0545] From this point onward, the positional relationship with the antibody is the amino acid sequence of sequence number 05 (DCAWHXa 1 This will be explained using an example of an Fc-binding material having GELVWCT.

[0546] Figures 5 and 6 illustrate the positional relationship between the primary amine groups lysine 246 and lysine 248 in the Fc region of the antibody and the Fc-binding substance when the antibody and the Fc-binding substance interact with each other. Specifically, in Figures 5 and 6, the Xa of the Fc-binding substance 1 The minimum and maximum distances from the beta carbon to K246 and K248 are illustrated by Figures 5 and 6. (1) Xa of the Fc bond unit of a compound containing an Fc bond unit. 1' If the distance between the beta carbon and the reactive carbonyl carbon marked with an asterisk (hereinafter generally referred to as distance A) falls within the range of the distances illustrated in Figures 5 and 6, or is similar to the illustrated distances, then the substance of interest can be expected to move more successfully to K246 and / or K248.

[0547] For illustrative purposes, Xa 1' The structure from the beta carbon to the carbon of the reactive carbonyl is the structure of Equation 2: [ka] The following examples are given: In the formula, ** represents Xa 1' The beta carbon is represented, * represents the carbon of the reactive carbonyl group, and m1 is an integer from 0 to 9.

[0548] In the above structure, if the total number of atoms located in the main chain in relation to distance A (hereinafter referred to as the main chain length) is between 8 and 20, the length formed by the structure falls within or is similar to the distances illustrated in Figures 5 and 6, and therefore it is expected that the group of interest can be more successfully moved to K246 and / or K248.

[0549] For example, if m1 is 0, D a If it is a C1 alkylene, the number of atoms located in the main chain in the above structure is 8. That is, in this case the length of the main chain is 8. Based on the above, J f and J a If each individual atom is located in the main chain, and the length of the main chain is counted accordingly, then J f It is counted as 1, J a It is counted as 1. For example, if m1 is 2, D a If it is a C3 alkylene, the length of the main chain of the structure is 12. For example, if m1 is 2 and D a If it is a C3 heteroalkenylene, the length of the main chain in the above structure is 12.

[0550] For convenience, D aThe number of atoms located in the main chain is called k. In some embodiments, the sum of m1 and k may be between 1 and 13. For example, m1 may be 0 and k may be an integer between 1 and 13. Exemplarily, m1 may be 2 and k may be an integer between 1 and 11. Exemplarily, m1 may be 3 and k may be an integer between 1 and 10. Exemplarily, m1 may be 4 and k may be an integer between 1 and 9. Exemplarily, m1 may be 4 and k may be an integer between 1 and 8. In a particular embodiment, the sum of m1 and k may be between 1 and 12. In a particular embodiment, the sum of m1 and k may be between 1 and 11. In a particular embodiment, the sum of m1 and k may be between 1 and 10.

[0551] Preparation of antibody conjugates using compounds containing Fc binding units Reactions between compounds containing Fc binding units and antibodies, and antibody conjugates prepared thereby. Compounds containing an Fc-binding unit can transfer a group of interest to an antibody through a step of contact with or reaction with the antibody. Specifically, compounds containing an Fc-binding unit can site-specifically transfer a group of interest to an antibody through a step of contact with or reaction with the antibody. In this case, the site to which the group of interest is transferred (e.g., the target site or labeling site) may be K246 and / or K248 of the antibody's Fc region. That is, an antibody conjugate containing the group of interest (e.g., site-specifically) may be prepared by a step of contacting, mixing, or reacting a compound containing an Fc-binding unit with an antibody. In this case, the group of interest in the prepared antibody conjugate may be linked to one or more of K246 and K248. Specifically, since an antibody has two heavy chains, each of which may contain lysine 246 and lysine 248 (for example, trastuzumab has a total of four labeling sites), an antibody conjugate containing one to four groups of interest can be prepared by reacting, contacting, or mixing an antibody with a compound containing an Fc-binding unit.

[0552] For example, an antibody conjugate containing one group of interest may be prepared, in which case the antibody conjugate containing one group of interest may be called a group-to-antibody ratio (GAR)1 antibody conjugate.

[0553] For example, an antibody conjugate containing two groups of interest may be prepared, in which case the antibody conjugate containing two groups of interest may be called a GAR2 antibody conjugate.

[0554] For example, an antibody conjugate containing three groups of interest may be prepared, in which case the antibody conjugate containing the three groups of interest may be called a GAR3 antibody conjugate.

[0555] For example, an antibody conjugate containing four groups of interest may be prepared, in which case the antibody conjugate containing four groups of interest may be called a GAR4 antibody conjugate.

[0556] The term "antibody conjugate containing groups of interest" is used to encompass all embodiments of antibody conjugates containing 1 to 4 groups of interest as described above. Preferably, the antibody conjugate containing groups of interest may be an antibody conjugate containing 2 groups of interest.

[0557] Figure 7 illustrates the reaction of an antibody with a compound containing the Fc-binding unit of the present invention, and the antibody conjugate containing the group of interest prepared by the reaction. As illustrated in Figure 7, the reaction of an antibody with a compound containing the Fc-binding unit may cause the group of interest to be moved to a target site in the antibody (for example, either K246 or K248 in the Fc region of the antibody).

[0558] The antibody conjugates containing 1 to 4 groups of interest will be described in more detail below.

[0559] Before describing antibody conjugates containing 1 to 4 groups of interest, the target sites that may be present in an antibody are named. Antibodies are generally known to have two heavy chains and two light chains. One of the two heavy chains may be called the first heavy chain, and the other may be called the second heavy chain. K246 and K248 present in one of the two heavy chains (the first heavy chain) may be called the first K246 and the first K248, respectively. K246 and K248 present in the other of the two heavy chains (the second heavy chain) may be called the second K246 and the second K248, respectively.

[0560] In some embodiments, the antibody conjugate containing the group of interest may contain one group of interest. In some embodiments, the one group of interest may be linked to one of the first K246, the first K248, the second K246, and the second K248. In certain embodiments, the one group of interest may be linked to one of the first K246 and the second K246. In certain embodiments, the one group of interest may be linked to one of the first K248 and the second K248.

[0561] In some embodiments, the antibody conjugate containing the group of interest may contain two groups of interest (e.g., a first group of interest and a second group of interest). In this case, the two groups of interest may be linked by two lysines selected from K246 (first K246), K248 (first K248), K246 (second K246), and K248 (second K248) of the first heavy chain. In some embodiments, of the two groups of interest, the first group of interest may be linked to one heavy chain of the antibody (first heavy chain), and the second group of interest may be linked to the other heavy chain of the antibody (second heavy chain). In some embodiments, the first group of interest may be linked to either K246 or K248 of the first heavy chain, and the second group of interest may be linked to either K246 or K248 of the second heavy chain. In certain embodiments, both groups of interest may be linked to K246. In this case, one of the two groups of interest may be linked to K246 of the first heavy chain, and the other may be linked to K246 of the second heavy chain. In certain embodiments, both groups of interest may be linked to K248. In this case, one of the two groups of interest may be linked to K248 of the first heavy chain, and the other may be linked to K248 of the second heavy chain. In certain embodiments, the two groups of interest may each be linked to K246 and K248. In this case, one of the two groups of interest (e.g., the first group of interest) may be linked to K246 of the first heavy chain, and the other (e.g., the second group of interest) may be linked to K248 of the second heavy chain. Illustratively, Figures 8 to 10 show an antibody containing a group of interest in which both groups of interest are linked to K246 (Figure 8); an antibody conjugate containing a group of interest in which both groups of interest are linked to K248 (Figure 9); and an antibody conjugate containing two groups of interest in which one of the two groups of interest (the first group of interest) is linked to K246 and the other group of interest (the second group of interest) is linked to K248 (Figure 10).

[0562] In some embodiments, the antibody conjugate containing the group of interest may contain three groups of interest. In this case, each of the three groups of interest may be linked by three lysines selected from a first K246, a first K248, a second K246, and a second K248.

[0563] In some embodiments, the antibody conjugate containing the group of interest may contain four groups of interest. In this case, the four groups of interest may be linked to a first K246, a first K248, a second K246, and a second K248, respectively.

[0564] As mentioned above, the following two elements: (1) Compounds containing an Fc binding unit; and (2) The antibody is a conjugate that uses a compound containing an Fc binding unit (e.g., an antibody conjugate containing the group of interest). It is primarily used for the preparation of [the product / service].

[0565] The elements used for preparing conjugates containing Fc-bonding units will be described in detail below.

