Bifunctional degradants for galactose-deficient immunoglobulins.

Abstract

An agent comprising a glycan-specific IgG antibody portion, a cell receptor binding portion that binds to hepatocytes or other degraded cells via a hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor on the surface of the degraded cells of a patient or subject, and optionally a linker portion connecting the glycan-specific IgG antibody portion and the cell receptor binding portion.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 159,383, filed March 10, 2021, and any and all benefits arising therefrom under 35 U.S.C. § 119, the contents of which are incorporated herein by reference in their entirety.

[0002] The present invention relates to bifunctional molecules containing a circulating protein-binding moiety linked to a cell receptor-binding moiety via a linker group. Specifically, the present invention relates to bifunctional molecules containing a circulating protein-binding moiety that binds to galactose-deficient immunoglobulins. [Background technology]

[0003] IgA nephropathy (IgAN) is an autoimmune disease characterized by circulating nephritogenic immune complexes composed of galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG antibodies. These immune complexes accumulate in the glomerular mesangium and induce the mesangioproliferative glomerulonephritis characteristic of IgAN, which is responsible for renal damage. This hypothesis is supported by the finding that IgG is enriched for Gd-IgA1-specific antibodies in renal immune deposits in patients with IgA neuropathy. Furthermore, serum levels of Gd-IgA1 (an autoantigen) and the corresponding autoantibodies have been found to correlate with the severity and progression of IgAN, respectively. Suzuki et al., “Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity,” J. Clin. Invest. 2009, 119(6), 1668-1677 (Appendix A), incorporated herein by reference in its entirety.

[0004] A recent study provided in vivo evidence for the nephritogenic role of IgG autoantibodies in IgAN. This study showed that immune complexes formed from human IgG autoantibodies and Gd-IgA1 injected intravenously into mice caused glomerular injury. The histopathological changes in the damaged tissue were characteristic of IgAN. Exploratory kidney-transcriptome profiling showed that these immune complexes altered gene expression in multiple pathways consistent with changes observed in kidney biopsies from patients with IgAN. Moldoveanu et al., "Experimental evidence of pathogenic role of IgG autoantibodies in IgG nephropathy," J. Autoimmun. 2021, 118, 102593 (Appendix B), incorporated herein by reference in its entirety.

[0005] IgAN is the most common form of primary glomerulonephritis worldwide for which there is currently no cure. Therefore, there remains a need for new medicines that can treat the disease or slow its progression. Summary of the Invention

[0006] The present invention is directed to bifunctional molecules that are capable of binding and degrading galactose-deficient immunoglobulins.

[0007] In one embodiment, the drug is a glycan-specific IgG antibody portion; a cell receptor binding moiety that binds to hepatocytes or other lysed cells via the hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor on the surface of lysed cells in a patient or subject; Optionally, an agent is provided that includes a linker moiety connecting the glycan-specific IgG antibody moiety and the cell receptor binding moiety.

[0008] In another embodiment, a method is provided for removing galactosyl IgA1 in a patient or subject in need thereof by administering an agent to the mammal.

[0009] In another embodiment, a method is provided for treating a disease state and / or condition associated with upregulation of galactosyl IgA1 in a patient or subject in need thereof by administering an effective amount of an agent to the mammal.

[0010] In another embodiment, a composition is provided that includes a drug and at least one additional drug that includes a moiety that can bind to an antibody that forms the antibody portion of the first compound. DETAILED DESCRIPTION OF THE INVENTION

[0011] The following detailed description is provided to assist those skilled in the art in practicing the present invention. Exemplary embodiments are described in detail hereinafter. However, these embodiments are exemplary only, and the disclosure is not limited thereto, but rather is defined by the scope of the appended claims. Those skilled in the art may make modifications and variations in the embodiments described herein without departing from the spirit or scope of the disclosure.

[0012] Accordingly, embodiments are described below merely by reference to structures and schemes to illustrate aspects of the specification. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. The term "or" means "and / or." Phrases such as "at least one of" preceding a list of elements modify the entire list of elements, and not individual elements of the list.

[0013] When an element is referred to as being "on" another element, it will be understood that it may be in direct contact with the other element, or there may be intervening elements between them. In contrast, when an element is referred to as being "directly on" another element, there are no intervening elements present.

[0014] Terms such as first, second, and third may be used herein to describe various elements, components, regions, layers, and / or sections, but it should be understood that these elements, components, regions, layers, and / or sections should not be limited by these terms. These terms are used only to distinguish one element, component, region, layer, or section from another element, component, region, layer, or section. Thus, a first element, component, region, layer, or section discussed below could be referred to as a second element, component, region, layer, or section without departing from the teachings of the present embodiments.

[0015] As used herein, the terms "comprises" and / or "comprising" or "includes" and / or "including" specify the presence of stated features, regions, integers, steps, operations, elements, and / or components, but are to be understood as not excluding the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and / or groups thereof.

[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used herein is intended only to describe particular embodiments and is not intended to be limiting. Terms, such as those defined in commonly used dictionaries, should be interpreted to have a meaning consistent with their meaning in the relevant technical field and in the context of this disclosure, and should not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0017] As used in this application, except as expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout this application. If a term is not specifically defined herein, the term will be given the art-recognized meaning by those of ordinary skill in the art applying the term in connection with its use in describing the present invention.

[0018] The articles "a" and "an" refer to one or to more than one (i.e., to at least one) of the grammatical object of the article, unless the context clearly dictates otherwise. By way of example, "an element" means one element or more than one element.

[0019] Additional aspects are set forth in part in the description that follows, and in part will be apparent from the description.

[0020] In one embodiment, the drug is an antibody binding moiety; a cell receptor binding moiety that binds to hepatocytes or other lysed cells via the hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor on the surface of lysed cells in a patient or subject; Optionally, an agent is provided that includes a linker moiety connecting the antibody moiety and the cell receptor binding moiety.

[0021] The antibody-binding moiety may be a glycan-specific IgG antibody moiety. The glycan-specific IgG antibody moiety may be configured to bind to galactose-deficient IgA1 (Gd-IgA1). In certain embodiments, the glycan-specific IgG antibody moiety may be a recombinant IgG antibody moiety (rIgG). In other embodiments, the glycan-specific IgG antibody moiety may be isolated from the serum of a patient with IgA nephropathy.

[0022] The presently claimed bifunctional compounds selectively bind to circulating galactose-deficient IgA1, forming a protein complex that then binds to a cellular receptor, is endocytosed, and degraded. As a result of this mechanism, galactose-deficient IgA1 is removed from the circulation by hepatocytes, macrophages, or other cell types, thus reducing the level of galactose-deficient IgA1 and potentially alleviating IgAN symptoms. In certain cases, galactose-deficient IgA1 may be removed, resulting in a substantial reduction, or even cure or elimination, of the symptoms of IgAN.

[0023] In some embodiments, the present disclosure provides: R CN -(Xaa)yR CC , [ka] , [ka] , [ka] , or [ka] or a salt thereof. In some embodiments, the agent has the structure: [ka] or a salt thereof. In some embodiments, the agent has the structure: [ka] or a salt thereof. In some embodiments, the agent has the structure: [ka] or a salt thereof. In some embodiments, the agent has the structure: [ka] In some embodiments, each cell receptor binding moiety independently has the structure -(R CN -(Xaa)yR CC ), or a salt form thereof. In the above structure, a, b, and c may independently be integers greater than or equal to 1.

[0024] In some embodiments, the antibody binding moiety is a universal antibody binding moiety.

[0025] In some embodiments, an antibody binding moiety comprises one or more amino acid residues. In some embodiments, an antibody binding moiety is or comprises a peptide moiety. In some embodiments, an antibody binding moiety is or comprises a cyclic peptide moiety. In some embodiments, such an antibody binding moiety comprises one or more naturally occurring amino acid residues. In some embodiments, such an antibody binding moiety comprises one or more non-naturally occurring amino acid residues.

[0026] In some embodiments, the antibody binding moiety is a cyclic peptide moiety. In some embodiments, the antibody binding moiety is [ka] or a salt form thereof. In some embodiments, the antibody binding moiety is or comprises: [ka] or a salt form thereof. In some embodiments, each antibody binding moiety in the agent is independently: [ka] or a salt form thereof. In some embodiments, each antibody binding moiety in the agent is independently [ka] or a salt form thereof. In some embodiments, each antibody binding moiety in the agent is of the same antibody binding moiety or salt thereof.

[0027] In some embodiments, the present disclosure provides a compound of formula Ia: [ka] Ia or a salt thereof, wherein: each Xaa is independently a residue of an amino acid or amino acid analog; t is 0 to 50; z is 1 to 50; L is a linker moiety, TBT is the cell receptor binding moiety, Each R c independently, -L a -R', each of a and b independently represents 1 to 200; Each L a are independently a covalent bond or C1 to C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3~20 Alicyclic ring, C 6~20an aryl ring, a 5-20 membered heteroaryl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1~30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1~30 Heteroaliphatic, C 6~30 Aryl, C 6~30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6~30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Provided is a compound or salt thereof, wherein two or more R groups on two or more atoms optionally and independently, together with their intervening atoms, form an optionally substituted 3- to 30-membered monocyclic, bicyclic, or polycyclic ring having, in addition to the intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0028] In some embodiments, a is 1. In some embodiments, b is 3. In some embodiments, a is 1 and b is 3, and the compound of formula Ia is [ka] It has the following structure.

[0029] In some embodiments, each residue, eg, Xaa, is independently a residue of an amino acid or amino acid analog, and the amino acid or amino acid analog is HL a1 -L a1 -C(R a2 )(R a3 )-L a2 -L a2 In some embodiments, the amino acid has the structure NH(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 In some embodiments, the amino acid analog has the structure HL a1 -L a1 -C(R a2 )(R a3 )-L a2 -L a2 In some embodiments, such amino acid analogs have the structure -H, or a salt thereof. a1 - (bonded to -H in the formula) is -N(R a1 )- (e.g., optionally substituted divalent C 1~6 In some embodiments, HL a1 -L a1 -In -L a1 -L a1 - is attached to -H through a non-nitrogen atom. a2 -L a2 In -H, -L a2 -L a2 - is not attached to -H through -C(O)O-. In some embodiments, each residue (e.g., each Xaa in Formula Ia) is independently a residue of an amino acid having the structure of Formula AI.

[0030] In some embodiments, each Xaa is independently -L a1 -L a1 -C(R a2 )(R a3 )-L a2 -L a2 In some embodiments, each Xaa independently has the structure -L aX1 -L a1 -C(R a2 )(R a3 )-L a2 -L aX2 -having the structure of L aX1 is an optionally substituted —NH—, an optionally substituted —CH—, —N(R a1 )- or -S-, and L aX2 is an optionally substituted —NH—, an optionally substituted —CH—, —N(R a1 )-, or -S-, and each other variable is independently as described herein. aX1 is an optionally substituted —NH— or —N(R a1 In some embodiments, L aX1 is optionally substituted —CH— or —S—. In some embodiments, L aX2 is an optionally substituted —NH—, an optionally substituted —CH—, —N(R a1 )-, or -S-. In some embodiments, the optionally substituted -CH2- is -C(O)-. In some embodiments, the optionally substituted -CH2- is not -C(O)-. In some embodiments, L aX2 In some embodiments, each Xaa is independently -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 It has the structure -CO-.

[0031] In many embodiments, two or more residues (e.g., two or more Xaa residues) are linked together to form one or more ring structures. The residues may optionally be joined at any suitable position with a linker (e.g., L T ) of an amino acid residue in a compound of Formula Ia. a2 or R a3 and another amino acid residue R a2 or R a3 ) optionally form a bridge together, for example, in some embodiments, two cysteine ​​residues form a -SS- bridge, as typically observed in natural proteins. In some embodiments, the bridge formed is b It has the structure of L b is, as described in this disclosure, L a In some embodiments, L b each end independently connects to a backbone atom of the cyclic peptide (e.g., -(Xaa) of Formula Ia) z -) to a ring atom of the ring formed by L b contains an R group (e.g., L b where a methylene unit of is replaced by -C(R)2- or -N(R)-, the R group is an R group attached to a backbone atom (e.g., R a1 , R a2 , R a3 and the like, when R) together with their intervening atoms form a ring. b is connected to the ring (e.g., -(Xaa) in Formula Ia) via the side chain of the amino acid residue (e.g., Xaa in Formula Ia) z In some embodiments, such side chains include amino groups or carboxylic acid groups. In some embodiments, L T is the L described herein b In some embodiments, the linkage (e.g., L b or L T) connects a side chain to the N-terminus or C-terminus of a residue. In some embodiments, a linkage connects a side chain to an amino group of a residue. In some embodiments, a linkage connects a side chain to an alpha-amino group of a residue. In some embodiments, a linkage (e.g., L) connects a side chain to the N-terminus or C-terminus of a residue, as shown herein. b or L T ) is -CH2-C(O)-. In some embodiments, -CH2- is attached to a side chain (e.g., attached to the -S- of a cysteine ​​residue) and -C(O)- is attached to an amino group (e.g., the alpha-amino group of a residue). In some embodiments, the linkage (e.g., L b or L T ) is an optionally substituted —CH—S—CH—C(O)—NH—, where each terminus is attached to the alpha carbon of the residue. In some embodiments, —NH— is in the alpha-amino group of the residue (e.g., the alpha-amino group of the N-terminal residue).

[0032] In some embodiments, [ka] is the antibody binding moiety ( [ka] binds to the antibody). In some embodiments, [ka] is a universal antibody binding moiety. In some embodiments, [ka] is a universal antibody binding moiety and can bind to antibodies with different Fab regions. [ka] is a universal antibody binding moiety and is capable of binding to the Fc region. In some embodiments, the antibody binding moiety (e.g., [ka] In some embodiments, the antibody binding moiety (e.g., a universal antibody binding moiety having the structure [ka] The antibody binding portion has the structure [ka] In some embodiments, [ka] teeth, [ka] It has the following structure.

[0033] In certain embodiments, the present disclosure provides a compound of formula II: [ka] II or a pharmaceutically acceptable salt thereof, wherein: R 1 , R 3 , and R 5 Each of is independently hydrogen or C 1~6 an optionally substituted group selected from an aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocycle, a phenyl, an 8-10 membered bicyclic aromatic carbocycle, a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1 and R 1’optionally, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 3 and R 3’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R attached to the same carbon atom 5 Groups and R 5’ groups optionally taken together with their intervening carbon atoms form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocyclic ring or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or The Two R's 5 The groups, optionally together with their intervening atoms, are C 1~10 wherein 1 to 3 methylene units of the chain are independently and optionally selected from -S-, -SS-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, or -Cy 1 - and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1’ , R 3’ , and R 5’ Each of is independently hydrogen or an optionally substituted C 1~3 is aliphatic, R 2 , R 4, and R 6 Each of is independently hydrogen or an optionally substituted C 1~4 aliphatic or R 2 and R 1 optionally taken together with their intervening atoms, form an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 4 and R 3 optionally together with their intervening atoms form a 4-8 membered, optionally substituted, saturated or partially unsaturated, monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or R 6 group and its adjacent R 5 groups optionally taken together with their intervening atoms form an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; L 1 teeth, [ka] and [ka] is a trivalent linker moiety connecting L 2 is a covalent bond or C 1~30 wherein 1 to 10 methylene units of the chain are independently and optionally selected from -S-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, -(CHOCH2)n-, -(OCH2CH2)n-, or -Cy 1 - and each -Cy 1- is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBT is the cell receptor binding moiety, Each of m and n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or a pharmaceutically acceptable salt thereof.

[0034] In some embodiments, the amino acid has the formula AI: NH(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 -COOH, AI or a salt thereof, wherein: R a1 , R a2 , R a3 each independently represents -L a -R', L a1 and L a2 Each of the a and Each L a are independently a covalent bond or C1 to C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3~20 Alicyclic ring, C 6~20an aryl ring, a 5-20 membered heteroaryl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1~30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1~30 Heteroaliphatic, C 6~30 Aryl, C 6~30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6~30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0035] In some embodiments, the residue is -N(R a1 )-L a1 -C(Ra2 )(R a3 )-L a2 It has the structure -COO- or a salt thereof.

[0036] In some embodiments, amino acid analogs are compounds in which the amino group and / or carboxylic acid group are independently replaced with an optionally substituted aliphatic or heteroaliphatic moiety. As will be understood by those skilled in the art, many amino acid analogs that mimic the structure, properties, and / or function of amino acids have been described in the art and can be utilized in accordance with the present disclosure, for example, for various moieties. In some embodiments, one or more peptide groups are optionally and independently replaced with a non-peptide group. In some embodiments, an amino acid moiety in a polypeptide or peptide is replaced with an amino acid analog moiety.

[0037] MATE In some embodiments, the present disclosure provides a medicament comprising: an antibody portion; and a cell receptor binding portion; Optionally, a linker moiety connecting the antibody moiety and the cell receptor binding moiety is provided.

[0038] Such agents may be referred to as MATE agents or MATEs. MATE agents are described, for example, in International Application No. PCT / US2020 / 061127, filed November 18, 2020, and U.S. Provisional Patent Application No. 63 / 146584, filed February 6, 2021, the contents of each of which are incorporated herein by reference in their entirety. In some embodiments, the agent includes an antibody portion, a cell receptor binding portion, and a linker portion connecting the antibody portion and the cell receptor binding portion.

[0039] The antibody-binding moiety may be a glycan-specific IgG antibody moiety. The glycan-specific IgG antibody moiety may be configured to bind to galactose-deficient IgA1 (Gd-IgA1). In certain embodiments, the glycan-specific IgG antibody moiety may be a recombinant IgG antibody moiety (rIgG). In other embodiments, the glycan-specific IgG antibody moiety may be isolated from the serum of a patient with IgA nephropathy.

[0040] In some embodiments, the agent has the formula MI: [ka] MI or a pharmaceutically acceptable salt thereof, wherein each of a, b, and c independently represents 1 to 200; each AT is independently an antibody moiety; L is a linker moiety, Each TBT is independently a cell receptor binding moiety.

[0041] In some embodiments, the agent has formula M-II: [ka] M-II or a pharmaceutically acceptable salt thereof, wherein each of a and b independently represents 1 to 200; each AT is independently an antibody moiety; L is a linker moiety, Each TBT is independently a cell receptor binding moiety.

[0042] In some embodiments, the agent comprises one and no more than one antibody moiety. In some embodiments, one or no more than one antibody moiety is attached to a linker moiety. In some embodiments, a is 1. In some embodiments, the agent comprises two or more antibody moieties. In some embodiments, two or more antibody moieties are attached to a single linker moiety. In some embodiments, a is 2 or more. In some embodiments, one and no more than one cell receptor binding moiety is attached to a linker moiety. In some embodiments, b is 1. In some embodiments, two or more cell receptor binding moieties are attached to a single linker moiety. In some embodiments, b is 2 or more. In some embodiments, the agent comprises one and no more than one cell receptor binding moiety. In some embodiments, c is 1. In some embodiments, b is 1 and c is 1. In some embodiments, a is 1, b is 1 and c is 1. In some embodiments, the agent comprises two or more target binding moieties. In some embodiments, b is 2 or more and c is 1. In some embodiments, b is 2 or more and c is 2 or more. In some embodiments, b is 1 and c is 2 or greater.

[0043] In some embodiments, c is 1 to 20, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, c is 1 to 15. In some embodiments, c is 1 to 10. In some embodiments, c is 1 to 9. In some embodiments, c is 1 to 8. In some embodiments, c is 1 to 7. In some embodiments, c is 1 to 6. In some embodiments, c is 1 to 5. In some embodiments, c is 1 to 4. In some embodiments, c is 1 to 3. In some embodiments, c is 1 to 2. In some embodiments, c is 1. In some embodiments, c is 2. In some embodiments, c is 3. In some embodiments, c is 4. In some embodiments, c is 5. In some embodiments, c is 6. In some embodiments, c is 7. In some embodiments, c is 8. In some embodiments, c is 9.

[0044] In some embodiments, each cell receptor binding moiety in the agent is the same. In some embodiments, each linker moiety connecting the cell receptor binding moiety to the antibody moiety is the same. In some embodiments, the TBT in the agent is the same. In some embodiments, -L-(TBT) b are the same.

[0045] In some embodiments, b is 1. In some embodiments, c is 1. In some embodiments, c is 2 or greater. In some embodiments, c is 2. Those of skill in the art will appreciate that various techniques can be used to conjugate an antibody moiety to a target-binding moiety in accordance with the present disclosure (e.g., particular techniques used to prepare antibody-drug conjugates). In some embodiments, the target-binding moiety is connected to the antibody moiety via a particular type of group and / or amino acid residue. For example, in some embodiments, the target-binding moiety is connected to a lysine residue, optionally via a linker moiety. In some embodiments, the target-binding moiety is connected to a cysteine ​​residue, optionally via a linker moiety. In some embodiments, the target-binding moiety is connected to a non-natural amino acid residue, optionally via a linker moiety. In some embodiments, the present disclosure provides techniques for selectively linking a target-binding moiety to a particular amino acid residue, optionally via a linker moiety. In some embodiments, the provided techniques selectively connect the target-binding moiety to a particular type of amino acid residue (e.g., a lysine residue), optionally via a linker moiety. In some embodiments, the provided techniques selectively connect the target-binding moiety to a particular site on the antibody moiety, optionally via a linker moiety. In some embodiments, the provided technology selectively connects the target-binding moiety to a specific type of amino acid residue at a specific site, optionally via a linker moiety. For example, in some embodiments, the target-binding moiety is connected to K246 and K248 of an IgG1 heavy chain and corresponding amino acid residues, optionally via a linker moiety. For example, in some embodiments, the target-binding moiety is connected to K251 and K253 of an IgG2 heavy chain and corresponding amino acid residues, optionally via a linker moiety. For example, in some embodiments, the target-binding moiety is connected to K239 and K241 of an IgG4 heavy chain and corresponding amino acid residues, optionally via a linker moiety. In some embodiments, the cell receptor-binding moiety is connected to a specific amino acid residue or site, optionally via a linker moiety.In some embodiments, each cell receptor binding moiety is independently connected, optionally via a linker, to a specific amino acid residue or site. As will be appreciated by those skilled in the art, an antibody drug may contain more than one specific site (e.g., one on each of more than one chain (e.g., one or each heavy chain)). In some embodiments, the antibody moiety comprises two heavy chains, and one or both of the amino acid residues or their corresponding amino acid residues are each independently connected, optionally via a linker, to a cell receptor binding moiety. In some embodiments, one and less than one are connected. In some embodiments, c is 1. In some embodiments, both are connected. In some embodiments, c is 2. In some embodiments, both target binding moieties and / or both linker moieties (if present) are the same.

[0046] antibody binding part A variety of antibody binding moieties, including universal antibody binding moieties, can be utilized in accordance with the present disclosure. Specific antibody binding moieties, as well as techniques for identifying and / or evaluating antibody binding moieties, are described in WO2019 / 023501 and WO2019 / 136442, each of which is incorporated herein by reference in its entirety. Those skilled in the art will appreciate that additional techniques in the art may be suitable for identifying and / or evaluating antibody binding moieties in accordance with the present disclosure. In some embodiments, the antibody binding moieties each independently comprise one or more amino acid residues that are natural or non-natural.

[0047] In some embodiments, the antibody binding moiety, e.g., protein binding moiety (e.g., antibody binding moiety (e.g., universal antibody binding moiety)), is [ka] or a salt thereof, wherein: R 1 , R 3 , and R 5 Each of is independently hydrogen or C 1~6an optionally substituted group selected from an aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocycle, a phenyl, an 8-10 membered bicyclic aromatic carbocycle, a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1 and R 1’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 3 and R 3’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R attached to the same carbon atom 5 Groups and R 5’ groups optionally taken together with their intervening carbon atoms form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocyclic ring or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or The Two R's 5 The groups, optionally together with their intervening atoms, are C 1~10wherein 1 to 3 methylene units of the chain are independently and optionally selected from -S-, -SS-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, or -Cy 1 - and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1’ , R 3’ , and R 5’ Each of is independently hydrogen or an optionally substituted C 1~3 is aliphatic, R 2 , R 4 , and R 6 Each of is independently hydrogen or an optionally substituted C 1~4 aliphatic or R 2 and R 1 optionally taken together with their intervening atoms, form an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 4 and R 3 optionally together with their intervening atoms form a 4-8 membered, optionally substituted, saturated or partially unsaturated, monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or R 6 group and its adjacent R 5 groups optionally taken together with their intervening atoms form an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; L 1 is a trivalent linker moiety, Each of m and n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

[0048] In some embodiments, L 1 is C1~C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced with -C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L 1 is -(CH2CH2O) 2~4 - or -(CH2CH2O)2-.

[0049] In some embodiments, the antibody binding moiety, e.g., protein binding moiety (e.g., antibody binding moiety (e.g., universal antibody binding moiety)), is [ka] or a salt thereof, wherein: R 7 Each of is independently hydrogen or C 1~6 an optionally substituted group selected from an aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocycle, a phenyl, an 8-10 membered bicyclic aromatic carbocycle, a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R attached to the same carbon atom7 Groups and R 7’ groups optionally taken together with their intervening carbon atoms form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocyclic ring or a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 7’ each independently represents hydrogen or an optionally substituted C 1~3 is aliphatic, R 8 each independently represents hydrogen or an optionally substituted C 1~4 aliphatic or R 8 group and its adjacent R 7 groups optionally taken together with their intervening atoms form an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 9 is hydrogen or an optionally substituted C 1~3 It is aliphatic, or -C(O)-.

[0050] In some embodiments, the antibody binding moiety, e.g., the universal antibody binding moiety, can be a peptide moiety (e.g., R c -(Xaa)z-) or a salt form thereof, wherein R c Each of Xaa, z, and Xaa is independently as described herein. In some embodiments, one or more Xaa is independently a non-natural amino acid residue. In some embodiments, the side chains of two or more amino acid residues may be linked together to form a bridge. For example, in some embodiments, the side chains of two cysteine ​​residues may form a disulfide bridge containing -SS- (which may be formed by two -SH groups, as in many proteins).

[0051] In some embodiments, the antibody binding moiety, e.g., protein binding moiety (e.g., antibody binding moiety (e.g., universal antibody binding moiety)), is a cyclic peptide moiety, e.g., [ka] or a salt form thereof, wherein each Xaa is independently a residue of an amino acid or amino acid analog; t is 0 to 50; z is 1 to 50; Each R c independently, -L a -R', Each L a are independently a covalent bond or C1 to C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3~20 Alicyclic ring, C 6~20 an aryl ring, a 5-20 membered heteroaryl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1~30Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1~30 Heteroaliphatic, C 6~30 Aryl, C 6~30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6~30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms may optionally and independently be joined together with their intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to the intervening atoms, 0-10 heteroatoms.

[0052] In some embodiments, the heteroatoms are independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0053] In some embodiments, the antibody binding moiety is R c In some embodiments, the protein-binding moiety is or includes -(Xaa)z-, or a salt form thereof, wherein each variable is as described herein. c In some embodiments, the antibody binding moiety, e.g., the universal antibody binding moiety, is or comprises R cIn some embodiments, the antibody binding moiety is or comprises -(Xaa)z-, or a salt form thereof, wherein each variable is as described herein. [ka] or a salt form thereof, wherein each variable is as described herein. In some embodiments, the protein binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety, e.g., a universal antibody binding moiety, is or comprises: [ka] or a salt form thereof, wherein each variable is as described herein. In some embodiments, the antibody binding moiety, e.g., the universal antibody binding moiety, is or comprises R c -(Xaa)z- or [ka] or a salt form thereof, and is or comprises a peptide unit. In some embodiments, -(Xaa)z- is or comprises a peptide unit. In some embodiments, amino acid residues may form bridges, e.g., linkages formed by side chains, optionally via a linker moiety (e.g., L); for example, as in many polypeptides, cysteine ​​residues may form disulfide bridges. In some embodiments, a peptide unit is an amino acid residue (e.g., a "positively charged amino acid residue" at physiological pH about 7.4, Xaa P), e.g., a residue of an amino acid of formula AI having a positively charged side chain. In some embodiments, the peptide unit comprises R. In some embodiments, at least one Xaa is R. In some embodiments, the peptide unit is or comprises APAR. In some embodiments, the peptide unit is or comprises RAPA. In some embodiments, the peptide unit is a hydroxyl group-containing amino acid residue ("aromatic amino acid residue", Xaa A ) (e.g., residues of amino acids of formula AI). In some embodiments, the peptide unit comprises a positively charged amino acid residue and an aromatic amino acid residue. In some embodiments, the peptide unit comprises W. In some embodiments, the peptide unit comprises a positively charged amino acid residue and an aromatic amino acid residue. In some embodiments, the peptide unit comprises a Xaa A XaaXaa P Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa P XaaXaa A In some embodiments, the peptide unit is or comprises Xaa P Xaa A Xaa P In some embodiments, the peptide unit is or comprises two or more Xaa P Xaa A Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa A Xaa P XaaXaa P Xaa A Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa P Xaa A Xaa A Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa P Xaa P XaaA In some embodiments, the peptide unit is or comprises two or more Xaa A Xaa A Xaa P In some embodiments, the peptide unit is or comprises HWRGWA. In some embodiments, the peptide unit is or comprises WGRR. In some embodiments, the peptide unit is or comprises RRGW. In some embodiments, the peptide unit is or comprises NKFRGKYK. In some embodiments, the peptide unit is or comprises NRFRGKYK. In some embodiments, the peptide unit is or comprises NARKFYK. In some embodiments, the peptide unit is or comprises NARKFYKG. In some embodiments, the peptide unit is or comprises HWRGWV. In some embodiments, the peptide unit is or comprises KHFRNKD. In some embodiments, the peptide unit is or comprises positively charged amino acid residues, aromatic amino acid residues, and amino acid residues, for example, residues of amino acids of formula AI having negatively charged side chains (e.g., "negatively charged amino acid residues" at physiological pH of about 7.4, Xaa N). In some embodiments, the peptide unit comprises RHRFNKD. In some embodiments, the peptide unit is RHRFNKD. In some embodiments, the peptide unit comprises TY. In some embodiments, the peptide unit is TY. In some embodiments, the peptide unit comprises TYK. In some embodiments, the peptide unit is TYK. In some embodiments, the peptide unit comprises RTY. In some embodiments, the peptide unit is RTY. In some embodiments, the peptide unit comprises RTYK. In some embodiments, the peptide unit is RTYK. In some embodiments, the peptide unit is or comprises a sequence selected from PAM. In some embodiments, the peptide unit comprises WHL. In some embodiments, the peptide unit is WHL. In some embodiments, the peptide unit is or comprises WXL, where X is an amino acid residue described herein, e.g., an amino acid residue including -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit comprises WDL. In some embodiments, the peptide unit is WDL. In some embodiments, the peptide unit comprises ELVW. In some embodiments, the peptide unit is ELVW. In some embodiments, the peptide unit comprises GELVW. In some embodiments, the peptide unit is GELVW. In some embodiments, the peptide unit is or comprises a sequence selected from AWHLGELVW. In some embodiments, the peptide unit is or comprises AWHLGELVW. In some embodiments, the peptide unit is or comprises a sequence selected from AWDLGELVW. In some embodiments, the peptide unit is or comprises AWDLGELVW. In some embodiments, the peptide unit is or comprises AWXLGELVW, where X is an amino acid residue described herein, e.g., one suitable for connection to another moiety (e.g., an amino acid residue including -COOH, or a salt or activated form thereof, e.g., D, E, etc.).In some embodiments, the peptide unit is or comprises a sequence selected from DCAWHLGELVWCT, where the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. In some embodiments, the peptide unit is or comprises a sequence selected from DCAWHLGELVWCT, where the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. In some embodiments, the peptide unit is or comprises a sequence selected from DCAWXLGELVWCT, where the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins, and X is an amino acid residue described herein, e.g., one suitable for connection to another moiety (e.g., an amino acid residue including -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is or comprises DCAWXLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins, and X is an amino acid residue described herein, e.g., one suitable for connection to another moiety (e.g., an amino acid residue comprising -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, X comprises -COOH, or a salt or activated form thereof, in its side chain. In some embodiments, the peptide unit is or comprises a sequence selected from DCAWDLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. In some embodiments, the peptide unit is or comprises a sequence selected from Fc-III. In some embodiments, the peptide unit is or comprises Fc-III. In some embodiments, the peptide unit is. D P LPAWXLGELVW, where X is an amino acid residue described herein, e.g., one suitable for attachment to another moiety (e.g., an amino acid residue containing -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is: D P L PAWXLGELVW, where X is or comprises an amino acid residue described herein, e.g., one suitable for attachment to another moiety (e.g., an amino acid residue including -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is: D P L In some embodiments, the peptide unit is or comprises a sequence selected from: D P L In some embodiments, the peptide unit is or comprises: D P L In some embodiments, the peptide unit is or comprises a sequence selected from: PAWHLGELVW, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. D P L In some embodiments, the peptide unit is or comprises a sequence selected from FcBP-1, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in the native protein. In some embodiments, the peptide unit is or comprises a sequence selected from FcBP-1. In some embodiments, the peptide unit is D P L PDCAWXLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins, and X is an amino acid residue described herein, e.g., one suitable for attachment to another moiety (e.g., an amino acid residue containing -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is D P LPDCAWXLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins, and X is an amino acid residue described herein, e.g., one suitable for attachment to another moiety (e.g., an amino acid residue containing -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is: D P L In some embodiments, the peptide unit is or comprises a sequence selected from: PDCAWHLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. D P L In some embodiments, the peptide unit is or comprises: PDCAWHLGELVWCT (e.g., FcBP-2), wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. D P L PDCAWDLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. D P L In some embodiments, the peptide unit is or comprises a sequence selected from FcBP-2, CDCAWXLGELVWCT, and the two cysteine ​​residues are capable of forming a disulfide bond as found in the naturally occurring protein. In some embodiments, the peptide unit is or comprises a sequence selected from CDCAWXLGELVWCTC, and the first and last cysteines and the two cysteines in the middle of the sequence are each independently selected from the naturally occurring protein. In some embodiments, the peptide unit is or comprises a sequence selected from CDCAWXLGELVWCTC, wherein the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a naturally occurring protein, and X is an amino acid residue described herein, e.g., one suitable for connection to another moiety (e.g., an amino acid residue containing -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is or comprises a sequence selected from CDCAWHLGELVWCTC, wherein the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a naturally occurring protein, and X is an amino acid residue described herein, e.g., one suitable for connection to another moiety (e.g., an amino acid residue containing -COOH, or a salt or activated form thereof, e.g., D, E, etc.). In some embodiments, the peptide unit is or comprises a sequence selected from CDCAWHLGELVWCTC, wherein the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a naturally occurring protein. In some embodiments, the peptide unit is or comprises CDCAWHLGELVWCTC, wherein the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a naturally occurring protein. In some embodiments, the peptide unit is or comprises a sequence selected from CDCAWDLGELVWCTC, wherein the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a naturally occurring protein. In some embodiments, the peptide unit is or comprises CDCAWDLGELVWCTC, wherein the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a naturally occurring protein. In some embodiments, the peptide unit is or comprises a sequence selected from Fc-III-4c. In some embodiments, the peptide unit is or comprises a sequence selected from FcRM. In some embodiments, the peptide unit is or comprises a cyclic peptide unit. In some embodiments, the cyclic peptide unit comprises an amide group formed by a side chain amino group and a C-terminal -COOH.Those skilled in the art will understand that in various embodiments, when a peptide unit is connected to another moiety, the amino acid residue of the peptide unit can be connected at various positions, e.g., via its backbone, its side chain, etc. In some embodiments, the amino acid residue is modified for connection. In some embodiments, the amino acid residue is replaced with another suitable residue for connection while maintaining one or more properties and / or activities of the peptide unit (e.g., binding to an antibody described herein). For example, in some embodiments, the amino acid residue is replaced with an amino acid residue having a side chain comprising -COOH, or a salt or activated form thereof (e.g., the side chain is -CH-COOH, or a salt or activated form thereof). As exemplified herein, in various sequences, H may be replaced with D (e.g., in various peptide units comprising WHL). In some embodiments, the peptide unit is connected to another moiety via -COOH, or a salt or activated form thereof, e.g., via the formation of -CON(R')-. In some embodiments, R' is -H. In some embodiments, -COOH is in the side chain of the amino acid residue. In some embodiments, in a sequence described herein (e.g., DCAWHLGELVWCT), 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally replaced with another amino acid residue, 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally deleted, and / or 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally inserted. In some embodiments, the peptide moiety is connected to the remainder of the molecule through its N-terminus. In some embodiments, it is connected to the remainder of the molecule through its C-terminus. In some embodiments, it is connected to the remainder of the molecule through the side chain of an amino acid residue (e.g., the various X residues described in this disclosure). In some embodiments, two cysteine ​​residues may independently and optionally form a disulfide bond. In some embodiments, the total number of substitutions, deletions, and insertions is 10 or less (e.g., 0, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or less).In some embodiments, the total number is 0. In some embodiments, the total number is 1 or less. In some embodiments, the total number is 2 or less. In some embodiments, the total number is 3 or less. In some embodiments, the total number is 4 or less. In some embodiments, the total number is 5 or less. In some embodiments, the total number is 6 or less. In some embodiments, the total number is 7 or less. In some embodiments, the total number is 8 or less. In some embodiments, the total number is 9 or less. In some embodiments, the total number is 10 or less. In some embodiments, there are no insertions. In some embodiments, there are no deletions.

[0054] In some embodiments, the antibody binding moiety comprises or has the structure DCAWHLGELVWCT, or a salt form thereof, where the two C residues are linked by -SS-. In some embodiments, the antibody binding moiety comprises or has the structure DCAWHLGELVWCT, or a salt form thereof, where the N-terminus is capped with RC(O)-. In some embodiments, R is methyl. In some embodiments, the antibody binding moiety is connected to the remainder of the molecule via its C-terminus.

[0055] In some embodiments, -(Xaa)z- is [X 1 ] p1 [X 2 ] p2 -X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 -[X 13 ] p13 -[X 14 ] p14 [X 15 ] p15 [X 16 ] p16 wherein X is or comprises 1 , X 2 , X 3 , X 4 , X 5 , X6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 Each of p1, p2, p13, p14, p15, and p16 is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 Each of X is independently an amino acid residue of an amino acid of formula AI. 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 Each of X is independently a naturally occurring amino acid residue. 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 One or more of are independently a non-natural amino acid residue as described in this disclosure.

[0056] In some embodiments, a peptide unit comprises a functional group on an amino acid residue that can react with a functional group on another amino acid residue. In some embodiments, a peptide unit comprises an amino acid residue having a side chain that comprises a functional group that can react with another functional group on the side chain of another amino acid residue to form a linkage (see, e.g., Table A-1, Table 1, etc.). In some embodiments, a functional group on one amino acid residue is connected to a functional group on another amino acid residue to form a linkage (or bridge). The linkage is attached to a backbone atom of the peptide unit, but does not include a backbone atom. In some embodiments, a peptide unit comprises a linkage formed by two side chains of non-adjacent amino acid residues. In some embodiments, the linkage is attached to two backbone atoms of two non-adjacent amino acid residues. In some embodiments, both backbone atoms attached to the linkage are carbon atoms. In some embodiments, the linkage is formed by a linkage formed by two side chains of non-adjacent amino acid residues. b It has the structure of L b is the L described in this disclosure a and L a is not a covalent bond. a In some embodiments, L a In some embodiments, -Cy- includes -Cy-, where -Cy- is an optionally substituted heteroaryl. [ka] is. In some embodiments, L a teeth, [ka] is. In some embodiments, such L a can be formed by the -N3 group of the side chain of one amino acid residue and the -≡- of the side chain of another amino acid residue. In some embodiments, the linkage is formed through the connection of two thiol groups (e.g., of two cysteine ​​residues). In some embodiments, L a In some embodiments, L ais -CH2-SS-CH2-. In some embodiments, the linkage is formed through the connection of an amino group (e.g., -NH2 of the side chain of a lysine residue) and a carboxylic acid group (e.g., -COOH of the side chain of an aspartic acid or glutamic acid residue). In some embodiments, L a In some embodiments, L a In some embodiments, L a is -CHCONH-(CH)-. In some embodiments, L a comprises -C(O)-N(R')-, where R' is R and, together with the R groups on the peptide backbone, forms a ring (e.g., A-34). a is —(CH)—N(R′)—CO—(CH). In some embodiments, —Cy- is optionally substituted phenylene. In some embodiments, —Cy- is optionally substituted 1,2-phenylene. In some embodiments, L a teeth, [ka] is. In some embodiments, L a teeth, [ka] is. In some embodiments, L a is an optionally substituted divalent C 20 In some embodiments, L a is optionally substituted -(CH2)9-CH=CH-(CH2)9-. In some embodiments, L a is -(CH2)3-CH=CH-(CH2)3-.

[0057] In some embodiments, the two amino acid residues joined at the linkage are separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more than 15 amino acid residues between them (excluding the two amino acid residues joined at the linkage). In some embodiments, the number is 1. In some embodiments, the number is 2. In some embodiments, the number is 3. In some embodiments, the number is 4. In some embodiments, the number is 5. In some embodiments, the number is 6. In some embodiments, the number is 7. In some embodiments, the number is 8. In some embodiments, the number is 9. In some embodiments, the number is 10. In some embodiments, the number is 11. In some embodiments, the number is 12. In some embodiments, the number is 13. In some embodiments, the number is 14. In some embodiments, the number is 15.

[0058] In some embodiments, each of p1, p2, p13, p14, p15, and p16 is 0. In some embodiments, -(Xaa)z- is -X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; X 6 is Xaa A or Xaa P and X 9 is Xaa N and X 12 is Xaa Aor Xaa P is.

[0059] In some embodiments, X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 Each of X is independently an amino acid residue of an amino acid of formula AI described in the present disclosure. 5 is Xaa A or Xaa P In some embodiments, X 5 is Xaa A In some embodiments, X 5 is Xaa P In some embodiments, X 5 is an amino acid residue whose side chain comprises an optionally substituted saturated, partially saturated, or aromatic ring. 5 teeth, [ka] is. In some embodiments, X 5 teeth, [ka] is. In some embodiments, X 6 is Xaa A In some embodiments, X 6 is Xaa P In some embodiments, X 6 is His. 12 is Xaa A In some embodiments, X 12 is Xaa P In some embodiments, X 9 is Asp. 9is Glu. 12 teeth, [ka] is. In some embodiments, X 12 teeth, [ka] is. In some embodiments, X 7 , X 10 , and X 11 each independently being an amino acid residue having a hydrophobic side chain ("hydrophobic amino acid residue", Xaa H In some embodiments, X 7 is Xaa H In some embodiments, X 7 teeth, [ka] is. In some embodiments, X 7 In some embodiments, X is Val. 10 is Xaa H In some embodiments, X 10 is Met. 10 teeth, [ka] is. In some embodiments, X 11 is Xaa H In some embodiments, X 11 teeth, [ka] is. In some embodiments, X 8 is Gly. 4 is Pro. In some embodiments, X 3 is Lys.12 -COOH of Lys(X 3 ) and forms an amide bond with the amino group in the side chain of Lys(X 3 The other amino group of ) is connected to a linker moiety and then to an antibody binding moiety.