[0566] Compounds containing element 1-Fc bond units used for the preparation of conjugates As described above, compounds containing the Fc-binding unit of this application are used for the preparation of conjugates (for example, antibody conjugates containing a group of interest). Compounds containing the Fc-binding unit of this application are described in detail in the “Compounds Containing the Fc-Binding Unit” section of this application, and the compounds containing the Fc-binding unit used for the preparation of conjugates are as described in that section.

[0567] Element 2 antibody used for conjugate preparation As described above, antibodies are used to prepare conjugates (for example, antibody conjugates containing the group of interest). The Fc-binding substance or Fc-binding unit has a binding affinity to the Fc region of the antibody.

[0568] In some embodiments, the antibody may include the Fc region of IgG. In some embodiments, the Fc region of the antibody may be the Fc region of IgG.

[0569] In some embodiments, the antibody may be an IgG antibody. The IgG antibody includes human IgG antibodies, humanized IgG antibodies, and chimeric IgG antibodies.

[0570] IgG is known to be classified into IgG1, IgG2, IgG3, and IgG4.

[0571] In some embodiments, the antibody may be an IgG1 antibody. The IgG1 antibody includes human IgG1 antibody, humanized IgG1 antibody, and chimeric IgG1 antibody.

[0572] In some embodiments, the antibody may include the Fc region of IgG1. The Fc region of the antibody may be the Fc region of IgG1.

[0573] In some embodiments, the antibody may be an IgG2 antibody. The IgG2 antibody includes human IgG2 antibody, humanized IgG2 antibody, and chimeric IgG2 antibody.

[0574] In some embodiments, the antibody may include the Fc region of IgG2. The Fc region of the antibody may be the Fc region of IgG2.

[0575] In some embodiments, the antibody may be an IgG3 antibody. The IgG3 antibody includes human IgG3 antibody, humanized IgG3 antibody, and chimeric IgG3 antibody.

[0576] In some embodiments, the antibody may include the Fc region of IgG3. The Fc region of the antibody may be the Fc region of IgG3.

[0577] In some embodiments, the antibody may be an IgG4 antibody. The IgG4 antibody includes human IgG4 antibody, humanized IgG4 antibody, and chimeric IgG4 antibody.

[0578] In some embodiments, the antibody may include the Fc region of IgG4. The Fc region of the antibody may be the Fc region of IgG4.

[0579] In some embodiments, the antibody may have one amino acid sequence selected from SEQ ID NOs: 14 to 18, or an amino acid sequence having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof. In certain embodiments, the antibody may have the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence having 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof.

[0580] In some embodiments, the antibody includes an IgG Fc region (for example, the Fc region of the antibody is the Fc region of IgG), and the IgG Fc region may have any one amino acid sequence selected from SEQ ID NOs: 14 to SEQ ID NOs: 18, or an amino acid sequence having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof. In certain embodiments, the antibody includes an IgG Fc region, and the IgG Fc region may have the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence having 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof.

[0581] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequences KPKDTLM (SEQ ID NO: 10) and MHEALHNH (SEQ ID NO: 11).

[0582] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequences KPKDTLM (SEQ ID NO: 10) and MHEALHNHY (SEQ ID NO: 12).

[0583] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequence GPSVFLFPPKPKDTLM (SEQ ID NO: 13).

[0584] In some embodiments, the antibody has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID NOs: 10) and MHEALHNH (SEQ ID NOs: 11). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID NOs: 10) and MHEALHNH (SEQ ID NOs: 11).

[0585] In some embodiments, the antibody has one amino acid sequence selected from SEQ ID:14-SEQ ID:15 and SEQ ID:17-SEQ ID:18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID:10) and MHEALHNHY (SEQ ID:12). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region has one amino acid sequence selected from SEQ ID:14-SEQ ID:15 and SEQ ID:17-SEQ ID:18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially include the amino acid sequences of KPKDTLM (SEQ ID:10) and MHEALHNHY (SEQ ID:12).

[0586] In some embodiments, the antibody has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially contain GPSVFLFPPKPKDTLM (SEQ ID NO: 13). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region has one amino acid sequence selected from SEQ ID NOs: 14 to 18, or from those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially contain GPSVFLFPPKPKDTLM (SEQ ID NO: 13).

[0587] In some embodiments, the antibody having binding affinity to the Fc-binding substance or peptide of the present invention may be an IgG isotype antibody. In some embodiments, the antibody having binding affinity to the Fc-binding substance or peptide of the present invention may be an IgG1 isotype antibody, an IgG2 isotype antibody, an IgG3 isotype antibody, or an IgG4 isotype antibody. In some embodiments, the antibody having binding affinity to the Fc-binding substance or peptide of the present invention may be an IgG1 isotype antibody, an IgG2 isotype antibody, or an IgG4 isotype antibody.

[0588] The inventors of the present application have confirmed that, with respect to various types of antibodies, the group of interest (e.g., bioorthogonal functional groups) is transferred to the antibody by reaction with a compound containing the Fc-binding unit of the present application. More specifically, the inventors of the present application have confirmed that, when a compound containing the Fc-binding unit of the present application (compound 9 of the examples) is used, the group of interest (e.g., azide group) is transferred to trastuzumab (IgG1 type antibody), IgG1 type anti-CLDN18.2 antibody, IgG1 type anti-CD154 antibody, denosumab (IgG2 type antibody), and dupilumab, respectively.

[0589] In some embodiments, the antibody is adalimumab (Humira), rituximab (Rituxan), trastuzumab (Herceptin), bevacizumab (Avastin), infliximab (Remicade), pembrolizumab (Keytruda), nivolumab (Opdivo), eculizumab (Soliris), alemtuzumab (Remtrada, Campus), daratumumab (Darzalex), ipilimumab (Yervoy), golimumab (Simponi), tocilizumab (Actemra), ranibizumab (Lucentis), secuk It may also be any one selected from numab (Cosentyx), ixekizumab (Taltz), dupilumab (Dupixent), denosumab, ustekinumab (Stelara), palivizumab (Synagis), durvalumab (Imfinzi), atezolizumab (Tecentriq), omalizumab (Xolair), vedolizumab (Entyvio), absiximab (Leopro), basiliximab (Symlect), alefacept (Amevib), daclizumab (Zimbrita), and elotuzumab (Empliciti).

[0590] In some embodiments, the antibody may be an antibody having binding properties to any one of the following: EpCAM, CD2, CD3, CD4, CD5, CD6, CD11, CD19, CD20, CD22, CD26, CD30, CD33, CD37, CD38, CD40, CD44, CD56, CD79, CD105, CD138, EphA receptor, EphB receptor, EGFR, EGFRvIII, HER2, HER3, mesothelin, crypto, alpha v beta 3, alpha v beta 5, nectin-4, TROP2, PD1, PD-L1, BCMA, B3H7, FOLR-a, tissue factor, claudin 1 (CLDN1), claudin 3 (CLDN3), claudin 4 (CLDN4), claudin 6 (CLDN6), claudin 18.2 (CLDN18.2), and alpha v beta 6 integrin.

[0591] In some embodiments, the antibody may be an anti-CLDN18.2 antibody (see reference [Republic of Korea Patent Application No. 10-2021-7023724]).

[0592] In some embodiments, the heavy chain of the anti-CLDN18.2 antibody may include CDRH1 having an amino acid sequence with sequence number 19 (TYGVH) or 90% or more sequence identity thereto, CDRH2 having an amino acid sequence with sequence number 20 (VIWAGGSTNYNSALMS) or 90% or more sequence identity thereto, and CDRH3 having an amino acid sequence with sequence number 21 (AAYYGNGLDY) or 90% or more sequence identity thereto. In certain embodiments, the anti-CLDN18.2 antibody may have two heavy chains, each heavy chain may include CDRH1 having the amino acid sequence of sequence number 19, CDRH2 having the amino acid sequence of sequence number 20, and CDRH3 having the amino acid sequence of sequence number 21.

[0593] In some embodiments, the light chain of the anti-CLDN18.2 antibody may include CDRL1 having an amino acid sequence with sequence number 22 (KSSQTLLNSGNQKNYLT) or 90% or more sequence identity thereto, CDRL2 having an amino acid sequence with sequence number 23 (WASTGES) or 90% or more sequence identity thereto, and CDRL3 having an amino acid sequence with sequence number 24 (QNAYFYPFT) or 90% or more sequence identity thereto. In certain embodiments, the anti-CLDN18.2 antibody may have two light chains, each light chain may include CDRL1 having the amino acid sequence of sequence number 22, CDRL2 having the amino acid sequence of sequence number 23, and CDRL3 having the amino acid sequence of sequence number 24.