[0060] In some embodiments, -(Xaa)z- is -X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; At least two amino acid residues are linked by one or more L b Connected via L b is C1~C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is bound to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 6 is Xaa A or Xaa P and X 9 is Xaa N and X 12 is Xaa A or Xaa P is.

[0061] In some embodiments, X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, X 5 and X 10 L b In some embodiments, one link L b In some embodiments, X 6 is Xaa A In some embodiments, X 6 is Xaa P In some embodiments, X 6 is His. 9 is Asp. 9 is Glu. 12 is Xaa A In some embodiments, X 12 teeth, [ka] is. In some embodiments, X 12 teeth, [ka] is. In some embodiments, X 12 teeth, [ka] is. In some embodiments, X 4 , X 7 , and X 11 Each of Xaa H In some embodiments, X 4 is Xaa H In some embodiments, X 4 is Ala. 7 is Xaa H In some embodiments, X 7 teeth, [ka] is. In some embodiments, X 11 is Xaa H In some embodiments, X 11 teeth, [ka] is. In some embodiments, X 8 is Gly. 3 is Lys. 12 -COOH of Lys(X 3 ) and forms an amide bond with the amino group in the side chain of Lys(X 3 The other amino group of L is connected to a linker moiety and then to an antibody binding moiety. b teeth, [ka] is. In some embodiments, L b teeth, [ka] is. In some embodiments, L bconnects two alpha carbon atoms of two different amino acid residues. 5 and X 10 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH2-SS-CH2-).

[0062] In some embodiments, -(Xaa)z- is -X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; At least two amino acid residues are linked by one or more L b are connected via L b is C1~C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is bound to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 4 is Xaa A and X 5 is Xaa A or Xaa P and X 8 is Xaa N and X 11 is Xaa A is.

[0063] In some embodiments, X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, one link L b In some embodiments, X 2 and X 12 L b In some embodiments, L b is -CH-SS-CH-. In some embodiments, L b is -CH-CH-S-CH-. In some embodiments, L b teeth, [ka] is. In some embodiments, L b teeth, [ka] is. In some embodiments, L bis -CH2CH2CO-N(R')-CH2CH2-. In some embodiments, R', together with the R group on the backbone atom to which -N(R')-CH2CH2- is attached, forms a ring, e.g., A-34. In some embodiments, the ring formed is 3, 4, 5, 6, 7, or 8-membered. In some embodiments, the ring formed is monocyclic. In some embodiments, the ring formed is saturated. In some embodiments, L b teeth, [ka] is. In some embodiments, L b connects two alpha carbon atoms of two different amino acid residues. 4 is Xaa A In some embodiments, X 4 is Tyr. 5 is Xaa A In some embodiments, X 5 is Xaa P In some embodiments, X 5 is His. 8 is Asp. 8 is Glu. X 11 is Tyr. 2 and X 12 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 3 , X 6 , X 9 , and X 10 Each of Xaa H In some embodiments, X 3 is Xaa H In some embodiments, X 3 is Ala. 6 is Xaa H In some embodiments, X6 is Leu. 9 is Xaa H In some embodiments, X 9 is Leu. 9 teeth, [ka] is. In some embodiments, X 10 is Xaa H In some embodiments, X 10 In some embodiments, X is Val. 10 teeth, [ka] is. In some embodiments, X 7 In some embodiments, p1 is 1. In some embodiments, X 1 is Asp. In some embodiments, p13 is 1. In some embodiments, p14, p15, and p16 are 0. In some embodiments, X 13 is a polar uncharged side chain (e.g., a "polar uncharged amino acid residue" at physiological pH, Xaa L In some embodiments, X is an amino acid residue comprising 13 is Thr. In some embodiments, X 13 In some embodiments, p13 is 0. In some embodiments, R c is —NHCHCH(OH)CH. In some embodiments, R c is (R)-NHCHCH(OH)CH. In some embodiments, R c is (S)-NHCH2CH(OH)CH3.

[0064] In some embodiments, -(Xaa)z- is -X 2 X 3 X 4 X 5 X 6 X 7 X8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; At least two amino acid residues are linked by one or more L b are connected via L b is C1~C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is bound to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 5 is Xaa A or Xaa P and X 8 is Xaa N and X 11 is Xaa A is.

[0065] In some embodiments, X 2 , X 3 , X 4 , X 5 , X 6 , X7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, one link L b In some embodiments, there are two or more linked L b In some embodiments, there are two linked L b In some embodiments, X 2 and X 12 L b In some embodiments, X 4 and X 9 L b In some embodiments, X 4 and X 10 L b In some embodiments, L b is -CH-SS-CH-. In some embodiments, L b teeth, [ka] is. In some embodiments, L b teeth, [ka] is. In some embodiments, X 2 and X 12 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 4 and X 10 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 4and X 9 L b Connected by L b teeth, [ka] is. In some embodiments, X 4 and X 9 L b Connected by L b teeth, [ka] is. In some embodiments, X 5 is Xaa A In some embodiments, X 5 is Xaa P In some embodiments, X 5 is His. 8 is Asp. 8 is Glu. 11 is Tyr. 11 teeth, [ka] is. In some embodiments, X 2 and X 12 L b Connected by L b is -CH-S-CHCH-. In some embodiments, L b connects two alpha carbon atoms of two different amino acid residues. 3 , X 6 , and X 9 Each of Xaa H In some embodiments, X 3 is Xaa H In some embodiments, X 3 is Ala. 6 is XaaH In some embodiments, X 6 is Leu. 6 teeth, [ka] is. In some embodiments, X 9 is Xaa H In some embodiments, X 9 is Leu. 9 teeth, [ka] is. In some embodiments, X 10 is Xaa H In some embodiments, X 10 In some embodiments, X is Val. 7 In some embodiments, p1 is 1. In some embodiments, X 1 is Xaa N In some embodiments, X 1 is Asp. 1 In some embodiments, p13 is 1. In some embodiments, p14, p15, and p16 are 0. In some embodiments, X 13 is Xaa L In some embodiments, X 13 is Thr. In some embodiments, X 13 is Val.

[0066] In some embodiments, -(Xaa)z- is -X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 X 13 X 14 X15 X 16 - is or comprises -, wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , and X 16 are independently an amino acid residue; At least two amino acid residues are linked together by the L b Connected via L b is C1~C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is bound to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 3 is Xaa N and X 6 is Xaa A and X 7 is Xaa A or Xaa P and X 9 is Xaa N and X 13 is Xaa A is.

[0067] In some embodiments, X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, one link L b In some embodiments, there are two or more linked L b In some embodiments, there are two linked L b In some embodiments, X 2 L b By X 16 In some embodiments, X 4 L b By X 14 In some embodiments, X 2 and X 16 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 4 and X 14 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, L b connects two alpha carbon atoms of two different amino acid residues. 3 is Asp. 3 is Glu. 5 is Xaa H In some embodiments, X 5 is Ala. 6 is Xaa AIn some embodiments, X 6 is Tyr. 7 is Xaa A In some embodiments, X 7 is Xaa P In some embodiments, X 7 is His. 8 is Xaa H In some embodiments, X 8 is Ala. 9 is Gly. 10 is Asp. 10 is Glu. 11 is Xaa H In some embodiments, X 11 is Leu. 12 is Xaa H In some embodiments, X 12 In some embodiments, X is Val. 13 is Xaa A In some embodiments, X 13 is Tyr. 15 is Xaa L In some embodiments, X 15 is Thr. In some embodiments, X 15 In some embodiments, p1 is 1. In some embodiments, X 1 is Xaa N In some embodiments, X 1 is Asp. 1 is Glu.

[0068] As will be appreciated by those skilled in the art, an amino acid residue may be replaced by another amino acid residue having similar properties, e.g., a Xaa H (e.g., Val, Leu, etc.) can be replaced by another Xaa H(e.g., Leu, Ile, Ala, etc.), and certain Xaa A is another Xaa A Xaa may be replaced by P is another Xaa P Xaa may be replaced by N is another Xaa N Xaa may be replaced by L is another Xaa L may be substituted with, etc.

[0069] In some embodiments, the antibody binding moiety is or comprises an optionally substituted moiety of Table A-1. In some embodiments, the protein binding moiety is or comprises an optionally substituted moiety of Table A-1. In some embodiments, the antibody binding moiety, e.g., a universal antibody binding moiety, is or comprises an optionally substituted moiety of Table A-1. In some embodiments, the antibody binding moiety is selected from Table A-1. In some embodiments, the protein binding moiety is selected from Table A-1. In some embodiments, the antibody binding moiety, e.g., a universal antibody binding moiety, is selected from Table A-1. In some embodiments, the C-terminus and / or N-terminus are optionally capped (e.g., for the C-terminus, by changing -COOH to -C(O)N(R') such as -C(O)NH; for the N-terminus, by adding R'C(O)- such as CHC(O)- to the amino group).

[0070] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8]

[0071] In some embodiments, the antibody-binding moiety is an antibody-binding moiety described herein. In some embodiments, the protein-binding moiety is an antibody-binding moiety described herein. In some embodiments, the —COOH and / or amino group of an amino acid residue, e.g., a C-terminal or N-terminal amino acid residue, is optionally capped. For example, in some embodiments, a —COOH group (e.g., a C-terminal —COOH) is amidated (e.g., converted to —CON(R′)2, e.g., —C(O)NHR (e.g., —C(O)NH2)), and in some embodiments, an amino group, e.g., —NH2 (e.g., an N-terminal —NH2) is capped with R′— or R′C(O)— (e.g., in some embodiments, by converting —NH2 to —NHR′ (e.g., —NHC(O)R, (e.g., —NHC(O)CH3))).

[0072] In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-1. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-2. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-3. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-4. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-5. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-6. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-7. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-8. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-9. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-10. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-11. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-12. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-13. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-14. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-15. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-16. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-17. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-18. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-19. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-20. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-21.In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-22. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-23. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-24. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-25. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-26. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-27. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-28. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-29. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-30. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-31. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-32. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-33. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-34. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-35. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-36. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-37. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-38. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-39. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-40. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-41. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-42.In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-43. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-44. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-45. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-46. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-47. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-48. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-49. In some embodiments, the antibody binding moiety is or comprises an optionally substituted A-50. In some embodiments, such an antibody binding moiety is an antibody binding moiety. In some embodiments, such an antibody binding moiety is a universal antibody binding moiety.

[0073] In some embodiments, the antibody binding moiety is A-1. In some embodiments, the antibody binding moiety is A-2. In some embodiments, the antibody binding moiety is A-3. In some embodiments, the antibody binding moiety is A-4. In some embodiments, the antibody binding moiety is A-5. In some embodiments, the antibody binding moiety is A-6. In some embodiments, the antibody binding moiety is A-7. In some embodiments, the antibody binding moiety is A-8. In some embodiments, the antibody binding moiety is A-9. In some embodiments, the antibody binding moiety is A-10. In some embodiments, the antibody binding moiety is A-11. In some embodiments, the antibody binding moiety is A-12. In some embodiments, the antibody binding moiety is A-13. In some embodiments, the antibody binding moiety is A-14. In some embodiments, the antibody binding moiety is A-15. In some embodiments, the antibody binding moiety is A-16. In some embodiments, the antibody binding moiety is A-17. In some embodiments, the antibody binding moiety is A-18. In some embodiments, the antibody binding moiety is A-19. In some embodiments, the antibody binding moiety is A-20. In some embodiments, the antibody binding moiety is A-21. In some embodiments, the antibody binding moiety is A-22. In some embodiments, the antibody binding moiety is A-23. In some embodiments, the antibody binding moiety is A-24. In some embodiments, the antibody binding moiety is A-25. In some embodiments, the antibody binding moiety is A-26. In some embodiments, the antibody binding moiety is A-27. In some embodiments, the antibody binding moiety is A-28. In some embodiments, the antibody binding moiety is A-29. In some embodiments, the antibody binding moiety is A-30. In some embodiments, the antibody binding moiety is A-31. In some embodiments, the antibody binding moiety is A-32. In some embodiments, the antibody binding moiety is A-33. In some embodiments, the antibody binding moiety is A-34. In some embodiments, the antibody binding moiety is A-35. In some embodiments, the antibody binding moiety is A-36. In some embodiments, the antibody binding moiety is A-37. In some embodiments, the antibody binding moiety is A-38.In some embodiments, the antibody binding moiety is A-39. In some embodiments, the antibody binding moiety is A-40. In some embodiments, the antibody binding moiety is A-41. In some embodiments, the antibody binding moiety is A-42. In some embodiments, the antibody binding moiety is A-43. In some embodiments, the antibody binding moiety is A-44. In some embodiments, the antibody binding moiety is A-45. In some embodiments, the antibody binding moiety is A-46. In some embodiments, the antibody binding moiety is A-47. In some embodiments, the antibody binding moiety is A-48. In some embodiments, the antibody binding moiety is A-49. In some embodiments, such an antibody binding moiety is an antibody binding moiety. In some embodiments, such an antibody binding moiety is a universal antibody binding moiety.

[0074] In some embodiments, the antibody binding moiety, e.g., a protein binding moiety (e.g., an antibody binding moiety (e.g., a universal antibody binding moiety)), comprises a peptide unit and is connected to a linker moiety through the C-terminus of the peptide unit. In some embodiments, it is connected to a linker moiety through the N-terminus of the peptide unit. In some embodiments, it is connected to a linker through a side chain group of the peptide unit. In some embodiments, the antibody binding moiety, e.g., a universal antibody binding moiety, comprises a peptide unit and is connected to the antibody binding moiety through the C-terminus of the peptide unit, optionally through a linker moiety. In some embodiments, the antibody binding moiety, e.g., a protein binding moiety (e.g., an antibody binding moiety (e.g., a universal antibody binding moiety)), comprises a peptide unit and is connected to the antibody binding moiety through the N-terminus of the peptide unit, optionally through a linker moiety. In some embodiments, the antibody binding moiety, e.g., a protein binding moiety (e.g., an antibody binding moiety (e.g., a universal antibody binding moiety)), comprises a peptide unit and is connected to the antibody binding moiety through a side chain of the peptide unit, optionally through a linker moiety.

[0075] In some embodiments, the antibody binding moiety is or comprises (DCAWHLGELVWCT)-, in which 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally replaced with another amino acid residue, 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally deleted, and / or 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally inserted. In some embodiments, it is connected to the rest of the molecule through its N-terminus. In some embodiments, it is connected to the rest of the molecule through its C-terminus. In some embodiments, it is connected to the rest of the molecule through the side chain of an amino acid residue (e.g., the various X residues described in this disclosure). In some embodiments, the two cysteine ​​residues form a disulfide bond. In some embodiments, the antibody binding moiety is [ka] , [ka] , [ka] , or [ka] wherein X is or comprises an amino acid residue attached to the remainder of the compound or agent, wherein 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally replaced with another amino acid residue, 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally deleted, and / or 1 to 5 (e.g., 1, 2, 3, 4, or 5) amino acid residues may be independently and optionally inserted. In some embodiments, the total number of substitutions, deletions, and insertions is 10 or less (e.g., 0, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or less). In some embodiments, the total number is 0. In some embodiments, the total number is 1 or less. In some embodiments, the total number is 2 or less. In some embodiments, the total number is 3 or less. In some embodiments, the total number is 4 or less. In some embodiments, the total number is 5 or less. In some embodiments, the total number is 6 or less. In some embodiments, the total number is 7 or less. In some embodiments, the total number is 8 or less. In some embodiments, the total number is 9 or less. In some embodiments, the total number is 10 or less. In some embodiments, there are no insertions. In some embodiments, there are no deletions. In some embodiments, there are no replacements. In some embodiments, the antibody binding moiety is [ka] , [ka] , [ka] , or [ka] wherein X is or comprises an amino acid residue attached to the remainder of the compound or agent. In some embodiments, X is -N(R')-CH(-)-C(O)-. In some embodiments, X is -N(R')-CH(-L LG1In some embodiments, X is —N(R′)—CH(-L LG1 -L LG2 In some embodiments, X is —N(R′)—CH(-L LG1 -L LG2 -L LG3 In some embodiments, X is —N(R′)—CH(-L LG1 -L LG2 -L LG3 -L LG4 In some embodiments, the antibody binding moiety is: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, X is or comprises: [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of [ka] In some embodiments, X is a residue of. In some embodiments, X is K. In some embodiments, X is D. In some embodiments, X is a residue of Dab. In some embodiments, X is E. In some embodiments, X is [ka] In some embodiments, the present disclosure provides a residue of [ka] , [ka] , [ka] , [ka] , [ka] , [ka] , [ka] , [ka] , or [ka] or a salt thereof, or an ester thereof, or an activated ester thereof, or a stereoisomer thereof, or an ester or activated ester of a stereoisomer thereof. In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0076] In some embodiments, the antibody binding moiety, e.g., universal antibody binding moiety, is or comprises a small molecular entity, e.g., having a molecular weight of less than 10,000, 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, 2,000, 1,500, 1,000, etc. Suitable such antibody binding moieties include, for example, small molecule Fc binder moieties such as those described in US 9,745,339, US 201 / 30131321. In some embodiments, the antibody binding moiety is of a structure such that the corresponding compound is a compound described in US 9,745,339 or US 2013 / 0131321 (each of which compounds is independently incorporated herein by reference). In some embodiments, the antibody binding moiety ABT is structured such that H-ABT is a compound described in US9,745,339 or US2013 / 0131321 (each of which compounds is independently incorporated herein by reference). In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0077] In some embodiments, the antibody binding moiety is optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises optionally substituted [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0078] In some embodiments, the antibody binding moiety is [ka] wherein each variable is independently as described herein. In some embodiments, m is 4 to 13. In some embodiments, the antibody binding moiety is [ka] wherein b is 1 to 20, and each other variable is independently as described herein. In some embodiments, b is 4 to 13. In some embodiments, the antibody binding moiety, e.g., R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, R c -(Xaa)z- is [ka] In some embodiments, -NH- is or comprises R c In some embodiments, R c is RC(O)—. In some embodiments, Rc is CH3C(O)-. In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0079] In some embodiments, the antibody binding moiety, e.g., [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, the antibody binding moiety is or comprises, for example, [ka] , or R c -(Xaa)z- is [ka] In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0080] In some embodiments, the antibody binding moiety, e.g., R c-(Xaa)z- is or includes a Z33 peptide moiety. In some embodiments, an antibody binding moiety, e.g., R c -(Xaa)z- is or comprises -FNMQQQRRFYEALHDPNLNEEQRNAKIKSIRDD-NH2 or a fragment thereof. In some embodiments, the antibody binding moiety, e.g., R c -(Xaa)z- is or comprises FNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC or a fragment thereof. In some embodiments, the antibody binding moiety, e.g., [ka] , or R c-(Xaa)z- is FNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC, RGNCAYHRGQLVWCTYH, RGNCAYHKGQLVWCTYH, RGNCKYHRGQLVWCTYH, RGNCAWHRGKLVWCTYH, RGNCKWHRGELVWCTYH, RGNCKWHRGQLVWCTYH, RGNCKYHLGELVWCTYH, RGNCKYHLGQLVWCTYH, DCKWHLGELVWCT, DCKYHLGELVWCT, DCKWHRGELVWCT, DCKWHLGQLVWCT, DCKYHRGELVWCT, DCKYHLGQLVWCT, DCKWHRGQLVWCT, DCKYHRGQLVWCT, FNKQCQRRFYEALHDPNLNEEQRNARIRSIRDDC, FNMQCQRRFYEALHDPNLNEEQRNARIRSIKDDC, FNMQCQRRFYEALHDPNLNKEQRNARIRSIRDDC, FNMQCQRRFYEALHDPNLNEEQRNARIRSIRDDC, RGNCAWHLGQLVWCKYH, RGNCAWHLGELVWCKYH, RGNCAYHLGQLVWCTKH, RGNCAYHLGQLVWCTYK, RGNCAYHRGQLVWCTKH, KNMQCQRRFYEALHDPNLNEEQRNARIRSIRDDC, FNMQCQKRFYEALHDPNLNEEQRNARIRSIRDDC, FNMQCQRRFYEAKHDPNLNEEQRNARIRSIRDDC, FNMQCQRRFYEALHDPNLNEEQRKARIRSIRDDC, FNMQCQRRFYEALHDPNLNKEQRNARIRSIRDDC, FNMQCQRRFYEALHDPNLNEEQRNARIRSIKDDC, FNKQCQRRFYEALHDPNLNEEQRNARIRSIRDDC, FNMQCQKRRFYEALHDPNLNEEQRNARIRSIRDDC, FNMQCQRRFYEALHDPNLNEEQRNARIRSIRKDC, Fc-III, FcBP-2, Fc-III-4C,

Chem.

[0081] In some embodiments, the antibody binding moiety, e.g., [ka] , or R c -(Xaa)z- is (X 1~3 )-C-(X2)-H-(Xaa1)-G-(Xaa2)-LVWC-(X 1~3), wherein each of X and Xaa is independently an amino acid residue, optionally not a cysteine ​​residue. In some embodiments, Xaa1 is R, L, L, D, E, a 2-aminosuberic acid residue, or a diaminopropionic acid residue. In some embodiments, Xaa2 is L, D, E, N, or Q. In some embodiments, Xaa1 is a lysine residue, a cysteine ​​residue, an aspartic acid residue, a glutamic acid residue, a 2-aminosuberic acid residue, or a diaminopropionic acid residue. In some embodiments, Xaa2 is a glutamic acid residue or an aspartic acid residue. In some embodiments, Xaa1 is an arginine residue or a leucine residue. In some embodiments, Xaa2 is a lysine residue, a glutamine residue, or an aspartic acid residue. In some embodiments, such antibody binding moieties are antibody binding moieties.

[0082] In some embodiments, the antibody binding moiety, e.g., [ka] , or R c-(Xaa)z- is or includes (X1-3)-C-(Xaa3)-(xaa4)-H-(Xaa1)-G-(Xaa2)-LVWC-(Xaa5)-(Xaa6)-(Xaa7), where each of X and Xaa is independently an amino acid residue, optionally not a cysteine ​​residue. In some embodiments, Xaa3 is an alanine residue or a lysine residue. In some embodiments, Xaa4 is a tryptophan residue or a tyrosine residue. In some embodiments, Xaa1 is an arginine residue, leucine residue, lysine residue, aspartic acid residue, glutamic acid residue, 2-aminosuberic acid residue, or diaminopropionic acid residue. In some embodiments, Xaa2 is a lysine residue, glutamine residue, glutamic acid residue, asparagine residue, or aspartic acid residue. In some embodiments, Xaa5 is a threonine residue or a lysine residue. In some embodiments, Xaa6 is a tyrosine residue, a lysine residue, or is absent. In some embodiments, Xaa7 is a histidine residue, a lysine residue, or is absent. In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0083] In some embodiments, the antibody binding moiety, e.g., [ka] , or R c-(Xaa)z- is or includes DC-(Xaa3)-(Xaa4)-H-(Xaa1)-G-(Xaa2)-LVWC-(Xaa5)-(Xaa6)-(Xaa7), where each of X and Xaa is independently an amino acid residue, optionally not a cysteine ​​residue. In some embodiments, Xaa3 is an alanine residue or a lysine residue. In some embodiments, Xaa4 is a tryptophan residue or a tyrosine residue. In some embodiments, Xaa1 is an arginine residue, leucine residue, lysine residue, aspartic acid residue, glutamic acid residue, 2-aminosuberic acid residue, or diaminopropionic acid residue. In some embodiments, Xaa2 is a lysine residue, glutamine residue, glutamic acid residue, asparagine residue, or aspartic acid residue. In some embodiments, Xaa5 is a threonine residue or a lysine residue. In some embodiments, Xaa6 is a tyrosine residue, a lysine residue, or is absent. In some embodiments, Xaa7 is a histidine residue, a lysine residue, or is absent. In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0084] In some embodiments, the antibody binding moiety, e.g., [ka] , or R c-(Xaa)z- is or comprises DC-(Xaa3)-(Xaa4)-H-(Xaa1)-G-(Xaa2)-LVWCT, where each of X and Xaa is independently an amino acid residue, optionally not a cysteine ​​residue. In some embodiments, Xaa3 is an alanine residue or a lysine residue. In some embodiments, Xaa4 is a tryptophan residue or a tyrosine residue. In some embodiments, Xaa1 is an arginine residue, leucine residue, lysine residue, aspartic acid residue, glutamic acid residue, 2-aminosuberic acid residue, or diaminopropionic acid residue. In some embodiments, Xaa2 is a lysine residue, glutamine residue, glutamic acid residue, asparagine residue, or aspartic acid residue. In some embodiments, such antibody binding moieties are antibody binding moieties.

[0085] In some embodiments, the antibody binding moiety, e.g., [ka] , or R c-(Xaa)z- is or includes RGNC-(Xaa3)-(Xaa4)-H-(Xaa1)-G-(Xaa2)-LVWC-(Xaa5)-(Xaa6)-(Xaa7), where each of X and Xaa is independently an amino acid residue, optionally not a cysteine ​​residue. In some embodiments, Xaa3 is an alanine residue or a lysine residue. In some embodiments, Xaa4 is a tryptophan residue or a tyrosine residue. In some embodiments, Xaa1 is an arginine residue, leucine residue, lysine residue, aspartic acid residue, glutamic acid residue, 2-aminosuberic acid residue, or diaminopropionic acid residue. In some embodiments, Xaa2 is a lysine residue, glutamine residue, glutamic acid residue, asparagine residue, or aspartic acid residue. In some embodiments, Xaa5 is a threonine residue or a lysine residue. In some embodiments, Xaa6 is a tyrosine residue, a lysine residue, or is absent. In some embodiments, Xaa7 is a histidine residue, a lysine residue, or is absent. In some embodiments, such an antibody binding moiety is an antibody binding moiety.

[0086] In some embodiments, the antibody binding moiety, e.g., the various antibody binding moieties described above, is a protein binding moiety. In some embodiments, the antibody binding moiety is an antibody binding moiety. In some embodiments, the LG is or comprises such an antibody binding moiety. In some embodiments, the LG is or comprises a protein binding moiety. In some embodiments, the LG is or comprises an antibody binding moiety.

[0087] In some embodiments, antibody binding moieties, e.g., antibody binding moieties, and techniques useful for developing and / or evaluating such moieties, are described in, e.g., Alves, Langmuir 2012, 28, 9640-9648; Choe et al., Materials 2016, 9, 994, doi:10.3390 / ma9120994; Gupta et al., Nature Biomedical Engineering, vol. 3, 2019, 917-929; Muguruma, et al., ACS Omega 2019, 4, 14390-14397, doi:10.1021 / acsomega.9b01104; Yamada, et al., Angew Chem Int Ed Engl. 2019 Apr 16;58(17):5592-5597, doi:10.1002 / anie.201814215, Kruljec, et al., Bioconjug Chem. 2017, 28(8):2009-2030, doi:10.1021 / acs.bioconjchem.7b00335 (e.g., Fabsorbents, triazines, etc.), Kruljec, et al., Bioconjugate Chem. 2018, 29, 8, 2763-2775, doi:10.1021 / acs.bioconjchem.8b00395, WO2012017021A2, etc., each of which binding moieties (e.g., antibody-binding moieties) are incorporated herein by reference in their entirety.

[0088] In some embodiments, the antibody binding moiety, e.g., the protein binding moiety (e.g., antibody binding moiety), is an affinity substance described in AU2018259856 or WO2018199337, each of which affinity substances is incorporated herein by reference.

[0089] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is or includes an adaptor protein agent, e.g., as described in Hui, et al., Bioconjugate Chem. 2015, 26, 1456-1460, doi:10.1021 / acs.bioconjchem.5b00275. In some embodiments, when utilized in accordance with the present disclosure, the adaptor protein does not require a reactive residue (e.g., BPA) to achieve one or more or all of the benefits.

[0090] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is or includes a triazine moiety, e.g., one described in US2009 / 0286693. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is an antibody binding moiety of a compound whose corresponding compound is a compound described in US2009 / 0286693, which compounds are independently incorporated by reference herein. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is ABT. In some embodiments, ABT is of a structure such that H-ABT is a compound described in US2009 / 0286693, which compounds are independently incorporated by reference herein. In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0091] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is or includes a triazine moiety, such as those described in Teng, et al., A strategy for the generation of biomimetic ligands for affinity chromatography. Combinatorial synthesis and biological evaluation of an IgG binding ligand, J. Mol. Recognit. 1999;12:67-75 ("Teng"). In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is structured such that its corresponding compound is a compound described in Teng, which compounds are independently incorporated by reference herein. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, ABT, is structured such that H-ABT is a compound described in Teng, which compounds are independently incorporated by reference herein. In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0092] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is a triazine moiety, e.g., those described in Uttamchandani, et al., Microarrays of Tagged Combinatorial Triazine Libraries in the Discovery of Small-Molecule Ligands of Human IgG, J Comb Chem. 2004 Nov-Dec;6(6):862-8 ("Uttamchandani"). In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is of a structure such that its corresponding compound is a compound described in Uttamchandani, which compounds are independently incorporated by reference herein. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, ABT, is of a structure such that H-ABT is a compound described in Uttamchandani, which compounds are independently incorporated by reference herein. In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0093] In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein A. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein G. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein L. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein Z. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein LG. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein LA. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein AG. In some embodiments, the antibody binding moiety is described in Choe, W., Durgannavar, TA, & Chung, SJ (2016). Fc-binding ligands of immunoglobulin G: An overview of high affinity proteins and peptides. Materials, 9(12). https: / / doi.org / 10.3390 / ma9120994.

[0094] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is capable of binding to a nucleotide binding site. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is a small molecule moiety capable of binding to a nucleotide binding site. In some embodiments, the small molecule is tryptamine. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, ABT, is structured such that H-ABT is tryptamine. A particularly useful technique was described in Mustafaoglu, et al., Antibody Purification via Affinity Membrane Chromatography Method Utilizing Nucleotide Binding Site Targeting With A Small Molecule, Analyst. 2016 November 28;141(24):6571-6582.

[0095] Numerous techniques are available for identifying and / or evaluating and / or characterizing antibody binding moieties, including protein binding moieties (e.g., antibody binding moieties such as universal antibody binding moieties), and / or their use in the provided technologies, such as those described in WO / 2019 / 023501, which is incorporated herein by reference. In some embodiments, the antibody binding moiety is a moiety (e.g., a small molecule moiety, a peptide moiety, a nucleic acid moiety, etc.) that can selectively bind to IgG and, when used in the provided technologies, can provide and / or stimulate ADCC and / or ADCP. In some embodiments, peptide display techniques (e.g., phase display, acellular display, etc.) can be used to identify the antibody binding moiety. In some embodiments, the antibody binding moiety is a moiety (e.g., a small molecule moiety, a peptide moiety, a nucleic acid moiety, etc.) that can bind to IgG and, optionally, compete with known antibody binders (e.g., Protein A, Protein G, Protein L, etc.).

[0096] As will be appreciated by those skilled in the art, antibodies of various properties and activities (e.g., antibodies recognizing different antigens, with optional modifications, etc.) can be targeted by the antibody binding moieties described in this disclosure. In some embodiments, such antibodies include, for example, antibodies administered to a subject for therapeutic purposes. In some embodiments, the antibody binding moieties described herein may bind to antibodies against different antigens, making them useful for conjugating moieties of interest to a variety of antibodies.

[0097] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is or comprises a meditope drug moiety. In some embodiments, meditope drugs are described, e.g., in US2019 / 0111149.

[0098] In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is capable of binding to human IgG. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, is capable of binding to rabbit IgG. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, binds to IgG1. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, binds to IgG2. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, binds to IgG3. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, binds to IgG4. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, binds to IgG1, IgG2 and / or IgG4. In some embodiments, the antibody binding moiety, e.g., the antibody binding moiety, binds to IgG1, IgG2 and IgG4.

[0099] In some embodiments, [ka] is utilized in the referenced art as a non-antibody binding moiety. In some embodiments, CH3- is utilized in the referenced art non-antibody binding moiety. In some embodiments, CH3C(O)- is utilized in the referenced art non-antibody binding moiety. In some embodiments, CH3C(O)NH- is utilized in the referenced art non-antibody binding moiety. In some embodiments, CH3C(O)NHCH2- is utilized in the referenced art non-antibody binding moiety. In some embodiments, CH3CH2- is utilized in the referenced art non-antibody binding moiety. In some embodiments, CH3CH2NH- is utilized in the referenced art non-antibody binding moiety. In some embodiments, CH3CH2NHC(O)- is utilized in the referenced art non-antibody binding moiety.

[0100] In some embodiments, the antibody binding moiety (e.g., antibody binding moiety) binds to a target (e.g., an antibody drug for the antibody binding moiety) with a Kd that is about 1 mM to 1 pM or less. In some embodiments, the Kd is about 1 mM, 0.5 mM, 0.2 mM, 0.1 mM, 0.05 mM, 0.02 mM, 0.01 mM, 0.005 mM, 0.002 mM, 0.001 mM, 500 nM, 200 nM, 100 nM, 50 nM, 20 nM, 10 nM, 5 nM, 2 nM, 1 nM, 0.5 nM, 0.2 nM, 0.1 nM, or less. In some embodiments, the Kd is about 1 mM or less. In some embodiments, the Kd is about 0.5 mM or less. In some embodiments, the Kd is about 0.1 mM or less. In some embodiments, the Kd is about 0.05 mM or less. In some embodiments, the Kd is about 0.01 mM or less. In some embodiments, the Kd is about 0.005 mM or less. In some embodiments, the Kd is about 0.001 mM or less. In some embodiments, the Kd is about 500 nM or less. In some embodiments, the Kd is about 200 nM or less. In some embodiments, the Kd is about 100 nM or less. In some embodiments, the Kd is about 50 nM or less. In some embodiments, the Kd is about 20 nM or less. In some embodiments, the Kd is about 10 nM or less. In some embodiments, the Kd is about 5 nM or less. In some embodiments, the Kd is about 2 nM or less. In some embodiments, the Kd is about 1 nM or less. For example, in some embodiments, the antibody binding moiety binds to an IgG antibody drug with a Kd described herein.

[0101] As will be appreciated by those skilled in the art, antibodies of various properties and activities (e.g., antibodies recognizing different antigens, with optional modifications, etc.) can be recruited by the antibody binding moieties described herein. In some embodiments, such antibodies include antibodies administered to a subject, for example, for therapeutic purposes. In some embodiments, antibodies recruited by antibody binding moieties include antibodies against different antigens. In some embodiments, antibodies recruited by antibody binding moieties include antibodies whose antigen is not present on the surface or cell membrane of a target cell. In some embodiments, antibodies recruited by antibody binding moieties include antibodies whose antigen is not present on the surface or cell membrane of a target cell. In some embodiments, an antigen on the surface of a target cell may interfere with the structure, conformation, and / or one or more properties and / or activities of a recruited antibody that binds to such antigen. In some embodiments, as will be appreciated by those skilled in the art, the provided technology comprises universal antibody binding moieties that recruit antibodies with diverse specificities, and wherein no more than 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% percent of the recruited antibodies are directed against the same antigen, protein, lipid, carbohydrate, etc. Among other advantages, one advantage of the present disclosure is that the provided technology comprises universal antibody binding moieties and can utilize a diverse pool of antibodies, such as those present in serum. In some embodiments, a universal antibody binding moiety of the present disclosure (e.g., in an ARM) contacts multiple antibodies, and no more than 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of the multiple antibodies are directed against the same antigen, protein, lipid, carbohydrate, etc. In some embodiments, the antibodies recruited are in IVIG. In some embodiments, IVIG may be administered before, simultaneously with, or after the agent or composition. Antibodies of various types of immunoglobulin structures, among others, may be recruited. In some embodiments, one or more subclasses of IgG are recruited.In some embodiments, the recruited antibodies comprise IgG1. In some embodiments, the recruited antibodies comprise IgG2. In some embodiments, the recruited antibodies comprise IgG3. In some embodiments, the recruited antibodies comprise IgG4. In some embodiments, the recruited antibodies are or comprise IgG1 and IgG2. In some embodiments, the recruited antibodies are or comprise IgG1, IgG2, and IgG4. In some embodiments, the recruited antibodies are or comprise IgG1, IgG2, IgG3, and IgG4. The recruited antibodies may interact with various types of receptors, for example, receptors expressed by various types of immune cells. In some embodiments, the recruited antibodies may effectively interact with various types of Fc receptors to provide desired immune activity. In some embodiments, the recruited antibodies may recruit immune cells. In some embodiments, the recruited antibodies may effectively interact with hFcγRIIIA. In some embodiments, the recruited antibodies may effectively interact with hFcγRIIIA on macrophages. In some embodiments, macrophages are recruited to provide ADCC and / or ADCP activity against a virus, e.g., SARS-CoV-2 virus, and / or cells infected thereby. In some embodiments, NK cells are recruited to provide immune activity. In some embodiments, the recruited antibody can effectively interact with hFcγRIIA. In some embodiments, the recruited antibody can effectively interact with hFcγRIIA on dendritic cells. In some embodiments, the antibody moiety in the agent of the present disclosure comprises one or more properties, structures, and / or activities of the recruited antibody described herein.

[0102] amino acid In some embodiments, provided compounds and agents may include one or more amino acid moieties, for example, in antibody binding moieties, linker moieties, etc. The amino acid moieties may be either naturally occurring amino acid or unnatural amino acid moieties. In some embodiments, the amino acid has the structure of formula AI: NH(R a1 )-L a1-C(R a2 )(R a3 )-L a2 -COOH AI or a salt thereof, wherein R a1 , R a2 and R a3 each independently represents -L a -R', or an amino acid side chain; L a1 and L a2 Each of the a and Each L a are independently a covalent bond or C1 to C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3~20 Alicyclic ring, C 6~20 an aryl ring, a 5-20 membered heteroaryl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1~30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1~30 Heteroaliphatic, C 6~30 Aryl, C6~30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6~30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, the amino acid residue, e.g., the amino acid residue of an amino acid having the structure of formula AI, is -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 In some embodiments, each amino acid residue of the peptide independently has the structure -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 It has the structure -CO-.

[0103] In some embodiments, the disclosure provides a derivative of an amino acid of formula AI, or a salt thereof. In some embodiments, the derivative is an ester. In some embodiments, the disclosure provides a derivative of an amino acid of formula NH(R a1)-L a1 -C(R a2 )(R a3 )-L a2 -COOR CT or a salt thereof, wherein R CT is R', and each other variable is independently as described herein, or a salt thereof. CT is R. In some embodiments, R CT is an optionally substituted aliphatic. In some embodiments, R CT is t-butyl.

[0104] In some embodiments, L a1 is a covalent bond. In some embodiments, the compound of formula AI has the structure NH(R a1 )-C(R a2 )(R a3 )-L a2 In some embodiments, L a2 is -CH2SCH2-.

[0105] In some embodiments, L a2 is a covalent bond. In some embodiments, the compound of formula AI has the structure NH(R a1 )-L a1 -C(R a2 )(R a3 In some embodiments, the amino acid residue is a compound of the formula -N(R a1 )-L a1 -C(R a2 )(R a3 In some embodiments, L a1 is -CH2CH2S-. In some embodiments, L a1 is -CH2CH2S-, where CH2 is NH(R a1 ) is attached to

[0106] In some embodiments, L a1 is a covalent bond, and L a2 is a covalent bond. In some embodiments, the compound of formula AI has the structure NH(Ra1 )-C(R a2 )(R a3 In some embodiments, the compound of formula AI is a compound of the structure NH(R a1 )-CH(R a2 In some embodiments, the compound of formula AI is a compound of the structure NH(R a1 )-CH(R a3 )-COOH. In some embodiments, the compound of formula AI has the structure NH—CH(R a2 )-COOH. In some embodiments, the compound of formula AI has the structure NH—CH(R a3 In some embodiments, the amino acid residue is a compound of the formula -N(R a1 )-C(R a2 )(R a3 In some embodiments, the amino acid residue has the structure -N(R a1 )-CH(R a2 In some embodiments, the amino acid residue has the structure -N(R a1 )-CH(R a3 In some embodiments, the amino acid residue has the structure -NH-CH(R a2 In some embodiments, the amino acid residue has the structure -NH-CH(R a3 )-CO- structure.

[0107] In some embodiments, L a is a covalent bond. In some embodiments, L a is an optionally substituted C 1~6 In some embodiments, L a is an optionally substituted C 1~6 In some embodiments, L is alkylene. a is -CH-. In some embodiments, L a is -CHCH-. In some embodiments, L a is -CH2CH2CH2-.

[0108] In some embodiments, La is a divalent optionally substituted C 1~20 In some embodiments, L is aliphatic, wherein one or more methylene units are independently replaced with -C(O)-, -N(R')-, -Cy-, and / or -O-. a is a divalent optionally substituted C 1~20 aliphatic, wherein one or more methylene units are independently replaced with -C(O)N(R')-, -Cy-, and -O-. a is a divalent optionally substituted C 1~20 is aliphatic, wherein two or more methylene units are independently replaced with -C(O)N(R')- and -Cy-, in addition to other optional replacements. In some embodiments, -Cy- is optionally substituted. In some embodiments, -Cy- is optionally substituted with an electron-withdrawing group as described herein. In some embodiments, -Cy- is substituted with one or more -F. In some embodiments, -Cy- is optionally substituted 1,3-phenylene. In some embodiments, -Cy- is optionally substituted 1,4-phenylene. In some embodiments, L a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] In some embodiments, L is or comprises a teeth, [ka] is or contains

[0109] In some embodiments, R' is R. In some embodiments, R a1 is R, and R is as described in this disclosure. In some embodiments, R a1 is R and R is methyl. In some embodiments, R a2 is R, and R is as described in this disclosure. In some embodiments, R a3 is R, and R is as described in this disclosure. In some embodiments, R a1 , R a2 , and R a3 Each of is independently R, where R is as described in this disclosure.

[0110] In some embodiments, R a1 is hydrogen. In some embodiments, R a1is a protecting group. In some embodiments, R a1 is -Fmoc. In some embodiments, R a1 is -Dde.

[0111] In some embodiments, R a1 , R a2 and R a3 each independently represents -L a -R'.

[0112] In some embodiments, R a2 is hydrogen. In some embodiments, R a3 is hydrogen. In some embodiments, R a1 is hydrogen and R a2 and R a3 At least one of R is hydrogen. a1 is hydrogen and R a2 and R a3 is hydrogen and the other is not hydrogen. a2 -L a -R and R a3 is —H. In some embodiments, R a3 -L a -R and R a2 is —H. In some embodiments, R a2 is -CH2-R, and R a3 is —H. In some embodiments, R a3 is -CH2-R, and R a2 is —H. In some embodiments, R a2 is R and R a3 is —H. In some embodiments, R a3 is R and R a2 is -H.