[0594] In some embodiments, the heavy chain of the anti-CLDN18.2 antibody may include CDRH1 having an amino acid sequence having sequence identity with SEQ ID NO: 19 or 90% or more of it, CDRH2 having an amino acid sequence having sequence identity with SEQ ID NO: 20 or 90% or more of it, and CDRH3 having an amino acid sequence having sequence identity with SEQ ID NO: 21 or 90% or more of it. The light chain of the anti-CLDN18.2 antibody may include CDRL1 having an amino acid sequence having sequence identity with SEQ ID NO: 22 or 90% or more of it, CDRL2 having an amino acid sequence having sequence identity with SEQ ID NO: 23 or 90% or more of it, and CDRL3 having an amino acid sequence having sequence identity with SEQ ID NO: 24 or 90% or more of it. In certain embodiments, the anti-CLDN18.2 antibody may have two heavy chains comprising CDRH1 having the amino acid sequence of SEQ ID NO: 19, CDRH2 having the amino acid sequence of SEQ ID NO: 20, and CDRH3 having the amino acid sequence of SEQ ID NO: 21, and two light chains comprising CDRL1 having the amino acid sequence of SEQ ID NO: 22, CDRL2 having the amino acid sequence of SEQ ID NO: 23, and CDRL3 having the amino acid sequence of SEQ ID NO: 24.

[0595] In some embodiments, the anti-CLDN18.2 antibody may comprise a heavy chain having an amino acid sequence having 90% or greater sequence identity with SEQ ID NO: 25, and a light chain having an amino acid sequence having 90% or greater sequence identity with SEQ ID NO: 26. In certain embodiments, the anti-CLDN18.2 antibody may comprise a heavy chain having the amino acid sequence of SEQ ID NO: 25, and a light chain having the amino acid sequence of SEQ ID NO: 26. Specifically, the anti-CLDN18.2 antibody may comprise two heavy chains having the amino acid sequence of SEQ ID NO: 25, and two light chains having the amino acid sequence of SEQ ID NO: 26.

[0596] The binding affinity of an Fc-binding substance to an antibody or the Fc region of an antibody can be expressed as a dissociation constant (Kd). In some embodiments, the dissociation constant (Kd) of the Fc-binding substance to the antibody is 10 μM, 1 μM (1 × 10⁻¹⁶). -6 M), 900nM, 800nM, 700nM, 600nM, 500nM, 450nM, 400nM, 350nM, 300nM, 250nM, 200nM, 180nM, 160nM , 140nM, 120nM, 100nM, 90nM, 80nM, 70nM, 60nM, 50nM, 40nM, 30nM, 20nM, 10nM, 5nM, 2nM, 1nM (1×10 -9 The Fc-binding constant (Kd) of the Fc-binding substance to the Fc domain of the antibody may be 10 μM, 1 μM (1 × 10⁻¹⁰), 0.5 nM, 0.1 nM, 0.05 nM, or 0.01 nM or less, or may be set within the range set by any two values ​​selected from the above values. In some embodiments, the dissociation constant (Kd) of the Fc-binding substance to the Fc domain of the antibody is 10 μM, 1 μM (1 × 10⁻¹⁰). -6 M), 900nM, 800nM, 700nM, 600nM, 500nM, 450nM, 400nM, 350nM, 300nM, 250nM, 200nM, 180nM, 160nM , 140nM, 120nM, 100nM, 90nM, 80nM, 70nM, 60nM, 50nM, 40nM, 30nM, 20nM, 10nM, 5nM, 2nM, 1nM (1×10 -9 M) may be 0.5nM, 0.1nM, 0.05nM, or 0.01nM or less, or may be within the range set by any two values ​​selected from the above values, but is not limited to these.

[0597] Method for preparing antibody conjugates using compounds containing Fc binding units Some embodiments of the present application provide methods for preparing antibody conjugates containing a group of interest. These methods may be called methods for site-specific preparation of antibody conjugates containing a group of interest, methods for transferring a group of interest to an antibody, methods for site-specific transfer of a group of interest to an antibody, and methods for site-specific transfer of a reactive group (e.g., a bioorthogonal functional group) to an antibody. As described above, the methods may be freely named depending on the purpose to be achieved by the reaction of an antibody with a compound containing an Fc-binding unit.

[0598] Some embodiments of the present invention provide a method for preparing an antibody conjugate containing a group of interest, the method comprising the step of contacting an antibody with a compound containing an Fc-binding unit.

[0599] In this context, the term "contact stage" may be replaced with terms such as "reaction stage" or "mixing stage."

[0600] In this context, the compound containing the Fc-bonding unit is the compound containing the Fc-bonding unit provided by this application. For example, the compound containing the Fc-bonding unit may be the compound of formula 2. For example, the compound containing the Fc-bonding unit may be any one of the compounds of formula 2 and formulas 2-1 to 2-27 (i.e., the compound containing the Fc-bonding unit may be a compound having the structure of any one of the formulas 2 and 2-1 to 2-27). The compounds containing the Fc-bonding unit of this application and the elements contained therein are described in detail in the "Compounds Containing Fc-Bonding Units" section, and the compounds containing the Fc-bonding unit and the elements contained therein are as described in the previous paragraph.

[0601] In this process, the step of contacting the compound containing the Fc-binding unit with the antibody may be carried out by various methods. For example, the contact step may be achieved by mixing a composition having the compound containing the Fc-binding unit with a composition having the antibody. Alternatively, the contact step may be achieved by adding the compound containing the Fc-binding unit and the antibody to the preparation solution, and is not particularly limited.

[0602] In some embodiments, the antibody conjugate containing the group of interest may be prepared by contacting an antibody with a compound containing an Fc-binding unit. In some embodiments, in the antibody conjugate containing the group of interest, the group of interest may be linked to one or more selected from K246 and K248 of the Fc region of the antibody. In some embodiments, in the antibody conjugate containing the group of interest, the group of interest may be linked to K246 of the Fc region of the antibody. In some embodiments, in the antibody conjugate containing the group of interest, the group of interest may be linked to K248 of the Fc region of the antibody. In some embodiments, the antibody conjugate containing the group of interest may contain 1 to 4 groups of interest. In some embodiments, the antibody conjugate containing the group of interest may contain 1 group of interest. In certain embodiments, the antibody conjugate containing the group of interest may contain 2 groups of interest.

[0603] In some embodiments, the group of interest may be site-specifically transferred to the antibody (e.g., to the target region of the antibody) by contact of the antibody with a compound containing an Fc-binding unit. For example, the target region may consist of 1 to 20, 1 to 10, 1 to 5, or 1 to 3 consecutive amino acid residues, including K246 and K248 of the Fc region. In some embodiments, the group of interest may be transferred to one or more lysine residues selected from K246 and K248 of the Fc region of the antibody by contact of the antibody with a compound containing an Fc-binding unit. In some embodiments, the group of interest may be transferred to K246 of the Fc region of the antibody by contact of the antibody with a compound containing an Fc-binding unit. In some embodiments, the group of interest may be transferred to K248 of the Fc region of the antibody by contact of the antibody with a compound containing an Fc-binding unit.

[0604] In some embodiments, the contact or reaction of an antibody with a compound containing an Fc-binding unit may be carried out in a solution or composition.

[0605] In some embodiments, the contact or reaction of an antibody with a compound containing an Fc-binding unit may be carried out at any one pH selected from pH 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, and 12, or within a range set by two values ​​selected from the above values. In some embodiments, the contact or reaction of an antibody with a compound containing an Fc-binding unit may be carried out under pH conditions of 5-10, 6-10, 7-10, 5-9, 5-8, 6-9, 6-8, 7-9, or 7-8. In certain embodiments, the reaction of an antibody with a compound containing an Fc-binding unit may be carried out under pH conditions of 6.5-8.5 or 7-8. In certain embodiments, the reaction of an antibody with a compound containing an Fc-binding unit may be carried out at approximately pH 7.4.

[0606] In some embodiments, the contact or reaction of an antibody with a compound containing an Fc-binding unit may be carried out at 10°C to 50°C, 10°C to 45°C, 15°C to 45°C, 15°C to 40°C, 20°C to 45°C, 20°C to 40°C, 20°C to 35°C, 20°C to 30°C, 25°C to 45°C, 25°C to 40°C, 25°C to 35°C, or 20°C to 30°C. In some embodiments, the reaction of an antibody with a compound containing an Fc-binding unit may be carried out at room temperature.

[0607] In some embodiments, a method for preparing an antibody conjugate containing a group of interest may further include the step of incubating a solution (or composition) having a compound containing an Fc-binding unit and the antibody conjugate. Optionally, processes such as stirring or vortexing may be performed during incubation. Incubation may be performed for a period of time of approximately 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, 30 hours, 36 hours, 42 hours, 48 ​​hours, 60 hours, or 72 hours or longer, and the duration is not particularly limited.