[0113] In some embodiments, R a2 -L a -R, where R is as described in this disclosure. In some embodiments, R a2 -L a -R, where R is C 3~30Alicyclic, C 5~30 aryl, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a2 -L a -R, where R is C 6~30 aryl and 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a2 is the side chain of an amino acid. In some embodiments, R a2 is the side chain of a standard amino acid.

[0114] In some embodiments, R a3 -L a -R, where R is as described in this disclosure. In some embodiments, R a3 -L a -R, where R is C 3~30 Alicyclic, C 5~30 aryl, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a3 -L a -R, where R is C 6~30 aryl and 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a3 is the side chain of an amino acid. In some embodiments, R a3 is the side chain of a standard amino acid.

[0115] In some embodiments, one or R a2 and R a3 is —H. In some embodiments, one or R a2 and R a3 -L a -R and L a is as described herein. In some embodiments, L a is not a covalent bond. a are independently and optionally replaced as described herein, such as, for example, with -C(O)-, -N(R')-, -O-, -C(O)-N(R')-, and / or -Cy-. In some embodiments, L a is or includes -C(O)-, -N(R')-, and -Cy-. In some embodiments, L a is or includes C(O)N(R')- and -Cy-. In some embodiments, -Cy- is substituted as described herein, and one or more substituents are independently electron-withdrawing groups.

[0116] In some embodiments, the amino acid side chain is R a2 or R a3 In some embodiments, the amino acid side chain is -L LG1 -L LG2 -L LG3 -L LG4 In some embodiments, the amino acid side chain is or comprises -L LG2 -L LG3 -L LG4 In some embodiments, the amino acid side chain is or comprises -L LG3 -L LG4 In some embodiments, the amino acid side chain is or comprises -L LG4 In some embodiments, such side chains are or include: [ka] In some embodiments, such side chains are: [ka] In some embodiments, such side chains are: [ka] In some embodiments, such side chains are: [ka] is.

[0117] In some embodiments, R is optionally substituted C 1~6 In some embodiments, R is an optionally substituted C 1~6 In some embodiments, R is alkyl. In some embodiments, R is -CH. In some embodiments, R is optionally substituted pentyl. In some embodiments, R is n-pentyl.

[0118] In some embodiments, R is a cyclic group. In some embodiments, R is an optionally substituted C 3~30 In some embodiments, R is cyclopropyl.

[0119] In some embodiments, R is an optionally substituted aromatic group and the amino acid residue of the amino acid of formula AI is Xaa A In some embodiments, R a2 or R a3is -CH2-R, where R is an optionally substituted aryl or heteroaryl group. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is phenyl. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is 4-trifluoromethylphenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, R is an optionally substituted 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is an optionally substituted 5-14 membered heteroaryl having 1-5 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, R is [ka] In some embodiments, R is an optionally substituted pyridinyl. In some embodiments, R is 1-pyridinyl. In some embodiments, R is 2-pyridinyl. In some embodiments, R is 3-pyridinyl. In some embodiments, R is [ka] is.

[0120] In some embodiments, R' is -COOH. In some embodiments, the compound and amino acid residue of the amino acid of formula AI is Xaa N is.

[0121] In some embodiments, R' is -NH2. In some embodiments, the compound of the amino acid residue of the amino acid of formula AI is Xaa P is.

[0122] In some embodiments, R a2 or R a3 is R, and R is a C 1~20In some embodiments, the compound of amino acid residues of the amino acid of formula AI is Xaa H In some embodiments, R is -CH3. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is n-propyl. In some embodiments, R is butyl. In some embodiments, R is n-butyl. In some embodiments, R is pentyl. In some embodiments, R is n-pentyl. In some embodiments, R is cyclopropyl.

[0123] In some embodiments, R a1 , R a2 , and R a3 and two or more of are R and taken together form an optionally substituted ring as described in this disclosure.

[0124] In some embodiments, R a1 and R a2 and R a3 One of them is R, and together they form R a1 forms an optionally substituted 3- to 6-membered ring with no additional ring heteroatoms other than the nitrogen atom to which it is attached. In some embodiments, the ring formed is a 5-membered ring, such as proline.

[0125] In some embodiments, R a2 and R a3 is R and taken together form an optionally substituted 3-6 membered ring as described in this disclosure. In some embodiments, R a2 and R a3 is R and taken together form an optionally substituted 3-6 membered ring having one or more nitrogen ring atoms. In some embodiments, R a2 and R a3 is R and together form an optionally substituted 3-6 membered ring having one and no more than one ring heteroatom, of which is a nitrogen atom. In some embodiments, the ring is a saturated ring.

[0126] In some embodiments, the amino acid is a natural amino acid. In some embodiments, the amino acid is an unnatural amino acid. In some embodiments, the amino acid is an alpha-amino acid. In some embodiments, the amino acid is a beta-amino acid. In some embodiments, the compound of formula AI is a natural amino acid. In some embodiments, the compound of formula AI is an unnatural amino acid.

[0127] In some embodiments, the amino acid comprises a hydrophobic side chain. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, L, M, F, Y, or W. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, L, M, or F. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, L, or M. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, or L. In some embodiments, the hydrophobic side chain is R, where R is C. 1~10 In some embodiments, R is C 1~10In some embodiments, R is alkyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is butyl. In some embodiments, R is pentyl. In some embodiments, R is n-pentyl. In some embodiments, the amino acid having a hydrophobic side chain is NHCH(CHCHCHCHCHCH)COOH. In some embodiments, the amino acid having a hydrophobic side chain is (S)-NHCH(CHCHCHCHCHCH)COOH. In some embodiments, the amino acid having a hydrophobic side chain is (R)-NHCH(CHCHCHCHCHCH)COOH. In some embodiments, the hydrophobic side chain is -CHR, and R is an optionally substituted phenyl. In some embodiments, R is phenyl. In some embodiments, R is phenyl substituted with one or more hydrocarbon groups. In some embodiments, R is 4-phenylphenyl. In some embodiments, an amino acid having a hydrophobic side chain is NHCH(CH-4-phenylphenyl)COOH. In some embodiments, an amino acid having a hydrophobic side chain is (S)-NHCH(CH-4-phenylphenyl)COOH. In some embodiments, an amino acid having a hydrophobic side chain is (R)-NHCH(CH-4-phenylphenyl)COOH.

[0128] In some embodiments, the amino acid comprises a positively charged side chain as described herein (e.g., at physiological pH). In some embodiments, such an amino acid comprises a basic nitrogen in its side chain. In some embodiments, such an amino acid is Arg, His, or Lys. In some embodiments, such an amino acid is Arg. In some embodiments, such an amino acid is His. In some embodiments, such an amino acid is Lys.

[0129] In some embodiments, the amino acid comprises a negatively charged side chain as described herein (e.g., at physiological pH). In some embodiments, the amino acid comprises -COOH in its side chain. In some embodiments, the amino acid is Asp. In some embodiments, the amino acid is Glu.

[0130] In some embodiments, the amino acid comprises a side chain comprising an aromatic group as described herein. In some embodiments, the amino acid is Phe, Tyr, Trp, or His. In some embodiments, the amino acid is Phe. In some embodiments, the amino acid is Tyr. In some embodiments, the amino acid is Trp. In some embodiments, the amino acid is His. In some embodiments, the amino acid is NH2-CH(CH2-4-phenylphenyl)-COOH. In some embodiments, the amino acid is (S)-NH2-CH(CH2-4-phenylphenyl)-COOH. In some embodiments, the amino acid is (R)-NH2-CH(CH2-4-phenylphenyl)-COOH.

[0131] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] In some embodiments, the amino acid is [ka] or a salt thereof. In some embodiments, provided compounds are [ka] In some embodiments, the present disclosure provides a polypeptide agent comprising one or more amino acid residues described in this disclosure.

[0132] Common ways to deliver various medications The agents of the present disclosure can generally be prepared or isolated by synthetic and / or semi-synthetic methods, or recombinant methods, according to the present disclosure. Specific techniques are described in the Examples. In some embodiments, polypeptide agents, such as cell receptor-binding partial peptide agents, can be prepared using biological expression systems. In some embodiments, the provided agents are synthetically prepared. In some embodiments, the provided agents are prepared using specific techniques described in WO2019 / 023501, the entire contents of which are incorporated herein by reference.

[0133] A variety of techniques (e.g., techniques for preparing antibody-drug conjugates) can be utilized to prepare MATE agents. In many such techniques, conjugation is not selective with respect to amino acid residue sites; the product composition typically contains a variety of different types of agents that may differ from one another with respect to the number of conjugated target binding moieties and / or conjugation sites. In some embodiments, the present disclosure provides techniques that can be utilized for selective conjugation of target binding moieties at specific amino acid residue sites.

[0134] In some embodiments, the present disclosure provides a method, comprising: contacting a first agent comprising a cell receptor binding portion linked to a first reactive group, optionally via a first linker, with a second agent comprising an antibody portion linked to a second reactive group, optionally via a second linker, wherein the first reactive group reacts with the second reactive group; forming a product drug comprising the cell receptor binding moiety and the antibody binding moiety, optionally via a linker.

[0135] In some embodiments, the present disclosure provides a method, comprising: contacting a first composition comprising a plurality of first agents each comprising a cell receptor binding portion independently and optionally linked to a first reactive group via a first linker moiety with a second composition comprising a plurality of second agents each comprising an antibody portion independently and optionally linked to a second reactive group via a second linker moiety; A method is provided in which a product composition is formed that includes a plurality of product agents, each independently comprising a cell receptor binding moiety and an antibody binding moiety, optionally via a linker.

[0136] In some embodiments, the first composition is a composition comprising a first agent described herein. In some embodiments, the second agent independently comprises a second reactive group. In some embodiments, the second composition is a composition comprising a plurality of agents described herein, wherein each cell receptor binding moiety is independently a reactive group described herein. In some embodiments, the second composition is an antibody composition, wherein the antibodies in the composition are not chemically modified. In some embodiments, the second composition is an IVIG preparation. In some embodiments, the product composition is a composition comprising a plurality of agents described herein, wherein each cell receptor binding moiety is independently a cell receptor binding moiety described herein.

[0137] In some embodiments, the cell receptor-binding moiety in the product drug is the cell receptor-binding moiety in the first drug. In some embodiments, the antibody moiety in the product drug is the antibody moiety in the second drug. In some embodiments, the second drug is an antibody drug, such as a monoclonal antibody, an antibody in a polyclonal antibody, an antibody in an IVIG preparation, etc. In some embodiments, the second reactive group is a functional group of an amino acid residue, such as -NH2 of Lys, -SH of Cys, etc. In some embodiments, the second reactive group is -NH2 of a Lys residue, for example, at a residue selected from the corresponding amino acid residues K246 and K248 of an IgG1 heavy chain, K251 and K253 and corresponding amino acid residues of an IgG2 heavy chain, and K239 and K241 and corresponding amino acid residues of an IgG4 heavy chain. In some embodiments, the present disclosure provides selective reaction at specific amino acid residues of the antibody moiety.

[0138] In some embodiments, the second reactive group is attached to the antibody moiety, optionally via a linker. In some embodiments, the second reactive group is attached to the antibody moiety via a linker. In some embodiments, the second reactive group is selectively linked to one or more specific positions of the antibody moiety, for example, one or more specific positions selected from the corresponding amino acid residues K246 and K248 of the IgG1 heavy chain, K251 and K253 of the IgG2 heavy chain, and K239 and K241 of the IgG4 heavy chain. In some embodiments, the present disclosure provides selective reaction at specific amino acid residues of the antibody moiety.

[0139] In some embodiments, the present disclosure provides agents comprising, each independently, an antibody-binding moiety that binds to an antibody drug, a reactive group, a cell receptor-binding moiety, and optionally one or more linker moieties linking such groups / moieties. In some embodiments, such agents are useful as reaction partners (e.g., a first agent) for conjugating a moiety of interest, e.g., a target-binding moiety, an antibody-containing drug (e.g., a second agent) to the reactive group (e.g., a second reactive group). In some embodiments, the present disclosure provides agents for conjugating a moiety of interest to an antibody moiety in various drugs or antibody drugs (e.g., monoclonal antibody drugs, polyclonal antibody drugs, antibody drugs in IVIG preparations, etc.). In some embodiments, the provided agents each comprise a cell receptor-binding moiety, a reactive group, an antibody-binding moiety, and optionally one or more linker moieties (linkers) linking such moieties. In some embodiments, the antibody binding moiety is part of a leaving group that is released upon contacting such an agent (e.g., a first agent) with an antibody moiety (e.g., a second agent) and reacting a reactive group of such agent (e.g., a first reactive group of the first agent) with a reactive group of the antibody moiety (e.g., a second reactive group of the second agent, such as -NH2 of a Lys residue of an antibody protein). In some embodiments, among other things, the provided techniques can provide improved conjugation efficiency, high selectivity, and / or fewer steps (in some cases, a single step) for the conjugation product agent. In some embodiments, the provided agent, e.g., the first agent, is a compound of formula RI, or a salt thereof: LG-RG-LRM-TBT, (RI) or a salt thereof, wherein LG is a group comprising an antibody binding moiety; RG is a reactive group, LRM is a linker, TBT is the cell receptor binding moiety.

[0140] In some embodiments, LG is or comprises an antibody binding moiety described herein and a linker connecting the antibody binding moiety and RG.

[0141] As used in this disclosure, a moiety generally refers to a portion of a molecule, e.g., the moiety in an ester RCOOR', where the alcohol moiety is RO-. In some embodiments, the drug portion (e.g., a targeted drug, a peptide drug, an antibody drug, etc.) retains one or all of the desired structural features, properties, functions, and / or activities of the compound. For example, in some embodiments, a cell receptor binding portion can bind to a target as its corresponding targeted binding agent, optionally in an equivalent manner. In some embodiments, a targeted drug portion maintains one or more desired structural features, properties, functions, and / or properties equivalent to that of its corresponding targeted drug. In some embodiments, an antibody drug portion maintains one or more desired structural features, properties, functions, and / or properties equivalent to that of its corresponding antibody drug (e.g., three-dimensional structure, antigen specificity, antigen binding ability, and / or immunological function, etc.). In some embodiments, the moiety of a drug (e.g., a targeting drug moiety, a peptide drug moiety, an antibody drug moiety, etc.) is a monovalent (in the case of a monovalent moiety), divalent (in the case of a divalent moiety), or polyvalent (in the case of a polyvalent moiety) radical of a drug, e.g., a targeting drug (in the case of a targeting drug moiety), a peptide drug (in the case of a peptide drug moiety), an antibody drug (in the case of an antibody drug moiety), etc. In some embodiments, a monovalent radical is formed by removing a monovalent moiety (e.g., another monovalent group such as hydrogen, halogen, alkyl, aryl, etc.) from the compound / drug. In some embodiments, a divalent or polyvalent radical is formed by removing one or more monovalent (e.g., a monovalent group such as hydrogen, halogen, alkyl, aryl, etc.), divalent, and / or polyvalent moieties from the compound / drug. In some embodiments, a radical is formed by removing a hydrogen atom. In some embodiments, the moiety is monovalent. In some embodiments, the moiety is divalent. In some embodiments, the moiety is polyvalent.

[0142] In some embodiments, LG is R LG -L LG- or contains R LG is or comprises an antibody binding moiety, and L LG is a linker moiety described herein. In some embodiments, LG is ABT-L LG In some embodiments, L LG -L LG1 -L LG2 - and L LG1 and L LG2 Each of L is independently a linker moiety described herein. LG -L LG1 -L LG2 -L LG3 - and L LG1 , L LG2 and L LG3 Each of L is independently a linker moiety described herein. LG -L LG1 -L LG2 -L LG3 -L LG4 - and L LG1 , L LG2 , L LG3 and L LG4 Each of L is independently a linker moiety described herein. LG1 is R LG In some embodiments, L LG1 is linked to a cell receptor binding moiety. LG -L LG1 - and the reactive group is L LG2 , L LG3 and L LG4 In some embodiments, L LG -L LG1 -L LG2 - and the reactive group is L LG3 and L LG4 In some embodiments, L LG -L LG1 -L LG2 -L LG3 - and the reactive group is L LG4 In some embodiments, L LG1 , LLG2 , L LG3 and L LG4 Each of is independently L as described herein.

[0143] In some embodiments, the antibody binding moiety, such as LG, is released after reaction, for example, after a first agent (e.g., where the MOI is the target binding moiety) reacts with a second agent (e.g., an antibody drug comprising a reactive amino acid residue, such as an amino group, as the second reactive group and / or a second agent comprising a second reactive group introduced into the antibody drug), or after a first agent (e.g., where the MOI is a reactive group, such as a second reactive group) reacts with a second agent that is an antibody drug. In some embodiments, the antibody binding moiety is released after reaction. In some embodiments, LG is released after reaction. In some embodiments, the leaving group is released as part of a compound having the structure LG-H or a salt thereof. In some embodiments, the antibody binding moiety is released as part of a compound having the structure LG-H or a salt thereof. In some embodiments, LG is released as part of a compound having the structure LG-H or a salt thereof. In some embodiments, the compound released is R LG -L LG1 -L LG2 -L LG3 -L LG4 In some embodiments, the antibody binding moiety has the structure R LG -L LG1 -L LG2 -L LG3 -L LG4 In some embodiments, the antibody binding moiety is released as part of a compound having the structure R LG -L LG1 -L LG2 -L LG3 -L LG4 -H or a salt thereof, and R LG is or comprises an antibody binding moiety. In some embodiments, LG is R LG -L LG1 -L LG2 -L LG3 -L LG4-H or a salt thereof, and LG is released as a part of a compound having the structure R LG -L LG and L LG -L LG1 -, -L LG1 -L LG2 -, -L LG1 -L LG2 -L LG3 - or -L LG1 -L LG2 -L LG3 -L LG4 In some embodiments, LG is R LG -L LG1 -L LG2 -L LG3 -L LG4 -H or a salt thereof, and LG is released as a part of a compound having the structure R LG -L LG1 In some embodiments, LG is R LG -L LG1 -L LG2 -L LG3 -L LG4 -H or a salt thereof, and LG is released as a part of a compound having the structure R LG -L LG1 -L LG2 In some embodiments, LG is R LG -L LG1 -L LG2 -L LG3 -L LG4 -H or a salt thereof, and LG is released as a part of a compound having the structure R LG -L LG1 -L LG2 -L LG3 In some embodiments, LG is R LG -L LG1 -L LG2 -L LG3 -L LG4 -H or a salt thereof, and LG is released as a part of a compound having the structure R LG -L LG1 -L LG2 -L LG3 -L LG4 is.

[0144] In some embodiments, L is a covalent bond or a divalent optionally substituted straight-chain or branched C alkyl group comprising one or more aliphatic moieties, aryl moieties, heteroaliphatic moieties each independently having 1 to 20 heteroatoms, heteroaromatic moieties each independently having 1 to 20 heteroatoms, or any combination of any one or more of such moieties. 1~100 is a group, wherein one or more methylene units of the group are optionally and independently selected from C 1~6 Alkylene, C 1~6 Alkenylene, divalent C with 1 to 5 heteroatoms 1~6 Heteroaliphatic group, -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')- , -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- , -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P( S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is replaced by a covalent bond or a divalent optionally substituted straight or branched C 1~100an aliphatic or heteroaliphatic group having 1 to 20 heteroatoms, wherein one or more methylene units of the group are optionally and independently selected from: -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR') -, -P(S)(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is a covalent bond or a divalent optionally substituted linear or branched C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C44, C55, C34, C35, C36, C37, C48, C56, C57, C58, C69, C70, C71, C72, C73, C74, C75, C76, C77, C78, ​​C79, C81, C82, C83, C84, C85, C86, C87, C88, C89, C91, C92, C93, C94, C95, C96, C97, C98, C99, C91 ...5, C96, C97, C98, C99, C99, C100, C99, C111, C99, C122, C99, C132, C99, C142, C99, C152, C99, C163, C99, C174, C185, C195, C196, C197, C198, C199, C199, C199, C199, C199, C101, 10 , C 15 , C 20 , C 25 , C 30 , C 40 , C 50 , C 60 , C 1~2 , C 1~5 , C 1~10 , C 1~15 , C 1~20 , C 1~30 , C 1~40 , C 1~50 , C 1~60 , C 1~70 , C 1~80 , or C 1~90an aliphatic or heteroaliphatic group having 1 to 10 heteroatoms, wherein one or more methylene units of the group are optionally and independently selected from the group consisting of -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O )2-, -S(O)2N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P( S)(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is a covalent bond or a divalent optionally substituted linear or branched C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C44, C55, C34, C35, C36, C37, C48, C56, C57, C58, C69, C70, C71, C72, C73, C74, C75, C76, C77, C78, ​​C79, C81, C82, C83, C84, C85, C86, C87, C88, C89, C91, C92, C93, C94, C95, C96, C97, C98, C99, C91 ...5, C96, C97, C98, C99, C99, C100, C99, C111, C99, C122, C99, C132, C99, C142, C99, C152, C99, C163, C99, C174, C185, C195, C196, C197, C198, C199, C199, C199, C199, C199, C101, 10 , C 15 , C 20 , C 25 , C 30 , C 40 , C 50 , C 60 , C 1~2 , C 1~5 , C 1~10 , C 1~15 , C 1~20 , C 1~30 , C 1~40 , C 1~50 , C 1~60 , C 1~70 , C 1~80 , or C 1~90an aliphatic or heteroaliphatic group having 1 to 10 heteroatoms, wherein one or more methylene units of the group are optionally and independently selected from -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, -C(O)O-, an amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is a covalent bond or a divalent optionally substituted linear or branched C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C40, C51, C52, C53, C54, C55, C56, C57, C58, C59, C69, C69, C69, C70, C71, C72, C73, C74, C75, C76, C77, C78, ​​C79, C80, C81, C82, C83, C84, C85, C86, C87, C88, C89, C91, C92, C93, C94, C95, C96, C97, C98, C99, C91 ...5, C96, C97, C98, C99, C99, C100, C99, C111, C99, C122, C99, C133, C99, C143, C99, C152, C163, C174, C185, C195, C196, C197, C198, C199, C 10 , C 15 , C 20 , C 25 , C 30 , C 40 , C 50 , C 60 , C 1~2 , C 1~5 , C 1~10 , C 1~15 , C 1~20 , C 1~30 , C 1~40 , C 1~50 , C 1~60 , C 1~70 , C 1~80 , or C 1~90 is an aliphatic group, wherein one or more methylene units of the group are optionally and independently selected from -O-, -N(R')-, -C(O)-, -C(O)N(R')-, -C(O)C(R')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)N(R')-, an amino acid residue, or -[(-OC(R')-C(R')-) n In some embodiments, L is a covalent bond or a divalent optionally substituted linear or branched C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C40, C51, C52, C53, C54, C55, C56, C57, C58, C59, C69, C69, C69, C70, C71, C72, C73, C74, C75, C76, C77, C78, ​​C79, C80, C81, C82, C83, C84, C85, C86, C87, C88, C89, C91, C92, C93, C94, C95, C96, C97, C98, C99, C91 ...5, C96, C97, C98, C99, C99, C100, C99, C111, C99, C122, C99, C133, C99, C143, C99, C152, C163, C174, C185, C195, C196, C197, C198, C199, C 10 , C 15 , C 20 , C 25 , C 30 , C40 , C 50 , C 60 , C 1~2 , C 1~5 , C 1~10 , C 1~15 , C 1~20 , C 1~30 , C 1~40 , C 1~50 , C 1~60 , C 1~70 , C 1~80 , or C 1~90 is an aliphatic group, wherein one or more methylene units of the group are optionally and independently -O-, -N(R')-, -C(O)-, -C(O)N(R')-, -C(O)C(R')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)N(R')-, or -[(-OC(R')-C(R')-) n In some embodiments, L is replaced by a covalent bond or a divalent optionally substituted straight or branched C 1~10 is an aliphatic group, wherein one or more methylene units of the group are optionally and independently -O-, -N(R')-, -C(O)-, -C(O)N(R')-, -C(O)C(R')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)N(R')-, -Cy-, or -[(-OC(R')-C(R')-) n In some embodiments, L is replaced by a covalent bond or a divalent optionally substituted straight or branched C 1~10 is an aliphatic group, wherein one or more methylene units of the group are optionally and independently -O-, -N(R')-, -C(O)-, -C(O)N(R')-, -C(O)C(R')N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)N(R')-, or -[(-OC(R')-C(R')-) n]- (wherein n is 1 to 10). In some embodiments, L does not contain -C(O)O-. In some embodiments, L does not contain -C(O)-N(R')-. In some embodiments, L does not contain -S-. In some embodiments, L does not contain -S-Cy-. In some embodiments, L does not contain -SS-. In some embodiments, L does not contain one or more, or any, of -C(O)O-, -C(O)-N(R')-, -S-, and -SS-. In some embodiments, L does not contain one or more, or any, of -C(O)O-, -C(O)-N(R')-, -S-Cy-, and -SS-. In some embodiments, L does not contain one or more, or any, of -C(O)O-, -C(O)-N(R')-, -S-Cy-, and -SS-. In some embodiments, L does not contain one or more, or any, of -C(O)O-, -S-Cy-, and -SS-. In some embodiments, L does not contain any of -C(O)O-, -S-, and -SS-. In some embodiments, L does not contain any of -C(O)O-, -S-Cy-, and -SS-. In some embodiments, L does not contain any of -C(O)O- and -SS-.

[0145] In some embodiments, L is a covalent bond. In some embodiments, L is not a covalent bond.

[0146] In some embodiments, L LG1 is a covalent bond. In some embodiments, L LG1 is not a covalent bond. LG1 In some embodiments, L is or includes -(CHCHO)-. LG1 is or includes -(CH2)nO-(CH2CH2O)n-(CH2)n-, where each n is independently as described herein and each -CH2- is independently optionally substituted. In some embodiments, L LG1is —(CH)O—(CHCHO)—(CH)—, where each n is independently as described herein and each —CH— is independently optionally substituted. In some embodiments, L LG1 is —(CH)—O—(CHCHO)—(CH)—, where n is as described herein, and each —CH— is independently optionally substituted. In some embodiments, L LG1 is —(CH 2 ) 2 —O—(CH 2 CH 2 O) n —(CH 2 ) 2 —, where n is as described herein.

[0147] In some embodiments, L LG1 is -CH-. In some embodiments, L LG1 is —(CH)—. In some embodiments, L LG1 is —(CH)—C(O)—. In some embodiments, L LG1 is —(CH)—C(O)—NH—. In some embodiments, L LG1 is —(CH)—. In some embodiments, L LG1 is —(CH 2 ) 3 NH—. In some embodiments, L LG1 is —(CH)NH—C(O)—. In some embodiments, L LG1 is —C(O)—(CH)NH—C(O)—. In some embodiments, L LG1 is —C(O)—(CH)—. In some embodiments, L LG1 is —NH—C(O)—(CH)—. In some embodiments, L LG1 is -NHC(O)-(CH2)3NH-C(O)-. In some embodiments, -CH2- is attached to the antibody binding moiety.

[0148] In some embodiments, L LG1 is —CH2CH2—O—CH2CH2—O—CH2CH2—. In some embodiments, L LG1 is —CH2CH2—O—CH2CH2—O—CH2CH2—C(O)—. In some embodiments, LLG1 is —CH2CH2—O—CH2CH2—O—CH2CH2—C(O)NH—. In some embodiments, L LG1 is -CH2CH2-O-CH2CH2-O-CH2CH2-C(O)NH-CH2-. In some embodiments, -CH2CH2- is attached to the antibody binding moiety.

[0149] In some embodiments, L LG1 is —(CH2CH2O)n—. In some embodiments, L LG1 is —(CH2CH2O)n-CH2-CH2-. In some embodiments, L LG1 is —(CH2CH2O)n-CH2-CH2-C(O)—. In some embodiments, L LG1 is —(CH2CH2O)2—CH2—CH2—C(O)—. In some embodiments, L LG1 is —(CH2CH2O)4—CH2—CH2—C(O)—. In some embodiments, L LG1 is -(CH2CH2O)8-CH2-CH2-C(O)-. In some embodiments, -C(O)- is attached to the antibody binding moiety.

[0150] In some embodiments, L LG1 is -N(R')-. In some embodiments, L LG1 In some embodiments, L LG1 is -NH-[(-CHCH-O-)]-. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—. In some embodiments, L LG1 is -NH-[(-CH2CH2-O-)]n-CH2CH2-NH-C(O)-. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, L LG1is —NH—CHCH—O—. In some embodiments, L LG1 is —NH—CH2CH2—O—CH2CH2—. In some embodiments, L LG1 is —NH—CHCH—O—CHCH—NH—. In some embodiments, L LG1 is -NH-CH2CH2-O-CH2CH2-NH-C(O)-.

[0151] In some embodiments, L LG1 is -NH-[(-CHCH-O-)]-. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—C(O)—.

[0152] In some embodiments, L LG1 is -NH-[(-CHCH-O-)]-. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—C(O)—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—NH—C(O)—. In some embodiments, L LG1is -NH-[(-CHCH-O-)]-. In some embodiments, L LG1 is —NH—[(—CHCH—O—)]—CHCH—. In some embodiments, L LG1 is -NH-[(-CHCH-O-)]-CHCH-NH-. In some embodiments, L LG1 is -NH-[(-CH2CH2-O-)]5-CH2CH2-NH-C(O)-. In some embodiments, -NH- is attached to the antibody binding moiety.

[0153] In some embodiments, L LG1 is -CH-. In some embodiments, L LG1 is -CHCH-. In some embodiments, L LG1 is —CH2CH2NH—. In some embodiments, L LG1 is —CH 2 CH 2 NH—(CO)—. In some embodiments, —CH 2 — is attached to the antibody binding moiety.

[0154] In some embodiments, L LG1 is -CH-. In some embodiments, L LG1 is —CHC(O)—. In some embodiments, L LG1 is —CHC(O)NH—. In some embodiments, L LG1 is —CH 2 (CO)NHCH 2 —. In some embodiments, —CH 2 —C(O)— is attached to the antibody binding moiety at —CH 2 —.

[0155] In some embodiments, L LG2 is a covalent bond. In some embodiments, L LG2 is not a covalent bond. LG2 is —N(R′)C(O)—. In some embodiments, L LG2 is —NHC(O)—. In some embodiments, L LG2 is —(CH)N(R′)C(O)—, where —(CH)— is optionally substituted. In some embodiments, L LG2is —(CH)—OC(O)—, where —(CH)— is optionally substituted. In some embodiments, L LG2 is —(CH)—OC(O)N(R′)—, where —(CH)— is optionally substituted. In some embodiments, L LG2 is -(CH2)n-OC(O)NH-, where -(CH2)n- is optionally substituted. In some embodiments, n is 1 to 10, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, -(CH2)n- is substituted. In some embodiments, -(CH2)n- is unsubstituted. In some embodiments, L LG2 is —CHN(CHCHCHS(O)OH)—C(O)—. In some embodiments, L LG2 is —C(O)—NHCH—. In some embodiments, L LG2 is —C(O)—NHCH2CH2—. In some embodiments, L LG2 is —C(O)O—CH—. In some embodiments, L LG2 is -NH-C(O)O-CH-. In some embodiments, -C(O)- is L LG3 In some embodiments, the -N(R')-, -NH-, or optionally substituted -CH2- unit (of optionally substituted -(CH2)n-) is bonded to L LG3 In some embodiments, L LG2 is -NH-, -NHC(O)-, -(CH)-NHC(O)-, -(CH)-OC(O)-, -(CH)-OC(O)NH-, -C(O)-NHCH-, -C(O)-NHCHCH-, -C(O)O-CH-, or -NH-C(O)O-CH-.

[0156] In some embodiments, L LG2 is -N(R')-. In some embodiments, L LG2 is -N(R)-. In some embodiments, L LG2is -NH-.

[0157] In some embodiments, L LG2 is an optionally substituted divalent C 1~6 In some embodiments, L LG2 is -CH-. In some embodiments, L LG2 is —CHNH—. In some embodiments, L LG2 is —CHNH—C(O)—. In some embodiments, L LG2 is -CH2NH-C(O)-CH2-.

[0158] In some embodiments, L LG3 is or includes an optionally substituted aryl ring. In some embodiments, L LG3 is or includes an optionally substituted phenyl ring. In some embodiments, L LG3is a phenyl ring substituted with one or more electron-withdrawing groups. As will be appreciated by one of ordinary skill in the art, a variety of electron-withdrawing groups are known in the art and may be utilized in accordance with the present disclosure. In some embodiments, the electron-withdrawing group is a halogen. In some embodiments, the electron-withdrawing group is -F. In some embodiments, the electron-withdrawing group is -Cl. In some embodiments, the electron-withdrawing group is -Br. In some embodiments, the electron-withdrawing group is -I. In some embodiments, the electron-withdrawing group comprises an X=Y double bond, where X is bonded to a group to which the electron-withdrawing group is a substituent, and at least one of X and Y is a heteroatom. In some embodiments, X is a heteroatom. In some embodiments, Y is a heteroatom. In some embodiments, each of X and Y is independently a heteroatom. In some embodiments, Y is O. In some embodiments, Y is S. In some embodiments, X is C. In some embodiments, X is N. In some embodiments, X is P. In some embodiments, X is S. In some embodiments, X=Y is C=O. In some embodiments, X=Y is N=O. In some embodiments, X=Y is S=O. In some embodiments, X=Y is P=O. In some embodiments, the electron withdrawing group is -C(O)-L-R'. In some embodiments, the electron withdrawing group is -C(O)-R'. In some embodiments, it is -NO2. In some embodiments, it is S(O)-L-R'. In some embodiments, it is -S(O)-R'. In some embodiments, it is -S(O)-L-R'. In some embodiments, it is -S(O)-O-R'. In some embodiments, it is -S(O)-N(R')2. In some embodiments, it is -P(O)(-L-R')2. In some embodiments, it is -P(O)(R')2. In some embodiments, it is -P(O)(OR')2. In some embodiments, it is -P(O)[N(R')2]2.

[0159] In some embodiments, L LG3 -L LG3a -L LG3b - and L LG3ais a covalent bond or —C(O)O—CH—, where —CH— is optionally substituted; L LG3b is an optionally substituted aryl ring. In some embodiments, L LG3a L LG2 is bonded to L LG3b L LG4 is connected to

[0160] In some embodiments, L LG3a is a covalent bond. In some embodiments, L LG3a is —C(O)O—CH—, where —CH— is optionally substituted. In some embodiments, L LG3a is —C(O)O—CH—, wherein —CH— is substituted. LG3a is —C(O)O—CH—, where —CH— is unsubstituted.

[0161] In some embodiments, the first group, the antibody binding moiety, and / or LG is R LG -L LG1 -L LG2 It is released as part of a compound having the structure —H or a salt thereof.

[0162] In some embodiments, L LG3b is an optionally substituted phenyl ring. In some embodiments, at least one substituent is an electron-withdrawing group as described herein.

[0163] In some embodiments, L LG3 teeth, [ka] s is 0 to 4, and each R s are independently halogen, -NO2, -L-R', -C(O)-L-R', -S(O)-L-R', -S(O)2-L-R', or -P(O)(-L-R')2. LG4 In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] is.

[0164] In some embodiments, L LG3b teeth, [ka] wherein s is 0 to 4, and each R s are independently halogen, -NO2, -L-R', -C(O)-L-R', -S(O)-L-R', -S(O)2-L-R', or -P(O)(-L-R')2. LG4 In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] is.

[0165] In some embodiments, s is 0. In some embodiments, s is 1-4. In some embodiments, s is 1. In some embodiments, s is 2. In some embodiments, s is 3. In some embodiments, s is 4.

[0166] In some embodiments, s is 1 to 4 and at least one R s is an electron withdrawing group, such as an electron withdrawing group as described above. In some embodiments, at least R s is —NO. In some embodiments, at least one R s is -F. In some embodiments, each R s is independently an electron-withdrawing group. s is —NO. In some embodiments, each R s is -F.

[0167] In some embodiments, the electron withdrawing group or R s is at C2. In some embodiments, an electron withdrawing group or R s is at C3. In some embodiments, an electron withdrawing group or Rs is at C4. In some embodiments, an electron withdrawing group or R s are in C2 and C5.

[0168] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] In some embodiments, L LG3 teeth, [ka] is.

[0169] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] In some embodiments, L LG3b teeth, [ka] is.

[0170] In some embodiments, L LG3b is optionally substituted [ka] In some embodiments, the nitrogen atom is —O—. LG4 In some embodiments, the nitrogen atom is bonded to L, which is —O—. LG4 is connected to -L RG1 -L RG2 - is -C(O)-.

[0171] In some embodiments, -L LG4 -L RG1 -L RG2 - is -OC(O)-. In some embodiments, -L LG4 -L RG1 -L RG2 - is -SC(O)-.

[0172] In some embodiments, L LG4 is a covalent bond. In some embodiments, L LG4 is not a covalent bond. LG4 is —O—. In some embodiments, L LG4 is -N(R')-. In some embodiments, L LG4 In some embodiments, L LG4 is —N(CH)—. In some embodiments, L LG4 is -N(R')-, and L LG3 In some embodiments, R' is an optionally substituted C 1~6 In some embodiments, L LG4 is -S-.

[0173] As described herein, in some embodiments, R LG is or comprises an antibody binding moiety. In some embodiments, R LG is or comprises a protein-binding moiety. In some embodiments, R LG is or comprises an antibody binding moiety. In some embodiments, R LG is an antibody binding moiety. In some embodiments, R LG is a protein-binding moiety. In some embodiments, R LG is the antibody binding moiety.

[0174] In some embodiments, R LG teeth, [ka] , R c -(Xaa)z-, a nucleic acid moiety, or a small molecule moiety. LG is described herein [ka] In some embodiments, R LG is the R c In some embodiments, R is or comprises -(Xaa)z-. LG is or comprises a small molecule moiety. In some embodiments, R LG is or comprises a peptide drug. In some embodiments, R LG is or comprises a nucleic acid drug. LG In some embodiments, the antibody binding moiety is or comprises an aptamer drug as described herein. [ka] In some embodiments, the protein-binding moiety is or comprises the [ka] In some embodiments, the antibody binding moiety is or comprises [ka] In some embodiments, the antibody binding moiety is or comprises R as described herein. c In some embodiments, the protein-binding moiety is or comprises -(Xaa)z-. c In some embodiments, the antibody binding moiety is or comprises an R as described herein. c is or contains -(Xaa)z-;

[0175] In some embodiments, in accordance with the present disclosure, the target binding moiety may be conjugated to the antibody moiety via a linker moiety, optionally utilizing the technology described in US2020 / 0190165.

[0176] In some embodiments, specific protecting groups ("PG"), leaving groups ("LG"), or transformation conditions are shown; one of skill in the art will recognize that other protecting groups, leaving groups, and transformation conditions are also suitable and contemplated. Such groups and transformations are discussed in detail in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, M.B. Smith and J. March, 5 th Edition,John Wiley & Sons,2001,Comprehensive Organic Transformations,RCLarock,2 nd Edition,John Wiley & Sons,1999,and Protecting Groups in Organic Synthesis,TWGreene and PGMWuts,3 rd edition, John Wiley & Sons, 1999, each of which is incorporated herein by reference in its entirety.

[0177] In some embodiments, leaving groups include, but are not limited to, halogens (e.g., fluoride, chloride, bromide, iodide), sulfonates (e.g., mesylate, tosylate, benzenesulfonate, brosylate, nosylate, trifluoromethanesulfonate), diazonium, and the like.

[0178] In some embodiments, oxygen protecting groups include, for example, carbonyl protecting groups, hydroxyl protecting groups, etc. Hydroxyl protecting groups are well known in the art and are described in Protecting Groups in Organic Synthesis, T.W. Greene and P.G.M.Wuts, 3 rdedition, John Wiley & Sons, 1999, the entire contents of which are incorporated herein by reference. Examples of suitable hydroxyl protecting groups include, but are not limited to, esters, allyl ethers, ethers, silyl ethers, alkyl ethers, arylalkyl ethers, and alkoxyalkyl ethers. Examples of such esters include formates, acetates, carbonates, and sulfonates. Specific examples include formate, benzoylformate, chloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate, 4,4-(ethylenedithio)pentanoate, pivalate (trimethylacetyl), crotonate, 4-methoxy-crotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate, carbonate (e.g., methyl, 9-fluorenylmethyl, ethyl, 2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, 2-(phenylsulfonyl)ethyl, vinyl, allyl, and p-nitrobenzyl). Examples of such silyl ethers include trimethylsilyl ether, triethylsilyl ether, t-butyldimethylsilyl ether, t-butyldiphenylsilyl ether, triisopropylsilyl ether, and other trialkylsilyl ethers. Alkyl ethers include methyl ether, benzyl ether, p-methoxybenzyl ether, 3,4-dimethoxybenzyl ether, trityl ether, t-butyl ether, allyl ether, and allyloxycarbonyl ether or derivatives. Alkoxyalkyl ethers include acetals such as methoxymethyl ether, methylthiomethyl ether, (2-methoxyethoxy)methyl ether, benzyloxymethyl ether, β-(trimethylsilyl)ethoxymethyl ether, and tetrahydropyranyl ether.Examples of arylalkyl ethers include benzyl ether, p-methoxybenzyl (MPM) ether, 3,4-dimethoxybenzyl ether, O-nitrobenzyl ether, p-nitrobenzyl ether, p-halobenzyl ether, 2,6-dichlorobenzyl ether, p-cyanobenzyl ether, and 2- and 4-picolyl ethers.

[0179] Amino protecting groups are well known in the art and are described in Protecting Groups in Organic Synthesis, T.W. Greene and P.G.M. Butts, 3 rd edition, John Wiley & Sons, 1999, the entire contents of which are incorporated herein by reference. Suitable amino-protecting groups include, but are not limited to, aralkylamines, carbamates, cyclic imides, allylamines, amides, and the like. Examples of such groups include t-butyloxycarbonyl (BOC), ethyloxycarbonyl, methyloxycarbonyl, trichloroethyloxycarbonyl, allyloxycarbonyl (Alloc), benzyloxycarbonyl (CBZ), allyl, phthalimide, benzyl (Bn), fluorenylmethylcarbonyl (Fmoc), formyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, phenylacetyl, trifluoroacetyl, benzoyl, and the like.

[0180] Those skilled in the art will understand that the provided agents may contain one or more stereocenters and may exist as racemic or diastereomeric mixtures. Those skilled in the art will also understand that there are many methods known in the art for the separation of isomers to obtain stereochemically enriched or stereochemically pure isomers of those compounds, including, but not limited to, HPLC, chiral HPLC, fractional crystallization of diastereomeric salts, kinetic enzymatic resolution (e.g., lipases or esterases of fungal, bacterial, or animal origin), and the formation of covalent diastereomeric derivatives using enantioenriched reagents.