[0608] In some embodiments, a method for preparing an antibody conjugate containing a group of interest may further include a step of obtaining an antibody conjugate containing the group of interest. In this step, obtaining an antibody conjugate containing the group of interest may include, but is not limited to, a step of purifying the antibody conjugate containing the group of interest.

[0609] For example, a method for preparing an antibody conjugate containing a group of interest is: (a) A step of preparing a composition having a compound containing an Fc-binding unit and an antibody by mixing the compound containing the Fc-binding unit and the antibody; (b) A step of incubating a composition having a compound containing an Fc binding unit and an antibody; and (c) Step of obtaining an antibody conjugate containing the group of interest from the incubated composition. It may include (see Figure 11).

[0610] Advantages of using compounds containing the Fc-binding unit of the present invention As described above, compounds containing the Fc-binding unit of the present invention may exhibit enhanced reaction efficiency in reactions with antibodies. For example, the reaction of an antibody with a compound containing the Fc-binding unit may have an enhanced reaction rate. Accordingly, the yield of the conjugate prepared by the reaction of an antibody with a compound containing the Fc-binding unit may be increased, or the time required to prepare the conjugate may be reduced. The advantages of using compounds containing the Fc-binding unit of the present invention, i.e., the advantages of the method for preparing antibody conjugates containing the group of interest provided by the present invention, will be described below.

[0611] As described above, when compounds containing the Fc binding unit in related technologies (compounds of formula 1-1) are used, the reaction efficiency of the compound of formula 1-1 with the antibody is not good, resulting in problems such as the antibody conjugate containing the group of interest not being prepared, or the preparation of the antibody conjugate containing the group of interest taking a long time. According to experiments conducted by the inventors of the present invention, even though the antibody was reacted with the compound of formula 1-1 for 3 hours, only a 5% antibody conjugate was obtained, and the obtained antibody conjugate was confirmed to be a GAR1 antibody conjugate (see Example 02).

[0612] In contrast, it has been confirmed that when a compound containing the Fc-binding unit of the present invention is used, the yield of antibody conjugate preparation is improved.

[0613] In some embodiments, the reaction efficiency may be calculated based on the amount of antibody conjugates containing the group of interest prepared by the reaction over a predetermined period of time. The reaction efficiency may also be calculated, for example, from the yield rate of antibody conjugates prepared by the reaction over a predetermined period of time. For example, if 60 antibody conjugates containing the group of interest are prepared from the initially added 100 antibodies by a 1-hour reaction, the yield rate of antibody conjugates containing the group of interest is 60%. For example, if 80 antibody conjugates containing the group of interest are prepared from the initially added 100 antibodies by a 3-hour reaction, the yield rate of antibody conjugates containing the group of interest is 80%. In this case, the antibody conjugates containing the group of interest may include all of the GAR1, GAR2, GAR3, and GAR4 antibody conjugates. In this case, the antibody conjugates containing the group of interest may refer to the GAR2 antibody conjugate. For example, if a 3-hour reaction prepares 60 GAR1 antibody conjugates and 20 GAR2 antibody conjugates from the initially added 100 antibodies, the yield of the GAR2 antibody conjugates is 20%. In some embodiments, the reaction efficiency may be calculated based on the amount of antibody-payload conjugates described below. In this case, the antibody-payload conjugates may include all of the following: payload-antibody ratio (PAR)1 antibody conjugates, in which one payload (i.e., one cargo substructure) is linked to an antibody unit; PAR2 antibody conjugates, in which two payloads are linked to an antibody unit; PAR3 antibody conjugates, in which three payloads are linked to an antibody unit; and PAR4 antibody conjugates, in which four payloads are linked to an antibody unit. For example, if a 3-hour reaction prepares 60 PAR2 antibody conjugates from the initially added 100 antibodies, the yield is 60%. The antibody conjugate used as the basis for the yield may be selected as appropriate. For example, the antibody conjugate used as the basis for the yield rate may be a GAR1 and GAR2 antibody conjugate.For example, the antibody conjugate used as the basis for yield rate may be PAR1 and PAR2 antibody conjugates. For example, the antibody conjugate used as the basis for yield rate may be GAR2 antibody conjugates. For example, the antibody conjugate used as the basis for yield rate may be PAR2 antibody conjugates.

[0614] In some embodiments, the yield of the antibody conjugate containing the group of interest obtained by the reaction over a predetermined period of time may be 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% or higher. Hereinafter, the predetermined period may be, for example, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2.5 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, 30 hours, 36 hours, 42 hours, 48 ​​hours, 60 hours, or 72 hours or longer.

[0615] Compositions or kits for preparing antibody conjugates containing a group of interest Some embodiments of the present application provide compositions or kits for preparing antibody conjugates containing a group of interest. The compositions or kits for preparing antibody conjugates containing a group of interest may be used to prepare antibody conjugates containing a group of interest. The compositions or kits for preparing antibody conjugates containing a group of interest comprise a compound containing an Fc-binding unit and an antibody. The compounds containing the Fc-binding unit and the antibody are as described above.

[0616] Some embodiments of the present application provide compositions for preparing antibody conjugates containing a group of interest.

[0617] In some embodiments, a composition for preparing an antibody conjugate containing a group of interest may further include additional elements in addition to a compound containing an Fc-binding unit and an antibody. For example, the additional elements included in the composition may be, but are not limited to, carriers, excipients, diluents, stabilizers, and pH adjusters.

[0618] Some embodiments of the present invention provide kits for preparing antibody conjugates containing a group of interest.

[0619] In some embodiments, a kit for preparing an antibody conjugate containing a group of interest may further include additional elements in addition to the compound containing the Fc-binding unit and the antibody. For example, the additional elements included in the kit may be, but are not limited to, carriers, excipients, diluents, stabilizers, and pH adjusters.

[0620] Hereafter, antibody conjugates containing the group of interest, prepared by the reaction or contact of an antibody with a compound containing an Fc-binding unit, will be described in detail.

[0621] Overview of antibody conjugates containing the group of interest As described above, an antibody conjugate containing the group of interest may be prepared by reacting an antibody with a compound containing an Fc-binding unit.

[0622] The compound represented by equation 6 below may be called an antibody conjugate containing the group of interest.

[0623] Some embodiments of this application are given by the following formula 6: [Formula 6] [ka] The present invention provides a compound having the structure described herein.

[0624] In Equation 6, Ab is an antibody unit.

[0625] In equation 6, L b This is linker B.

[0626] In Equation 6, the GOI is a base of interest. The base of interest is described in detail in the previous paragraph, and is as described in the previous paragraph.

[0627] In equation 6, n is an integer between 1 and 4.

[0628] In this case, in formula 6, the group of interest may be linked to one or more of the lysine residues 246 (K246) and 248 (K248) of the Fc region of the antibody unit.

[0629] From here on, each element of the compound in Equation 6 will be explained in detail.

[0630] Antibody unit An antibody unit is derived from an antibody and can be called a conjugated antibody. Furthermore, since the structure of an antibody unit is the same as that of the antibody from which the antibody unit originates, except for the conjugated portion, an antibody unit can be called an antibody, and the explanation given in the paragraph describing antibodies can be directly applied. Figure 12 compares the structures of an antibody and an antibody unit by highlighting the conjugated portion. As illustrated in Figure 12, an antibody unit derived from an antibody and an antibody from which an antibody unit originates are structurally nearly identical.

[0631] In some embodiments, the antibody (or antibody unit) may include the Fc region of IgG. In some embodiments, the Fc region of the antibody may be the Fc region of IgG.

[0632] In some embodiments, the antibody may be an IgG antibody. The IgG antibody includes human IgG antibodies, humanized IgG antibodies, and chimeric IgG antibodies.

[0633] IgG is known to be classified into IgG1, IgG2, IgG3, and IgG4.

[0634] In some embodiments, the antibody may be an IgG1 antibody. The IgG1 antibody includes human IgG1 antibody, humanized IgG1 antibody, and chimeric IgG1 antibody.

[0635] In some embodiments, the antibody may include the Fc region of IgG1. The Fc region of the antibody may be the Fc region of IgG1.

[0636] In some embodiments, the antibody may be an IgG2 antibody. The IgG2 antibody includes human IgG2 antibody, humanized IgG2 antibody, and chimeric IgG2 antibody.

[0637] In some embodiments, the antibody may include the Fc region of IgG2. The Fc region of the antibody may be the Fc region of IgG2.

[0638] In some embodiments, the antibody may be an IgG3 antibody. The IgG3 antibody includes human IgG3 antibody, humanized IgG3 antibody, and chimeric IgG3 antibody.