[0181] Those skilled in the art will understand that various functional groups present in the compounds of the present disclosure, such as aliphatic groups, alcohols, carboxylic acids, esters, amides, aldehydes, halogens, and nitriles, can be interconverted by techniques well known in the art, including, but not limited to, reduction, oxidation, esterification, hydrolysis, partial oxidation, partial reduction, halogenation, dehydration, partial hydration, and hydration. See "March's Advanced Organic Chemistry," 5 th Ed., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001, which is incorporated herein by reference in its entirety. Such interconversions may require one or more of the techniques described above, and specific methods for synthesizing compounds of the disclosure are described in the Examples below.

[0182] As will be appreciated by those skilled in the art, the reaction partners are generally contacted with one another under conditions and for a time sufficient to produce a desired result, e.g., to form a product drug and compositions thereof to the desired extent. Many reaction conditions / reaction times may be evaluated and utilized in accordance with the present disclosure, provided they are suitable for the desired purpose; specific such conditions, reaction times, evaluations, etc. are described in the Examples.

[0183] In some embodiments, the drug formed, e.g., the product MATE drug, has a structure of formula M-I or M-II, or a salt thereof. In some embodiments, the cell receptor binding moiety in the product drug (e.g., a MATE drug) is the same as the cell receptor binding moiety in the reaction partner (e.g., a first drug comprising the cell receptor binding moiety) utilized to prepare the product drug. In some embodiments, the antibody moiety in the product drug (e.g., a MATE drug) is the same as the antibody moiety in the reaction partner (e.g., a second drug comprising the antibody moiety) utilized to prepare the product drug.

[0184] In some embodiments, the linker moiety (or a portion thereof) connected to the target binding moiety and / or antibody moiety is a linker moiety that is linked to a reactive partner (e.g., L of formula RI) RM or a salt thereof). In some embodiments, the linker moiety (L PM (e.g., L in formula M-I or M-II) refers to a linker moiety (e.g., between a reactive group and a cell receptor binding moiety, e.g., L RM In some embodiments, L PM L RM In some embodiments, L is or comprises PM -L RM -L RG2 In some embodiments, L RG2 is —C(O)—. In some embodiments, L RG2 is —C(O)— and is attached to —NH— of the targeting agent moiety, e.g., —NH— in the side chain of a lysine residue of the protein moiety, which in some embodiments is an antibody moiety.

[0185] The reactive partner, e.g., a compound of Formula RI or a salt thereof, typically does not contain a moiety capable of reacting with the reactive group under conditions in which the reactive group reacts with a targeting drug. In some embodiments, to the extent that some moieties in the reactive partner are capable of reacting with the reactive group under conditions in which the reactive group reacts with a targeting drug, the reaction between such moieties and the reactive group is significantly slower and / or less efficient than the reaction between the reactive group and the targeting drug. In some embodiments, the reaction between such moieties and the reactive group does not significantly reduce the efficiency, yield, rate, and / or conversion rate, etc., of the reaction between the reactive group and the targeting drug (e.g., by no more than about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, etc.). In some embodiments, the reactive group (e.g., an ester group, an activated carboxylic acid derivative, etc.) reacts with an amino group (e.g., an —NH group) of a targeting drug (e.g., a protein drug such as an antibody drug). In some embodiments, the reaction partner, e.g., a compound of formula RI or a salt thereof, does not contain an amine group. In some embodiments, a compound of formula RI or a salt thereof (or a portion thereof, e.g., R LG , L LG , L LG1 , L LG2 , L LG3 , L LG4 , L RG1 , L RG2 , L RM , and / or MOI) do not contain amine groups. In some embodiments, they do not contain primary amine groups (—NH). In some embodiments, they do not contain —CHNH. In some embodiments, they do not contain —CHCHNH. In some embodiments, they do not contain —CHCHCHNH. In some embodiments, they do not contain —CHCHCHCHNH. In some embodiments, they do not contain —CHCHCHCHNH. In some embodiments, amine groups, e.g., primary amine groups, are capped (e.g., by introduction of an acyl group (e.g., RC(O)— (e.g., acetyl)) to form an amide group) to prevent or reduce undesired reactions.

[0186] In some embodiments, the reaction is carried out in a buffer system. In some embodiments, the buffer system of the present disclosure maintains the structure and / or function of the targeting agent, cell receptor binding moiety, etc. In some embodiments, the buffer is a phosphate buffer. In some embodiments, the buffer is a PBS buffer. In some embodiments, the buffer is a borate buffer. In some embodiments, the buffer of the present disclosure provides, and optionally maintains, a specific pH value or range. For example, in some embodiments, a useful pH is about 7-9, e.g., 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 9.0, etc. In some embodiments, the pH is 7.4. In some embodiments, the pH is 7.5. In some embodiments, the pH is 7.8. In some embodiments, the pH is 8.0. In some embodiments, the pH is 8.2. In some embodiments, the pH is 8.3.

[0187] The provided technology can offer various advantages. Notably, in some embodiments, the connection of a cell receptor-binding moiety in a reaction partner (e.g., a compound comprising a reactive group located between the antibody-binding moiety and the cell receptor-binding moiety (e.g., a compound of formula RI or a salt thereof)) to a drug comprising an antibody moiety (e.g., a second drug such as an antibody drug), and the release of the antibody-binding moiety in the provided reaction partner can be accomplished in one reaction and / or one pot. Thus, in many embodiments, a separate reaction / step to remove the antibody-binding moiety is not performed. As will be appreciated by those skilled in the art, by performing the attachment of the cell receptor binding moiety and the release of the antibody-binding moiety in a single reaction / operation, the provided techniques can avoid a separate step for antibody-binding moiety removal, improving overall efficiency (e.g., by simplifying the operation, increasing overall yield, etc.), reducing production costs, and improving product purity (e.g., by avoiding exposure to antibody-binding moiety removal conditions, which typically involve one or more of conditions such as reduction, oxidation, hydrolysis (e.g., ester groups), etc., and which may damage the target drug moiety (e.g., protein drug moiety, protein amino acid residues, overall structure, and / or post-translational modifications (e.g., glycans of an antibody)). In some embodiments, among other things, the provided techniques can provide improved efficiency (e.g., in terms of reaction rate and / or conversion percentage), increased yield, increased purity / homogeneity, and / or enhanced selectivity, especially compared to reference techniques in which reaction partners that do not contain the antibody-binding moiety are used and which do not introduce a step for antibody-binding moiety removal (e.g., in which the antibody-binding moiety is removed in the same step as cell receptor binding moiety conjugation).

[0188] In some embodiments, the present disclosure provides, inter alia, products of the provided processes that include a lower level of damage to the antibody moiety compared to processes that include steps performed for the removal of the antibody-binding moiety but not for the substantial conjugation of the moiety of interest (e.g., target-binding moiety). In some embodiments, the provided product drug compositions have a higher degree of uniformity (e.g., with respect to the number of cell receptor-binding moieties per antibody moiety and / or the position of the amino acid residue in the antibody moiety conjugated to the moiety of interest) compared to a reference product composition (e.g., from a technology that does not use an antibody-binding moiety or that utilizes an additional step for antibody-binding moiety removal (e.g., that does not utilize a reaction partner described herein that includes a reactive group located between the antibody-binding moiety and the cell receptor-binding moiety)).

[0189] In some embodiments, the present disclosure provides product drugs that are drugs comprising an antibody portion, a cell receptor binding portion, and optionally a linker portion connecting the antibody binding portion and the cell receptor binding portion, hi some embodiments, the present disclosure provides compositions of such drugs.

[0190] In some embodiments, the present disclosure provides a composition comprising multiple agents, each agent independently: an antibody portion; and a cell receptor binding portion; Optionally, a linker moiety connecting the antibody-binding moiety and the cell receptor-binding moiety is provided.

[0191] In some embodiments, the product drug is a MATE drug. In some embodiments, the antibody drug portion comprises an IgG Fc region. In some embodiments, the antibody portion is connected to the cell receptor binding portion through an amino group, optionally via a linker. In some embodiments, it is through a lysine residue whose side chain amino group is connected to the cell receptor binding portion (e.g., as part of an amide group, carbamate group, etc., to form -NH-C(O)), optionally via a linker.

[0192] In some embodiments, selected positions of the antibody moiety are utilized for conjugation, for example, in some embodiments, K246 or K248 (EU numbering, or corresponding residues) of an antibody agent is a conjugation position. In some embodiments, the conjugation position is K246 of the heavy chain (unless otherwise specified, positions herein include, for example, the corresponding residue in a modified sequence (e.g., a longer, shorter, rearranged, etc. sequence). In some embodiments, the position is K248 of the heavy chain. In some embodiments, the position is K288 or K290 of the heavy chain. In some embodiments, the position is K288 of the heavy chain. In some embodiments, the position is K290 of the heavy chain. In some embodiments, the position is K317. In some embodiments, the antibody moiety is a portion of an IgG1 antibody or fragment thereof. In some embodiments, the antibody moiety is a portion of an IgG2 antibody or fragment thereof. In some embodiments, the antibody moiety is a portion of an IgG4 antibody or fragment thereof. In some embodiments, the composition comprises multiple MATE agents, and the antibody moieties of the multiple MATE agents are independently antibody moieties of an IgG1, IgG2, or IgG4 antibody, or fragment thereof.

[0193] In some embodiments, the antibody heavy chain is selectively conjugated / labeled over the light chain.

[0194] Among other things, the present disclosure can provide controlled cell receptor binding moiety (e.g., cell receptor binding moiety) / antibody moiety ratios (e.g., when the cell receptor binding moiety is a peptide cell receptor binding moiety, peptide cell receptor binding moiety / antibody ratio (PAR)). In some embodiments, the ratio is from about 0.1 to 10, 0.5 to 6, etc., e.g., about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, or 0.9 to about 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 12.0, 13.0, 14.0, 15.0, 16.0, 17.0, 18.0, 19.0, 21.0, 22.0, 23.0, 24.0, 25.0, 26.0, 27.0, 28.0, 29.0, 29.0, 30.0, 31.0, 32.0, 33.0, 34.0, 35.0, 36.0, 37.0, 38.0, 39.0, 40.0, 41.0, 42.0, 0.5, 6, 7, 8, 9, 10, about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6, 7, 8, 9, 10, etc.). In some embodiments, the ratio is the ratio of moiety of interest conjugated to the antibody moiety to the antibody moiety conjugated to the moiety of interest (e.g., when the ratio is in the context of a ratio of drugs). In some embodiments, the ratio is the ratio of moiety of interest conjugated to the antibody moiety to total antibody in a composition (e.g., when the ratio is in the context of a ratio of a composition). In some embodiments, the ratio is about 0.1 to 6. In some embodiments, the ratio is about 0.5 to 2.5. In some embodiments, the ratio is about 0.5 to 2. In some embodiments, the ratio is about 1 to 2. In some embodiments, the ratio is about 1.5 to 2. In some embodiments, the ratio is about 1.5 to 2 for IgG1, IgG2, and / or IgG4 antibodies or fragments thereof. In some embodiments, for compositions, e.g., target binding moieties conjugated to IVIG, the ratio is about 1.5 to 2.5. In some embodiments, the ratio is about 0.1. In some embodiments, the ratio is about 0.2. In some embodiments, the ratio is about 0.3. In some embodiments, the ratio is about 0.4. In some embodiments, the ratio is about 0.5. In some embodiments, the ratio is about 0.6. In some embodiments, the ratio is about 0.7. In some embodiments, the ratio is about 0.8.In some embodiments, the ratio is about 0.9. In some embodiments, the ratio is about 1. In some embodiments, the ratio is about 1.1. In some embodiments, the ratio is about 1.2. In some embodiments, the ratio is about 1.3. In some embodiments, the ratio is about 1.4. In some embodiments, the ratio is about 1.5. In some embodiments, the ratio is about 1.6. In some embodiments, the ratio is about 1.7. In some embodiments, the ratio is about 1.8. In some embodiments, the ratio is about 1.9. In some embodiments, the ratio is about 2. In some embodiments, the ratio is about 2.1. In some embodiments, the ratio is about 2.2. In some embodiments, the ratio is about 2.3. In some embodiments, the ratio is about 2.4. In some embodiments, the ratio is about 2.5. In some embodiments, the ratio is about 1.8 for the composition, and the antibody portion of the plurality of agents is the antibody portion of an IVIG preparation. In some embodiments, the ratio of target binding moieties to antibody moieties is about 1.5 to 2, and the antibody moieties of the plurality of agents are IgG1 antibody moieties. In some embodiments, the ratio of target binding moieties to antibody moieties is about 1.5 to 2, and the antibody moieties of the plurality of agents are IgG2 antibody moieties. In some embodiments, the ratio is about 1.5 to 2, and the antibody moieties of the plurality of agents are IgG4 antibody moieties. In some embodiments, the ratio is about 1.9 to 2.

[0195] In some embodiments, in a provided agent (e.g., an agent of formula MI or M-II, or a salt thereof), substantially all of the conjugation sites on the antibody moieties have the same modification (e.g., all share the same moiety of interest, optionally connected via the same linker moiety). In some embodiments, the conjugation moieties do not have different modifications (e.g., different moieties of interest and / or not the moiety of interest and / or different linker moieties).

[0196] In some embodiments, all or substantially all moieties of interest, e.g., about 10% to 100% of the target-binding moieties, conjugated to the antibody portion or fragment thereof of a particular type of antibody (e.g., IgG1), are conjugated to one or more specific sites, typically one or two specific sites (e.g., K246 and K248 of the IgG1 heavy chain and corresponding amino acid residues). In some embodiments, all or substantially all moieties of interest, e.g., about 10% to 100% of the target-binding moieties, conjugated to the antibody portion or fragment thereof of an IgG2 antibody, are at K251 and K253 and corresponding amino acid residues of the IgG2 heavy chain. In some embodiments, all or substantially all moieties of interest, e.g., about 10% to 100% of the target-binding moieties, conjugated to the antibody portion or fragment thereof of an IgG2 antibody, are at K239 and K241 and corresponding amino acid residues of the IgG4 heavy chain. In some embodiments, about 10% to 100% of all or substantially all of the moieties of interest (e.g., in the case of multiple agents, compositions, etc.) are conjugated to antibody portions of IgG1, IgG2, and / or IgG4 antibodies, or fragments thereof (e.g., in the case of conjugated products with an IgG1 antibody or fragment thereof (wherein the antibody portion is that of an IgG1 antibody or fragment thereof), an IgG2 antibody or fragment thereof (wherein the antibody portion is that of an IgG2 antibody or fragment thereof), an IgG4 antibody or fragment thereof (wherein the antibody portion is that of an IgG4 antibody or fragment thereof), or in the case of conjugated products with IVIG (as described herein). (Selective conjugation with IgG1, IgG2, and IgG4 when certain provided techniques are utilized). In some embodiments, the percentage is about 10% or greater. In some embodiments, the percentage is about 20% or greater. In some embodiments, the percentage is about 25% or greater. In some embodiments, the percentage is about 30% or greater. In some embodiments, the percentage is about 40% or greater. In some embodiments, the percentage is about 50% or greater. In some embodiments, the percentage is about 60% or greater. In some embodiments, the percentage is about 65% or greater.In some embodiments, the percentage is about 70% or greater. In some embodiments, the percentage is about 75% or greater. In some embodiments, the percentage is about 80% or greater. In some embodiments, the percentage is about 85% or greater. In some embodiments, the percentage is about 90% or greater. In some embodiments, the percentage is about 95% or greater. In some embodiments, the percentage is about 100%.

[0197] In some embodiments, a composition comprises a plurality of agents (e.g., MATE agents, agents of formula MI or M-II, or salts thereof), each independently comprising a cell receptor binding moiety, an antibody moiety, and optionally a linker moiety connecting the cell receptor binding moiety and the antibody moiety. In some embodiments, substantially all of the target binding moieties of the plurality of agents are the same. In some embodiments, substantially all of the target binding moieties of the plurality of agents comprise peptide moieties of a common amino acid sequence. In some embodiments, substantially all of the target binding moieties of the plurality of agents are peptide moieties of a common amino acid sequence. In some embodiments, substantially all of the conjugation sites of the antibody moieties in the plurality of agents have the same modification (e.g., all share the same moiety of interest, optionally connected via the same linker moiety). In some embodiments, the conjugation moieties of the plurality of agents do not have different modifications (e.g., different moieties of interest and / or not the moiety of interest and / or different linker moieties). In some embodiments, the plurality of agents does not contain agents that share the same (or substantially the same) antibody moiety but different modifications (e.g., a different moiety of interest and / or not the moiety of interest and / or a different linker moiety). In some embodiments, agents that share the same (or substantially the same) antibody moiety but different modifications (e.g., a different moiety of interest and / or not the moiety of interest and / or a different linker moiety) are intermediates in a multi-step preparation of a final product agent (e.g., including a step for removal of the antibody binding moiety in addition to a step for cell receptor binding moiety conjugation).

[0198] In some embodiments, the present disclosure provides a composition comprising multiple agents, each of which independently: an antibody portion; and a cell receptor binding portion; optionally a linker moiety connecting the antibody moiety and the cell receptor binding moiety; the antibody portions of the plurality of agents comprise a common amino acid sequence, and the plurality of agents independently share a common cell receptor-binding portion at least one common amino acid residue of the common amino acid sequence; A composition is provided in which about 1% to 100% of all agents comprising an antibody portion and a cell receptor binding portion that share a common amino acid sequence are multiple agents.

[0199] In some embodiments, the present disclosure provides a composition comprising multiple agents, each of which independently: an antibody portion; and a cell receptor binding portion; optionally a linker moiety connecting the antibody moiety and the cell receptor binding moiety; the multiple agents share the same or substantially the same antibody portion and cell receptor binding portion at at least one common location; A composition is provided in which about 1% to 100% of all agents comprising an antibody portion and a cell receptor binding portion are multiple agents.

[0200] In some embodiments, the antibody portion is a portion of an IgG1 antibody or fragment thereof. In some embodiments, the antibody portion is a portion of an IgG2 antibody or fragment thereof. In some embodiments, the antibody portion is a portion of an IgG3 antibody or fragment thereof. In some embodiments, the antibody portion is a portion of an IgG4 antibody or fragment thereof. In some embodiments, about 1-100% of all moieties of interest are at a common location. In some embodiments, the cell receptor binding moiety is a cell receptor binding moiety described herein. In some embodiments, the multiple agents are each independently of the formula MI or M-II, or a salt thereof.

[0201] In some embodiments, the antibody portions of the multiple agents comprise a common amino acid sequence. In some embodiments, the antibody portions of the multiple agents comprise a common amino acid sequence in the Fc region. In some embodiments, the antibody portions of the multiple agents comprise a common Fc region. In some embodiments, the antibody portions of the multiple agents can specifically bind to a common antigen. In some embodiments, the antibody portions are monoclonal antibody portions. In some embodiments, the antibody portions are polyclonal antibody portions. In some embodiments, the antibody portions bind to two or more different antigens. In some embodiments, the antibody portions bind to two or more different proteins. In some embodiments, the antibody portions are IVIG portions.

[0202] In some embodiments, the cell receptor binding moieties in the plurality of agents are cell receptor binding moieties. In some embodiments, each cell receptor binding moiety is independently a cell receptor binding moiety. In some embodiments, a composition comprises a plurality of agents, wherein the antibody portions of the plurality of agents comprise a common amino acid sequence, the plurality of agents each share a common cell receptor binding moiety independently linked, optionally via a linker, to a common amino acid residue in the common amino acid sequence, and about 1% to 100% of all agents comprising antibody portions comprising the common amino acid sequence and the common cell receptor binding moiety independently comprise the common cell receptor binding moiety independently linked, optionally via a linker, to the common amino acid residue. In some embodiments, the composition comprises a plurality of agents, wherein the antibody portions of the plurality of agents comprise a common amino acid sequence, and the plurality of agents share a common cell receptor binding moiety that is independently linked, via a common linker, to a common amino acid residue within the common amino acid sequence, and about 1% to 100% of all agents comprising antibody portions that comprise the common amino acid sequence and the common cell receptor binding moiety independently comprise a common cell receptor binding moiety linked, via a common linker, to a common amino acid residue. In some embodiments, the composition comprises a plurality of agents, wherein the antibody portions of the plurality of agents comprise a common amino acid sequence, and the plurality of agents share a common cell receptor binding moiety that is independently linked, optionally via a linker, to a common amino acid residue within the common amino acid sequence, and about 1% to 100% of all agents comprising antibody portions that comprise the common amino acid sequence and the common cell receptor binding moiety are a plurality of agents. In some embodiments, the composition comprises a plurality of agents, wherein the antibody portions of the plurality of agents comprise a common amino acid sequence, the plurality of agents each share a common cell receptor binding moiety that is independently linked via a common linker to a common amino acid residue within the common amino acid sequence, and about 1% to 100% of all agents that comprise an antibody portion that comprises the common amino acid sequence, the common cell receptor binding moiety, and the common linker are a plurality of agents.

[0203] As used in this disclosure, in some embodiments, "at least one" or "one or more" means 1 to 1000, 1 to 500, 1 to 200, 1 to 100, 1 to 90, 1 to 80, 1 to 70, 1 to 60, 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more. In some embodiments, it is 1. In some embodiments, it is 2 or more. In some embodiments, it is about 3. In some embodiments, it is about 4. In some embodiments, it is about 5. In some embodiments, it is about 6. In some embodiments, it is about 7. In some embodiments, it is about 8. In some embodiments, it is about 9. In some embodiments, it is about 10. In some embodiments, it is about 10 or more.