[0639] In some embodiments, the antibody may include the Fc region of IgG3. The Fc region of the antibody may be the Fc region of IgG3.

[0640] In some embodiments, the antibody may be an IgG4 antibody. The IgG4 antibody includes human IgG4 antibody, humanized IgG4 antibody, and chimeric IgG4 antibody.

[0641] In some embodiments, the antibody may include the Fc region of IgG4. The Fc region of the antibody may be the Fc region of IgG4.

[0642] In some embodiments, the antibody may have one amino acid sequence selected from SEQ ID NOs: 14 to 18, or an amino acid sequence having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof. In certain embodiments, the antibody may have the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence having 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof.

[0643] In some embodiments, the antibody may include an IgG Fc region (for example, the Fc region of the antibody may be the Fc region of IgG), and the IgG Fc region may have any one amino acid sequence selected from SEQ ID NOs: 14 to SEQ ID NOs: 18, or an amino acid sequence having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof. In certain embodiments, the antibody may include an IgG Fc region, and the IgG Fc region may have the amino acid sequence of SEQ ID NO: 14, or an amino acid sequence having 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof.

[0644] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequences KPKDTLM (SEQ ID NO: 10) and MHEALHNH (SEQ ID NO: 11).

[0645] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequences KPKDTLM (SEQ ID NO: 10) and MHEALHNHY (SEQ ID NO: 12).

[0646] In some embodiments, the antibody or the Fc region of the antibody may include the amino acid sequence GPSVFLFPPKPKDTLM (SEQ ID NO: 13).

[0647] In some embodiments, the antibody may have one amino acid sequence selected from SEQ ID NOs: 14 to 18, or any of those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may basically contain the amino acid sequences of KPKDTLM (SEQ ID NOs: 10) and MHEALHNH (SEQ ID NOs: 11). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region may have one amino acid sequence selected from SEQ ID NOs: 14 to 18, or any of those sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may basically contain the amino acid sequences of KPKDTLM (SEQ ID NOs: 10) and MHEALHNH (SEQ ID NOs: 11).

[0648] In some embodiments, the antibody may have any one amino acid sequence selected from SEQ ID NOs: 14-15 and SEQ ID NOs: 17-18, or any amino acid sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof, and may also include the amino acid sequences of KPKDTLM (SEQ ID NO: 10) and MHEALHNHY (SEQ ID NO: 12). In some embodiments, the antibody includes an IgG Fc region (for example, the Fc region of the antibody is the Fc region of IgG), and the IgG Fc region may have any one amino acid sequence selected from SEQ ID NOs: 14-15 and SEQ ID NOs: 17-18, or any amino acid sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity thereof, and may also include the amino acid sequences of KPKDTLM (SEQ ID NO: 10) and MHEALHNHY (SEQ ID NO: 12).

[0649] In some embodiments, the antibody may have any one amino acid sequence selected from SEQ ID NOs: 14 to 18, or any amino acid sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially contain GPSVFLFPPKPKDTLM (SEQ ID NO: 13). In some embodiments, the antibody includes an IgG Fc region, and the IgG Fc region may have any one amino acid sequence selected from SEQ ID NOs: 14 to 18, or any amino acid sequences having 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or greater sequence identity, and may essentially contain the amino acid sequence of GPSVFLFPPKPKDTLM (SEQ ID NO: 13).

[0650] In some embodiments, the antibody having binding affinity to the Fc-binding substance or peptide of the present invention may be an IgG isotype antibody. In some embodiments, the antibody having binding affinity to the Fc-binding substance or peptide of the present invention may be an IgG1 isotype antibody, an IgG2 isotype antibody, an IgG3 isotype antibody, or an IgG4 isotype antibody. In some embodiments, the antibody having binding affinity to the Fc-binding substance or peptide of the present invention may be an IgG1 isotype antibody, an IgG2 isotype antibody, or an IgG4 isotype antibody.

[0651] In some embodiments, the antibody is adalimumab (Humira), rituximab (Rituxan), trastuzumab (Herceptin), bevacizumab (Avastin), infliximab (Remicade), pembrolizumab (Keytruda), nivolumab (Opdivo), eculizumab (Soliris), alemtuzumab (Remtrada, Campus), daratumumab (Darzalex), ipilimumab (Yervoy), golimumab (Simponi), tocilizumab (Actemra), ranibizumab (Lucentis), secuk It may also be any one selected from numab (Cosentyx), ixekizumab (Taltz), dupilumab (Dupixent), denosumab, ustekinumab (Stelara), palivizumab (Synagis), durvalumab (Imfinzi), atezolizumab (Tecentriq), omalizumab (Xolair), vedolizumab (Entyvio), absiximab (Leopro), basiliximab (Symlect), alefacept (Amevib), daclizumab (Zimbrita), and elotuzumab (Empliciti).

[0652] In some embodiments, the antibody may be an antibody having binding properties to any one of the following: EpCAM, CD2, CD3, CD4, CD5, CD6, CD11, CD19, CD20, CD22, CD26, CD30, CD33, CD37, CD38, CD40, CD44, CD56, CD79, CD105, CD138, EphA receptor, EphB receptor, EGFR, EGFRvIII, HER2, HER3, mesothelin, crypto, alpha v beta 3, alpha v beta 5, nectin-4, TROP2, PD1, PD-L1, BCMA, B3H7, FOLR-a, tissue factor, claudin 1 (CLDN1), claudin 3 (CLDN3), claudin 4 (CLDN4), claudin 6 (CLDN6), claudin 18.2 (CLDN18.2), and alpha v beta 6 integrin.

[0653] In some embodiments, the antibody may be an anti-CLDN18.2 antibody (see reference [Republic of Korea Patent Application No. 10-2021-7023724]).

[0654] In some embodiments, the heavy chain of the anti-CLDN18.2 antibody may include CDRH1 having an amino acid sequence with sequence number 19 (TYGVH) or 90% or more sequence identity thereto, CDRH2 having an amino acid sequence with sequence number 20 (VIWAGGSTNYNSALMS) or 90% or more sequence identity thereto, and CDRH3 having an amino acid sequence with sequence number 21 (AAYYGNGLDY) or 90% or more sequence identity thereto. In certain embodiments, the anti-CLDN18.2 antibody may have two heavy chains, each heavy chain may include CDRH1 having the amino acid sequence of sequence number 19, CDRH2 having the amino acid sequence of sequence number 20, and CDRH3 having the amino acid sequence of sequence number 21.

[0655] In some embodiments, the light chain of the anti-CLDN18.2 antibody may include CDRL1 having an amino acid sequence with sequence number 22 (KSSQTLLNSGNQKNYLT) or 90% or more sequence identity thereto, CDRL2 having an amino acid sequence with sequence number 23 (WASTGES) or 90% or more sequence identity thereto, and CDRL3 having an amino acid sequence with sequence number 24 (QNAYFYPFT) or 90% or more sequence identity thereto. In certain embodiments, the anti-CLDN18.2 antibody may have two light chains, each light chain may include CDRL1 having the amino acid sequence of sequence number 22, CDRL2 having the amino acid sequence of sequence number 23, and CDRL3 having the amino acid sequence of sequence number 24.

[0656] In some embodiments, the heavy chain of the anti-CLDN18.2 antibody may include CDRH1 having an amino acid sequence having sequence identity with SEQ ID NO: 19 or 90% or more of it, CDRH2 having an amino acid sequence having sequence identity with SEQ ID NO: 20 or 90% or more of it, and CDRH3 having an amino acid sequence having sequence identity with SEQ ID NO: 21 or 90% or more of it. The light chain of the anti-CLDN18.2 antibody may include CDRL1 having an amino acid sequence having sequence identity with SEQ ID NO: 22 or 90% or more of it, CDRL2 having an amino acid sequence having sequence identity with SEQ ID NO: 23 or 90% or more of it, and CDRL3 having an amino acid sequence having sequence identity with SEQ ID NO: 24 or 90% or more of it. In certain embodiments, the anti-CLDN18.2 antibody may have two heavy chains comprising CDRH1 having the amino acid sequence of SEQ ID NO: 19, CDRH2 having the amino acid sequence of SEQ ID NO: 20, and CDRH3 having the amino acid sequence of SEQ ID NO: 21, and two light chains comprising CDRL1 having the amino acid sequence of SEQ ID NO: 22, CDRL2 having the amino acid sequence of SEQ ID NO: 23, and CDRL3 having the amino acid sequence of SEQ ID NO: 24.

[0657] In some embodiments, the anti-CLDN18.2 antibody may comprise a heavy chain having an amino acid sequence having 90% or greater sequence identity with SEQ ID NO: 25, and a light chain having an amino acid sequence having 90% or greater sequence identity with SEQ ID NO: 26. In certain embodiments, the anti-CLDN18.2 antibody may comprise a heavy chain having the amino acid sequence of SEQ ID NO: 25, and a light chain having the amino acid sequence of SEQ ID NO: 26. Specifically, the anti-CLDN18.2 antibody may comprise two heavy chains having the amino acid sequence of SEQ ID NO: 25, and two light chains having the amino acid sequence of SEQ ID NO: 26.

[0658] Linker (L'b) of an antibody conjugate containing the group of interest In the previous paragraph, it was explained in detail that, by the reaction of an antibody with a compound containing an Fc-binding unit, a portion containing the group of interest is site-specifically transferred to the antibody. The linker (linker B;L) of the antibody conjugate containing the group of interest. b ) has the same structure as a partial structure of a compound containing an Fc bond unit.

[0659] Linker B has the following structure: [ka] It may have.

[0660] In structure, R a2 , R a3 , X, and L a Each of these is described in detail in the previous paragraph, and each of them is as described in the previous paragraph.

[0661] In a particular embodiment, linker B has the following structure: [ka] It can be represented by:

[0662] In structure, R a2 , X, and L a Each of these is described in detail in the previous paragraph, and each of them is as described in the previous paragraph.

[0663] In a particular embodiment, linker B has the following structure: [ka] It can be represented by:

[0664] In the structure, X and L a Each of these is described in detail in the previous paragraph, and each of them is as described in the previous paragraph.

[0665] The part where the base of the object of interest is connected In Equation 6, n is an integer between 1 and 4. In some embodiments, n may be an integer between 1 and 2. In certain embodiments, n may be 2.

[0666] The group of interest may be linked to one or more of the lysine residues 246 (K246) and 248 (K248) of the Fc region of the antibody unit (by linker B). More specifically, the antibody unit may include two heavy chains (a first heavy chain and a second heavy chain) and "-L b -GOI may be linked to one or more of the following: K246 of the first heavy chain, K248 of the first heavy chain, K246 of the second heavy chain, and K248 of the second heavy chain.

[0667] For example, n is 1 if one group of interest is linked to K246 of the first heavy chain of the antibody unit (by linker B). For example, n is 1 if one group of interest is linked to K248 of the first heavy chain of the antibody unit.

[0668] For example, n is 2 when the two groups of interest are linked to K246 of the first heavy chain and K246 of the second heavy chain of the antibody unit, respectively. For example, n is 2 when the two groups of interest are linked to K248 of the first heavy chain and K248 of the second heavy chain of the antibody unit, respectively. For example, n is 2 when the two groups of interest are linked to K246 of the first heavy chain and K248 of the second heavy chain of the antibody unit, respectively.

[0669] For example, n is 3 when the three groups of interest are linked to K246 of the first heavy chain, K248 of the first heavy chain, and K248 of the second heavy chain of the antibody unit, respectively.

[0670] For example, if the four groups of interest are linked to K246, K248, K246, and K248 of the first heavy chain of the antibody unit, then n is 4.

[0671] Specific embodiments of antibody conjugates containing a group of interest - antibody conjugates containing a reactive group The group of interest may include a reactive group or a functional group. For example, if the group of interest includes a reactive group, an antibody conjugate containing the group of interest may be called an antibody conjugate containing a reactive group.

[0672] For example, the compound of formula 6 may be the compound of formula 6-1.

[0673] Some embodiments of this application are given by the following formula 6-1: [Formula 6-1] [ka] The present invention provides an antibody conjugate containing a group of interest having the structure of (i.e., an antibody conjugate containing a reactive group as defined herein).

[0674] At this point, L b This is linker B, and linker B is as described above.

[0675] In this case, RG is the reactive group, and the reactive group is as described above.

[0676] Use of antibody conjugates containing reactive groups Overview of the use of antibody conjugates containing reactive groups Antibody-payload conjugates (e.g., antibody-drug conjugates) may be prepared using an antibody conjugate containing a reactive group. Antibody-payload conjugates may be prepared by contacting, reacting, or mixing an antibody containing a reactive group with a payload.

[0677] An antibody conjugate containing a reactive group refers to a group that can react with other groups. For example, the reactive group may be a reactive substructure, or may contain a reactive substructure, the reactive substructure being a substructure that is reactive with other groups. For example, the reactive substructure may be a bioorthothic functional group (e.g., azide or norbornene).

[0678] The payload may contain reactive groups capable of reacting with the reactive groups of the antibody conjugate.

[0679] The reactive group in an antibody conjugate containing a reactive group may be called the first reactive group, and the reactive group in the payload may be called the second reactive group.

[0680] When an antibody conjugate containing a reactive group and a payload are contacted, reacted, or mixed, the antibody-payload conjugate may be prepared by the reaction of a first reactive group with a second reactive group.

[0681] The payload will be explained in detail from here on.

[0682] payload Payload Overview The payload may include a second reactive group and an active substructure. The payload may include one or more active substructures, each of which is independently selected. Active substructures are described in detail in the previous paragraph and are as described in the previous paragraph. For example, the active substructure may be, but is not limited to, a drug, an imaging substructure, a radioactive substructure, a protein with a specific function, a peptide with a specific function, an affinity substance (e.g., biotin, streptavidin, and aptamers), a stabilizing substance, a vitamin, a nucleic acid (e.g., DNA or RNA), or a PEG substructure. In some embodiments, the active substructure may be a drug substructure, an imaging substructure, a radioactive substructure, or an affinity substance.

[0683] The second reactant may be a group capable of reacting with the first reactant. For example, if the first reactant is an azide or contains an azide, the second reactant may be DBCO or contain DBCO capable of reacting with an azide. As another example, if the first reactant is norbornene or contains norbornene, the second reactant may be tetrazine or contain tetrazine.

[0684] In some embodiments, the sum of the atomic masses of all atoms constituting the payload may be 10,000 doltons, 9,000 doltons, 8,000 doltons, 7,000 doltons, 6,000 doltons, 5,000 doltons, 4,500 doltons, 4,000 doltons, 3,500 doltons, 3,000 doltons, 2,500 doltons, 2,000 doltons, 1,500 doltons, 1,000 doltons, or 500 doltons or less. It will be obvious to those skilled in the art that the sum of the atomic masses of all atoms belonging to the payload is 20 doltons or more.

[0685] For example, the payload is given by the following equation 7: [Formula 7] [ka] It may have a structure, In the formula, CM is the cargo substructure (CM), RG 2 This is the second reactive group.

[0686] The cargo substructure is characterized by containing one or more active substructures.

[0687] The second embodiment of the reactive group will be described below.

[0688] Second reactive group For the explanation of the second reactive group, the explanation related to the reactive group described in the "Compounds Containing Fc Bonding Units" section may be referenced.

[0689] The second reactive group includes a reactive substructure. In this case, the reactive substructure of the second reactive group is called the second reactive substructure.

[0690] In some embodiments, the second reactive group may further include a spacer for the reactive group (e.g., a spacer for the second reactive substructure) in addition to the reactive substructure (e.g., the second reactive substructure), as described in the paragraph describing the reactive group. In this case, the reactive substructure is connected to the non-reactive parts by the spacer for the reactive group. For example, the second reactive group may have the following structure: [ka] It may have, In the formula, D RG2 H is a spacer for the second reactive group. RG2 This is the second reactive substructure.

[0691] In some embodiments, the second reactive substructure may be a bioorthogonal functional group (e.g., a second bioorthogonal functional group). In this case, the description of the bioorthogonal functional group is as described in the description of bioorthogonal functional groups in the "Compounds Containing Fc Bonding Units" section of this application.

[0692] In some embodiments, the reactive substructure may be a click chemical functional group (e.g., a second click chemical functional group). In this case, the click chemical functional group is described in the description of the click chemical functional group in the “Compounds Containing Fc Bonding Units” section of this application.

[0693] In some embodiments, the reactive substructure may be selected from azide groups, terminal alkyne groups, cyclic alkyne (e.g., cyclooctin) groups, tetrazine groups, norbornene groups, cycloalkenes (e.g., cyclooctene) groups, tetrazole groups, oxime groups, and isocyanide groups, halogen groups, aldehyde groups, nitrone groups, hydroxyamine groups, nitrile groups, hydrazine groups, ketone groups, broncate groups, cyanobenzothiazole groups, allyl groups, phosphine groups, maleimide groups, disulfide groups, thioester groups, halocarbonyl groups, isonitrile groups, cydonone groups, selenium groups, thiol groups, and protected thiol groups.

[0694] Payload topology Some embodiments of the present invention provide a payload having the structure of the following formula 7-1. Some embodiments of the present invention provide a payload having the structure of the following formula 7-1: [Formula 7-1] [ka] The present invention provides a compound having the structure described herein. During the ceremony, RG 2 is the second reactive group, FG c21 FG c22 , and FG c23 These are functional group C21, functional group C22, and functional group C23, respectively. CL c21 CL c22 , and CL c23 These are respectively a cleavable linker C21, a cleavable linker C22, and a cleavable linker C23. qa is an integer between 0 and 1, qb is an integer between 0 and 1, and qc is an integer between 0 and 1. D c21 , D c22 , D c23 , D c24 , and D c25 These are spacers C21, C22, C23, C24, and C25, respectively. L c21 and L c22These are linker C21 and linker C22, respectively. 【0695...

Claims

1. Formula 2-2: [Formula 2-2] 【Chemistry 292】 Compounds containing an Fc bond unit having the structure [In the formula, D ａ is spacer A, and the spacer A is a C that is bonded, substituted or unsubstituted １～２０ alkylene, a C that is substituted or unsubstituted １～２０ heteroalkylene, a C that is substituted or unsubstituted ２～２０ alkenylene, a C that is substituted or unsubstituted ２～２０ heteroalkenylene, a C that is substituted or unsubstituted ２～２０ alkynylene, or a C that is substituted or unsubstituted ２～２０ heteroalkynylene, wherein the substituted means that one or more hydrogen atoms in a group modified by the term substituted are substituted with one or more kinds of substituents, wherein each of the substituents is independently selected from -R, =O, =S, -NO ２ , -CR ３ , -NR ２ , =NR, -OR, -SR, -C(=O)R, -C(=O)CR ３ , -C(=O)OR, and -C(=O)NR ２ selected from, wherein each of R is independently selected from H, halogen, C １～６ alkyl, C ３～１０ cycloalkyl, C ３～１０ heterocycloalkyl, aryl, heteroaryl, -OH, -NH ２ , -COOH, =O, =S, and -SH, wherein the substituent is not H, wherein heteroalkylene, heteroalkenylene, heterocycloalkyl, or heteroaryl contains one or more heteroatoms, and each of the heteroatoms is independently selected from N, O, and S L ａ Linker A is linked, substituted, or unsubstituted C １～１００ Alkylene, substituted or unsubstituted C １～１００ Heteroalkylenes, substituted or unsubstituted C ２～１００ Alkenylene, substituted or unsubstituted C ２～１００ Heteroalkenylenes, substituted or unsubstituted C ２～１００ Alkynylene, or substituted or unsubstituted C ２～１００ A heteroalkylene, where substituted means that one or more hydrogen atoms in the group modified by the term substituted are substituted with one or more types of substituents, where each of the substituents is independently -R, =O, =S, -NO ２ , -CR ３ , -NR ２ , -OR, -SR, -C(=O)R, -C(=O)CR ３ -C(=O)OR, and -C(=O)NR ２ Selected from, in the formula, each of R is independently H, halogen, C １～６ Alkyl, C ３～１０ Cycloalkyl, C ３～１０ Heterocycloalkyl, aryl, heteroaryl, -OH, -NH ２ Selected from -COOH, =O, =S, and -SH, wherein the substituent is not H, and wherein the heteroalkylene, heteroalkenylene, heteroalkylnylene, heterocycloalkyl, or heteroaryl comprises one or more heteroatoms, each of which is independently selected from N, O, and S. X is -CH ２ -, -O-, or -NH-, R ａ１ is H or C １～６ It is alkyl, R ａ２ is H or C １～６ It is alkyl, R ａ３ is H or C １～６ It is alkyl, J ａ is -C(=O)-, -S-, -NH-, or -C(=NH)-, RG is a reactive group, and the reactive group includes a reactive substructure. FcBU is an Fc coupling unit, and the Fc coupling unit is 【Chemistry 293】 It has a structure, During the ceremony, Each of Xaa is independently selected from any amino acid residue, Xa ２ This is a glutamic acid residue or an asparagine residue, Xa ３ These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. The cysteine ​​residues adjacent to the N-terminus and the cysteine ​​residues adjacent to the C-terminus are optionally linked by covalent bonds. Xa １ 'teeth 【Chemistry 294】 And, In the formula, m is an integer between 1 and 5. J ｆ is -NH-, -S-, or -C(=O)-, * and ** are each Xa １ Xa between the adjacent amino acid residues １ This represents the attachment point of ', *** is Xa, which is a portion of the compound containing the Fc bond unit that is not the Fc bond unit. １ [Represents the attachment point of '.

2. X is -O- or -CH ２ - is, A compound comprising the Fc-binding unit described in claim 1.

3. X is -O- A compound comprising the Fc-binding unit described in claim 1.

4. R ａ１ is C １～３ It is alkyl. A compound comprising the Fc-binding unit described in claim 1.

5. R ａ１ It is methyl. A compound comprising the Fc-binding unit described in claim 1.

6. R ａ２ and R ａ３ Each of these independently consists of H and C １～３ It is one of the alkyl groups selected. A compound comprising the Fc-binding unit described in claim 1.

7. R ａ２ and R ａ３ Both are H. A compound comprising the Fc-binding unit described in claim 1.

8. J ａ is -C (=O)- A compound comprising the Fc-binding unit described in claim 1.

9. D ａ is the unsubstituted C １～１０ Alkylene, unsubstituted C １～１０ heteroalkylene, unsubstituted C ２～１０ Alkenylene or unsubstituted carbon ２～１０ It is a heteroalkenylene. A compound comprising the Fc-binding unit described in claim 1.

10. D ａ is not substituted C １～１０ It is alkylene. A compound comprising the Fc-binding unit described in claim 1.

11. The Fc bond unit has the following structure: 【Chemistry 295】 Having, A compound comprising the Fc-binding unit described in claim 1.

12. J ｆ is -NH- A compound comprising the Fc-binding unit described in claim 1.

13. m is an integer between 1 and 4. A compound comprising the Fc-binding unit described in claim 1.

14. m is 3. A compound comprising the Fc-binding unit described in claim 1.

15. L ａ This is an unbonded, unsubstituted C. １～６０ Alkylene, unsubstituted C １～６０ heteroalkylene, unsubstituted C ２～６０ Alkenylene or unsubstituted carbon ２～６０ It is a heteroalkenylene. A compound comprising the Fc-binding unit described in claim 1.

16. L ａ This is an unbonded, unsubstituted C. １～６０ Alkylene or unsubstituted carbon １～６０ The heteroalkylene is an unsubstituted heteroalkylene containing 0 to 20 ethylene glycol units. A compound comprising the Fc-binding unit described in claim 1.

17. L ａ This is an unbonded, unsubstituted C. １～３０ Alkylene or unsubstituted carbon １～３０ The heteroalkylene is an unsubstituted heteroalkylene containing 0 to 10 ethylene glycol units. A compound comprising the Fc-binding unit described in claim 1.

18. L ａ This is an unbonded, unsubstituted C. １～２４ Alkylene or unsubstituted carbon １～２４ The heteroalkylene is an unsubstituted heteroalkylene containing 0 to 8 ethylene glycol units. A compound comprising the Fc-binding unit described in claim 1.

19. L ａ teeth 【Chemistry 296】 That is, Compound comprising the Fc bond unit described in claim 1 [In the formula, sf is an integer from 0 to 8. sg is an integer between 0 and 15. sh is an integer between 0 and 8.

20. sf is an integer between 0 and 3. sg is an integer between 0 and 10. sh is an integer between 0 and 3. A compound comprising the Fc-binding unit described in claim 19.

21. RG has the following structure: 【Chemistry 297】 Represented by, Compound comprising the Fc bond unit described in claim 1 [In the formula, D ＲＧ This is a spacer for the reactive group (spacer RG), The spacer of the reaction group is a bonded, substituted or unsubstituted C １～６ alkylene, substituted or unsubstituted C １～６ heteroalkylene, substituted or unsubstituted C ２～６ alkenylene, or substituted or unsubstituted C ２～６ heteroalkenylene, wherein the substituted means that one or more hydrogen atoms in the group modified by the term "substituted" are substituted with one or more kinds of substituents, and each of the substituents is independently selected from -C １～４ alkyl, -C(=O)H, -C(=O)CH ３ , -C(=O)OH, -C(=O)NH ２ , -NH ２ , =NH, =O, =S, -OH, -NO ２ , and -SH, wherein the heteroalkylene or heteroalkenylene contains one or more heteroatoms, and each of the heteroatoms is independently selected from O, N, and S H ＲＧ [This is the reactive substructure.]

22. The reactive substructure is a bioorthogonal functional group. A compound comprising the Fc-binding unit described in claim 1.

23. The reactive substructure has the following structure: 【Chemistry 298】 【Chemistry 299】 Represented by one of the following: Compound comprising the Fc bond unit described in claim 1 [In the formula, hn is an integer between 1 and 3. R Ｈ Each of which is independently selected from H or -R, =O, =S, -NO ２ , -CR ３ , -NR ２ , =NR, -OR, -SR, -C(=O)R, -C(=O)CR ３ , -C(=O)OR, and -C(=O)NR ２ and each R is independently selected from H, halogen, C １～６ alkyl, C ３～１０ cycloalkyl, C ３～１０ heterocycloalkyl, aryl, heteroaryl, -OH, -NH ２ , -COOH, =O, =S, and -SH].

24. The reactive substructure is selected from any one of the following: an azide group, a terminal alkyne group, a terminal alkene group, a cyclooctin group, a tetrazine group, a norbornene group, a cyclooctene group, an oxime group, and an isocyanide group. The cyclooctin group is selected from any one of the following: OCT cyclooctin, BCN (bicyclononine), DBCO (dibenzocyclooctin), DIBAC (aza-dibenzocyclooctin), DIBO (dibenzocyclooctinol), DIFO (difluorinated cyclooctin), BARAC (biarylazacyclooctinone), DIMAC (dimethoxyazacyclooctin), and DIFBO (difluorobenzocyclooctin). The cyclooctene group is selected from any one of the following: a cis-cyclooctene group and a trans-cyclooctene. A compound comprising the Fc-binding unit described in claim 1.

25. Formula 2-15: [Formula 2-15] 【Chemical 300】 Compounds containing an Fc bond unit having the structure [In the formula, aa is an integer between 1 and 10. X is -O- or -CH ２ - and L ａ This is linker A, and linker A is not bonded or substituted with C １～３０ Unsubstituted C, containing alkylene or 0 to 10 ethylene glycol units. １～３０ It is a heteroalkylene, 【Chemical 301】 is a reactive group, D ＲＧ This is a spacer for the reactive group (spacer RG), and the spacer for the reactive group is bonded, substituted or unsubstituted C １～６ Alkylene, substituted or unsubstituted C １～６ Heteroalkylenes, substituted or unsubstituted C ２～６ Alkenylene, or substituted or unsubstituted C ２～６ A heteroalkenylene, where substituted means that one or more hydrogen atoms in the group modified by the term substituted are substituted with one or more types of substituents, where each of the substituents is independently -C １～４ Alkyl, -C(=O)H, -C(=O)CH ３ , -C(=O)OH, -C(=O)NH ２ , -NH ２ , =NH, =O, =S, -OH, -NO ２ Selected from , and -SH, where the heteroalkylene or heteroalkenylene comprises one or more heteroatoms, each of which is independently selected from O, N, and S. H ＲＧ It is a reactive substructure, FcBU is an Fc coupling unit, and the Fc coupling unit is 【Chemical 302】 It has a structure, During the ceremony, Each of Xaa is independently selected from any amino acid residue, Xa ２ This is a glutamic acid residue or an asparagine residue, Xa ３ These are tryptophan residues, naphthylalanine residues, or phenylalanine residues. The cysteine ​​residues adjacent to the N-terminus and the cysteine ​​residues adjacent to the C-terminus are optionally linked by covalent bonds. Xa １ 'teeth 【Chemical 303】 And, In the formula, m is an integer between 1 and 4. * and ** are each Xa １ Xa with adjacent amino acid residues １ This represents the attachment point of ', *** is Xa, which is a portion of the compound containing the Fc bond unit that is not the Fc bond unit. １ [Represents the attachment point of '.

26. aa is an integer between 1 and 6. A compound comprising the Fc-binding unit described in claim 25.

27. aa is 3. A compound comprising the Fc-binding unit described in claim 25.

28. The Fc bond unit has the following structure: 【Chemical 304】 Having, A compound comprising the Fc-binding unit described in claim 25.

29. m is 3. A compound comprising the Fc-binding unit described in claim 25.

30. The reactive substructure is a bioorthogonal functional group. A compound comprising the Fc-binding unit described in claim 25.

31. The reactive substructure has the following structure: 【Chemical 305】 【Chemical 306】 Represented by one of the following: Compound comprising the Fc bond unit described in claim 25 [In the formula, hn is an integer between 1 and 3. R Ｈ Each of these is independently either H, or -R, =O, =S, or -NO. ２ , -CR ３ , -NR ２ , =NR, -OR, -SR, -C(=O)R, -C(=O)CR ３ -C(=O)OR, and -C(=O)NR ２ Selected from, where R is H, halogen, C １～６ Alkyl, C ３～１０ Cycloalkyl, C ３～１０ Heterocycloalkyl, aryl, heteroaryl, -OH, -NH ２ [Each of these can be independently selected from -COOH, =O, =S, and -SH.]

32. The reactive substructure is selected from an azide group, a terminal alkyne group, a terminal alkene group, a cyclooctin group, a tetrazine group, a norbornene group, a cyclooctene group, an oxime group, and an isocyanide group, wherein the cyclooctin group is selected from any one of OCT cyclooctin, BCN (bicyclononine), DBCO (dibenzocyclooctin), DIBAC (aza-dibenzocyclooctin), DIBO (dibenzocyclooctinol), DIFO (difluorinated cyclooctin), BARAC (biarylazacyclooctinone), DIMAC (dimethoxyazacyclooctin), and DIFBO (difluorobenzocyclooctin), and the cyclooctene group is selected from any one of a cis-cyclooctene group and a trans-cyclooctene group. A compound comprising the Fc-binding unit described in claim 25.

33. The step of contacting an antibody with a compound containing an Fc-binding unit as described in any one of claims 1 to 32. Equipped with, A method for preparing antibody conjugates containing reactive groups.

34. The aforementioned antibody is IgG. The method according to claim 33.

35. The antibody is IgG, and the IgG is human IgG, humanized IgG, or chimeric IgG. The method according to claim 33.

36. The Fc region of the antibody comprises the amino acid sequence of SEQ ID NO: 14 or an amino acid sequence having 80% or more identity thereto, and the Fc region of the antibody comprises the amino acid sequence of KPKDTLM (SEQ ID NO: 10) and the amino acid sequence of MHEALHNHY (SEQ ID NO: 12). The method according to claim 33.

37. In the step of contacting the compound containing the Fc binding unit with the antibody, the reactive group is moved to the target region of the antibody. The target region consists of five consecutive amino acid residues, including K246 and K248 of the Fc region of the antibody. The method according to claim 33.

38. In the step of contacting the compound containing the Fc binding unit with the antibody, the reactive group is moved to one or more of K246 and K248 in the Fc region of the antibody. The method according to claim 33.

39. The step of obtaining an antibody conjugate containing the aforementioned reactive group further comprises the step of obtaining an antibody conjugate containing the aforementioned reactive group. The method according to claim 33.

40. An antibody conjugate containing the reactive group is prepared by contacting the compound containing the Fc binding unit with the antibody. The antibody conjugate containing the aforementioned reactive groups contains 1 to 4 reactive groups. The method according to claim 33.

41. An antibody conjugate containing the reactive group is prepared by contacting the compound containing the Fc binding unit with the antibody. The antibody conjugate containing the aforementioned reactive group contains two reactive groups, In the antibody conjugate containing the reactant, one of the two reactants (the first reactant) is linked to one of K246 and K248 of one of the two heavy chains of the antibody (the first heavy chain), In an antibody conjugate containing the aforementioned reactive group, the other reactive group of the two reactive groups (the second reactive group) is linked to one of K246 and K248 of the other heavy chain (the second heavy chain) of the two heavy chains of the antibody. The method according to claim 33.

42. An antibody conjugate containing the reactive group is prepared by contacting the compound containing the Fc binding unit with the antibody. The antibody conjugate containing the aforementioned reactive group contains two reactive groups, Each of the two reactive groups is linked to K246 of one heavy chain of the antibody and K246 of the other heavy chain of the antibody, respectively, or linked to K248 of one heavy chain of the antibody and K248 of the other heavy chain of the antibody, respectively. The method according to claim 33.

43. The step of contacting the compound containing the Fc binding unit with the antibody is as follows: A step of mixing a composition having the compound containing the Fc binding unit with a composition containing the antibody. Achieved by a method comprising, The method according to claim 33.

44. The step of mixing the composition having the compound containing the Fc binding unit with the composition containing the antibody is performed under conditions of pH 6 to pH 8.

5. The method according to claim 43.

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