[0204] In some embodiments, the common amino acid sequence is 1 to 1000, 1 to 500, 1 to 400, 1 to 300, 1 to 200, 1 to 100, 1 to 50, 10 to 1000, 10 to 500, 10 to 400, 10 to 300, 10 to 200, 10 to 100, 10 to 50, 20 to 1000, 20 to 500, 20 to 400, 20 to 300, 20 to 200, 20 to 100, 20 to 50, 50 to 1000, The length may be 50-500, 50-400, 50-300, 50-200, 50-100, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 200, 250, 300, 400, 500, 600 or more amino acid residues. In some embodiments, the length is at least 5 amino acid residues. In some embodiments, the length is at least 10 amino acid residues. In some embodiments, the length is at least 50 amino acid residues. In some embodiments, the length is at least 100 amino acid residues. In some embodiments, the length is at least 150 amino acid residues. In some embodiments, the length is at least 200 amino acid residues. In some embodiments, the length is at least 300 amino acid residues. In some embodiments, the length is at least 400 amino acid residues. In some embodiments, the length is at least 500 amino acid residues. In some embodiments, the length is at least 600 amino acid residues.

[0205] In some embodiments, the common amino acid sequence is at least 10%-100%, 50%-100%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the amino acid sequence of the antibody portion, protein drug portion, etc. In some embodiments, it is 10% or more. In some embodiments, it is 20% or more. In some embodiments, it is 30% or more. In some embodiments, it is 40% or more. In some embodiments, it is 50% or more. In some embodiments, it is 60% or more. In some embodiments, it is 70% or more. In some embodiments, it is 80% or more. In some embodiments, it is 90% or more. In some embodiments, it is 100%.

[0206] In some embodiments, one and only one amino acid residue in the common amino acid sequence is linked to a common cell receptor binding moiety, e.g., a common cell receptor binding moiety. In some embodiments, two and only two amino acid residues in the common amino acid sequence are linked to a common cell receptor binding moiety, e.g., a common cell receptor binding moiety. In some embodiments, two or more amino acid residues in the common amino acid sequence are linked to a common cell receptor binding moiety, e.g., a common cell receptor binding moiety. In some embodiments, each common cell receptor binding moiety, e.g., a common cell receptor binding moiety, is independently linked to an amino acid residue in the common amino acid sequence.

[0207] In some embodiments, the common amino acid sequence comprises one or more amino acid residues selected from K246 and K248 and corresponding amino acid residues of an IgG1 heavy chain, K251 and K253 and corresponding amino acid residues of an IgG2 heavy chain, and K239 and K241 and corresponding amino acid residues of an IgG4 heavy chain. In some embodiments, the common amino acid sequence comprises one or more amino acid residues selected from K246 and K248 and corresponding amino acid residues of an IgG1 heavy chain. In some embodiments, the common amino acid sequence comprises one or more amino acid residues selected from K251 and K253 and corresponding amino acid residues of an IgG2 heavy chain. In some embodiments, the common amino acid sequence comprises one or more amino acid residues selected from K239 and K241 and corresponding amino acid residues of an IgG4 heavy chain. In some embodiments, the cell receptor binding moiety is connected to such amino acid residues (optionally via a linker moiety unless explicitly stated). In some embodiments, each cell receptor binding moiety is connected to such amino acid residues, each optionally and independently via a linker moiety.

[0208] In some embodiments, the antibody portions share a high percentage of amino acid sequence homology. In some embodiments, it is between about 50% and 100%. In some embodiments, it is 50%. In some embodiments, it is 60%. In some embodiments, it is 70%. In some embodiments, it is 80%. In some embodiments, it is 90%. In some embodiments, it is 91%. In some embodiments, it is 50%. In some embodiments, it is 92%. In some embodiments, it is 93%. In some embodiments, it is 94%. In some embodiments, it is 95%. In some embodiments, it is 96%. In some embodiments, it is 97%. In some embodiments, it is 98%. In some embodiments, it is 99%. In some embodiments, it is 100%. In some embodiments, it is at least 50%. In some embodiments, it is at least 60%. In some embodiments, it is at least 70%. In some embodiments, it is at least 80%. In some embodiments, it is at least 90%. In some embodiments, it is at least 91%. In some embodiments, it is at least 50%. In some embodiments, it is at least 92%. In some embodiments, it is at least 93%. In some embodiments, it is at least 94%. In some embodiments, it is at least 95%. In some embodiments, it is at least 96%. In some embodiments, it is at least 97%. In some embodiments, it is at least 98%. In some embodiments, it is at least 99%.

[0209] In some embodiments, percentages used herein (e.g., about 1%-100%) are about 10% or greater. In some embodiments, percentages are about 20% or greater. In some embodiments, percentages are about 25% or greater. In some embodiments, percentages are about 30% or greater. In some embodiments, percentages are about 40% or greater. In some embodiments, percentages are about 50% or greater. In some embodiments, percentages are about 60% or greater. In some embodiments, percentages are about 65% or greater. In some embodiments, percentages are about 70% or greater. In some embodiments, percentages are about 75% or greater. In some embodiments, percentages are about 80% or greater. In some embodiments, percentages are about 85% or greater. In some embodiments, percentages are about 90% or greater. In some embodiments, percentages are about 95% or greater. In some embodiments, the percentage is about 100%.

[0210] In some embodiments, the antibody portions of the agents comprise a common Fc region or fragment thereof.

[0211] In some embodiments, the moieties of interest of the multiple agents are at specific positions. In some embodiments, all of the moieties of interest are at amino acid residues of a common amino acid sequence. In some embodiments, all of the moieties of interest are at common positions of amino acid residues of a common amino acid sequence. In some embodiments, the number of common positions is 1. In some embodiments, it is 2. In some embodiments, it is 3. In some embodiments, it is 4. In some embodiments, the antibody moiety comprises two heavy chains or fragments thereof, and the number of common positions is 2 (one on each chain). In some embodiments, the common positions are selected from K246 and K248 and corresponding amino acid residues of an IgG1 heavy chain, K251 and K253 and corresponding amino acid residues of an IgG2 heavy chain, and K239 and K241 and corresponding amino acid residues of an IgG4 heavy chain.

[0212] In some embodiments, the multiple agents independently share a common cell receptor binding moiety at at least one position. In some embodiments, the multiple agents independently share a common cell receptor binding moiety and linker at at least one position. In some embodiments, the moieties of interest at two or more or all positions comprise a common cell receptor binding moiety. In some embodiments, the moieties of interest are the same.

[0213] In some embodiments, the agents share a common modification at at least one common amino acid residue. In some embodiments, multiple agents share a common modification at each position connected to the cell receptor binding moiety and, optionally, the linker. In some embodiments, multiple agents share the same -L at each position connected to the linker moiety. PM -TBT.

[0214] In some embodiments, the position is selected from K246, K248, K288, K290, K317, and positions corresponding thereto, of an antibody agent. In some embodiments, the position is selected from K246 and K248, and positions corresponding thereto. In some embodiments, the position is selected from K288 and K290, and positions corresponding thereto. In some embodiments, the position is K246, or a position corresponding thereto. In some embodiments, the position is K248, or a position corresponding thereto. In some embodiments, the position is K288, or a position corresponding thereto. In some embodiments, the position is K290, or a position corresponding thereto. In some embodiments, the position is K317, or a position corresponding thereto. In some embodiments, the position is K185 of the light chain, or a position corresponding thereto. In some embodiments, the position is K187 of the light chain, or a position corresponding thereto. In some embodiments, the position is K133 of the heavy chain, or a position corresponding thereto. In some embodiments, the position is K246 or K248 of the heavy chain, or a position corresponding thereto. In some embodiments, the position is K414 of the heavy chain, or a position corresponding thereto. In some embodiments, the consensus sequence is about or at least about 10-100, 20-50, e.g., about or at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 amino acid residues in length and includes one or more of such residues or their corresponding residues. In some embodiments, the consensus sequence is a sequence that is about or at least about 10 to 100, 20 to 50, for example, about or at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 amino acid residues in length, and includes one or more residues selected from K246 and K248 of the IgG1 heavy chain and their corresponding amino acid residues, K251 and K253 of the IgG2 heavy chain and their corresponding amino acid residues, and K239 and K241 of the IgG4 heavy chain and their corresponding amino acid residues.

[0215] In some embodiments, between about 1% and 100% of all drugs comprising an antibody portion and a cell receptor binding portion are multiple drugs. In some embodiments, between about 1% and 100% of all drugs comprising an antibody portion and a cell receptor binding portion that comprise a common amino acid sequence are multiple drugs. In some embodiments, between about 1% and 100% of all drugs comprising an antibody portion and a cell receptor binding portion that comprise a common amino acid sequence or that can bind to a common antigen are multiple drugs. In some embodiments, between about 1% and 100% of all drugs comprising an antibody portion are multiple drugs. In some embodiments, between about 1% and 100% of all drugs comprising an antibody portion that comprise a common amino acid sequence are multiple drugs. In some embodiments, between about 1% and 100% of all drugs comprising a protein drug portion that comprise a common amino acid sequence are multiple drugs. In some embodiments, between about 1% and 100% of all drugs comprising an antibody drug portion that comprise a common amino acid sequence or that can bind to a common antigen are multiple drugs. In some embodiments, the percentage is between about 5% and 100%. In some embodiments, the percentage is about 10% to 100%. In some embodiments, the percentage is about 20% to 100%. In some embodiments, the percentage is about 25% to 100%. In some embodiments, the percentage is about 30% to 100%. In some embodiments, the percentage is about 40% to 100%. In some embodiments, the percentage is about 50% to 100%. In some embodiments, it is about 5%. In some embodiments, it is about 10%. In some embodiments, it is about 20%. In some embodiments, it is about 25%. In some embodiments, it is about 30%. In some embodiments, it is about 40%. In some embodiments, it is about 50%. In some embodiments, it is about 60%. In some embodiments, it is about 70%. In some embodiments, it is about 80%. In some embodiments, it is about 90%. In some embodiments, it is about 91%. In some embodiments, it is about 50%. In some embodiments, it is about 92%. In some embodiments, it is about 93%. In some embodiments, it is about 94%.In some embodiments, it is about 95%. In some embodiments, it is about 96%. In some embodiments, it is about 97%. In some embodiments, it is about 98%. In some embodiments, it is about 99%. In some embodiments, it is about 100%. In some embodiments, it is at least about 5%. In some embodiments, it is at least about 10%. In some embodiments, it is at least about 20%. In some embodiments, it is at least about 25%. In some embodiments, it is at least about 30%. In some embodiments, it is at least about 40%. In some embodiments, it is at least about 50%. In some embodiments, it is at least about 60%. In some embodiments, it is at least about 70%. In some embodiments, it is at least about 80%. In some embodiments, it is at least about 90%. In some embodiments, it is at least about 91%. In some embodiments, it is at least about 50%. In some embodiments, it is at least about 92%. In some embodiments, it is at least about 93%. In some embodiments, it is at least about 94%. In some embodiments, it is at least about 95%. In some embodiments, it is at least about 96%. In some embodiments, it is at least about 97%. In some embodiments, it is at least about 98%. In some embodiments, it is at least about 99%.

[0216] In some embodiments, each of the plurality of agents does not contain -S-Cy-, where -Cy- is an optionally substituted 5-membered monocyclic ring, does not contain -SS- that is not formed by a cysteine ​​residue, and does not contain -SH or a salt form thereof that is not of a cysteine ​​residue. In some embodiments, each of the plurality of agents does not contain -S-CH2-CH2-. In some embodiments, each of the plurality of agents does not contain a moiety that can specifically bind to an antibody drug. In some embodiments, the composition is substantially free of a moiety that can specifically bind to an antibody drug.

[0217] In some embodiments, the provided agents, compounds, etc. (e.g., those of formula RI, MI, M-II, etc.) and salts thereof have a high degree of purity. In some embodiments, the percentage is about 5% to 100%. In some embodiments, the percentage is about 10% to 100%. In some embodiments, the percentage is about 20% to 100%. In some embodiments, the percentage is about 25% to 100%. In some embodiments, the percentage is about 30% to 100%. In some embodiments, the percentage is about 40% to 100%. In some embodiments, the percentage is about 50% to 100%. In some embodiments, it is about 5%. In some embodiments, it is about 10%. In some embodiments, it is about 20%. In some embodiments, it is about 25%. In some embodiments, it is about 30%. In some embodiments, it is about 40%. In some embodiments, it is about 50%. In some embodiments, it is about 60%. In some embodiments, it is about 70%. In some embodiments, it is about 80%. In some embodiments, it is about 90%. In some embodiments, it is about 91%. In some embodiments, it is about 50%. In some embodiments, it is about 92%. In some embodiments, it is about 93%. In some embodiments, it is about 94%. In some embodiments, it is about 95%. In some embodiments, it is about 96%. In some embodiments, it is about 97%. In some embodiments, it is about 98%. In some embodiments, it is about 99%. In some embodiments, it is about 100%. In some embodiments, it is at least about 5%. In some embodiments, it is at least about 10%. In some embodiments, it is at least about 20%. In some embodiments, it is at least about 25%. In some embodiments, it is at least about 30%. In some embodiments, it is at least about 40%. In some embodiments, it is at least about 50%. In some embodiments, it is at least about 60%. In some embodiments, it is at least about 70%.In some embodiments, it is at least about 80%. In some embodiments, it is at least about 90%. In some embodiments, it is at least about 91%. In some embodiments, it is at least about 50%. In some embodiments, it is at least about 92%. In some embodiments, it is at least about 93%. In some embodiments, it is at least about 94%. In some embodiments, it is at least about 95%. In some embodiments, it is at least about 96%. In some embodiments, it is at least about 97%. In some embodiments, it is at least about 98%. In some embodiments, it is at least about 99%.

[0218] In some embodiments, the disclosure provides a product drug composition comprising a product drug (e.g., an agent of formula MI or M-II, or a salt thereof). In some embodiments, the product drug composition (e.g., a drug composition formed from a particular method) comprises an antibody portion and a cell receptor binding portion, and optionally a linker (e.g., an agent of formula MI or M-II, or a salt thereof), a released antibody binding portion (e.g., R LG -(L LG1 ) 0~1 -(L LG2 ) 0~1 -(L LG3 ) 0~1 -(L LG4 ) 0~1 -)) or a compound containing a released antibody binding moiety (e.g., R LG -(L LG1 ) 0~1 -(L LG2 ) 0~1 -(L LG3 ) 0~1 -(L LG4 ) 0~1The product drug includes a compound having the structure -H, or a salt thereof, and a reactive partner (e.g., a compound of formula RI, or a salt thereof). In some embodiments, the released antibody-binding moiety may bind to the targeting drug and / or the antibody moiety in the formed product drug. For example, in accordance with the present disclosure, in some embodiments, a composition is contacted with a composition comprising glycine at a particular pH. Various techniques are available for separating the released antibody-binding moiety from the antibody moiety. In some embodiments, each of the multiple drugs is independently such a product drug.

[0219] reactive groups In some embodiments, provided agents, compounds (e.g., those useful as reaction partners, such as first agents) comprise a reactive group (e.g., RG). In some embodiments, the reactive group (e.g., RG) is located between the antibody binding moiety (e.g., ABT) and the moiety of interest (e.g., MOI), and is optionally and independently linked to the antibody binding moiety and the moiety of interest via a linker. In some embodiments, RG is a reactive group described herein.

[0220] In some embodiments, reactive groups, when utilized in agents that do not include an antibody binding moiety, react slowly, resulting in low levels of conjugation of the moiety of interest with the targeted agent, and in some embodiments, substantially no conjugation of the moiety of interest with the targeted agent. As demonstrated herein, the combination of a reactive group and an antibody binding moiety in the same agent, such as, for example, a compound of Formula RI or a salt thereof, can, among other things, facilitate the reaction between the reactive group and the targeted agent, enhance reaction efficiency, reduce side reactions, and / or improve reaction selectivity (e.g., with respect to the target site at which conjugation of the moiety of interest with the targeted agent occurs).

[0221] The reactive group in the drug can react with various types of groups in the targeting drug. In some embodiments, the reactive group in the drug selectively reacts with an amino group of the targeting drug, e.g., an —NH2 group on the side chain of a lysine residue in a protein. In some embodiments, when utilized in a drug (e.g., one of formula RI or a salt thereof), the reactive group selectively reacts with a specific site of the targeting drug, e.g., one or more of K246, K248, K288, K290, K317, etc. of IgG1, K251, K253, etc. of IgG2, and K239 and K241 of IgG4, as shown in the examples herein. In some embodiments, the site is K246 or K248 of the antibody heavy chain. In some embodiments, the site is K246 and / or K248 of the antibody heavy chain. In some embodiments, the site is K246 of the antibody heavy chain. In some embodiments, the site is K248 of the antibody heavy chain. In some embodiments, the site is K288 or K290 of the antibody heavy chain. In some embodiments, the site is K288 of the antibody heavy chain. In some embodiments, the site is K290 of the antibody heavy chain. In some embodiments, the site is K317. In some embodiments, the site is K414 of the antibody heavy chain. In some embodiments, the site is K185 of the antibody light chain. In some embodiments, the site is K187 of the antibody light chain. In some embodiments, the site is K251 and / or K253 of an IgG2 heavy chain. In some embodiments, the site is K251 of an IgG2 heavy chain. In some embodiments, the site is K253 of an IgG2 heavy chain. In some embodiments, the site is K239 and / or K241 of an IgG4 heavy chain. In some embodiments, the site is K239 of an IgG4 heavy chain. In some embodiments, the site is K241 of an IgG4 heavy chain. In some embodiments, conjugation occurs preferentially at one or more heavy chain sites over light chain sites, hi some embodiments, for technologies that do not have antibody binding moieties, conjugation occurs at light chain sites over heavy chain sites.

[0222] In some embodiments, the reactive group (e.g., RG) is or includes an ester group. In some embodiments, the reactive group (e.g., RG) is or includes an electrophilic group (e.g., a Michael acceptor).

[0223] In some embodiments, the reactive group (e.g., RG) is -L RG1 -L RG2 - or contains L RG1 and L RG2 and each independently is L, as described herein. In some embodiments, the reactive group (e.g., RG) is -L LG4 -L RG1 -L RG2 In some embodiments, the reactive group (e.g., RG) is or includes -L LG3 -L LG4 -L RG1 -L RG2 In some embodiments, the reactive group (e.g., RG) is or includes -L LG2 -L LG3 -L LG4 -L RG1 -L RG2 In some embodiments, the reactive group (e.g., RG) is or includes -L LG4 -L RG2 In some embodiments, the reactive group (e.g., RG) is or includes -L LG3 -L LG4 -L RG2 In some embodiments, the reactive group (e.g., RG) is or includes -L LG2 -L LG3 -L LG4 -L RG2 -, where each variable is as described herein.

[0224] In some embodiments, LLG4 is —O—. In some embodiments, L LG4 is -N(R)-. In some embodiments, L LG4 is -NH-.

[0225] In some embodiments, L LG3 is or includes an optionally substituted aryl ring. In some embodiments, L LG3 is or includes a phenyl ring. In some embodiments, the aryl or phenyl ring is substituted. In some embodiments, the substituent is an electron-withdrawing group as described herein, such as -NO, -F, etc.

[0226] In some embodiments, L RG1 is a covalent bond. In some embodiments, L RG1 is not a covalent bond. RG1 is -S(O)2-.

[0227] In some embodiments, L RG2 is —C(O)—. In some embodiments, the reactive group is —L LG4 In some embodiments, the reactive group is or includes -C(O)-, where each variable is as described herein. LG3 -L LG4 In some embodiments, the reactive group is or includes -C(O)-, where each variable is as described herein. LG2 -L LG3 -L LG4 is or includes -C(O)-, where each variable is as described herein.

[0228] In some embodiments, L RG2 -L RG3 -C(=CR RG1 R RG2 )-CR RG3 R RG4 - and R RG1 , R RG2 , R RG3 and RRG4 each independently is -L-R', and L RG3 is —C(O)—, —C(O)O—, —C(O)N(R′)—, —S(O)—, —S(O)—, —P(O)(OR′)—, —P(O)(SR′)—, or —P(O)(N(R′))—. In some embodiments, R RG1 , R RG2 , R RG3 and R RG4 Each of is independently R'. In some embodiments, R RG1 , R RG2 , R RG3 and R RG4 and one or more of L are independently -H. RG3 is —C(O)—. In some embodiments, L RG3 is —C(O)O—. In some embodiments, L RG3 -O-, -N(R')-, etc. are L PM is connected to

[0229] In some embodiments, R RG1 is —H. In some embodiments, R RG3 is -H.

[0230] In some embodiments, L RG2 is optionally substituted -L RG3 -C(=CHR RG2 )-CHR RG4 - where each variable is as described herein.

[0231] In some embodiments, R RG2 and R RG4are taken together with their intervening atoms to form an optionally substituted ring as described herein. In some embodiments, the ring formed is an optionally substituted 3-10 membered monocyclic or bicyclic ring having 0-5 heteroatoms. In some embodiments, the ring formed is an optionally substituted 3-10 membered alicyclic ring. In some embodiments, the ring formed is an optionally substituted 3-8 membered alicyclic ring. In some embodiments, the ring formed is an optionally substituted 5-8 membered alicyclic ring. In some embodiments, the ring formed is an optionally substituted 5-membered alicyclic ring. In some embodiments, the ring formed is an optionally substituted 6-membered alicyclic ring. In some embodiments, the ring formed is an optionally substituted 7-membered alicyclic ring. In some embodiments, the ring formed is substituted. In some embodiments, the ring formed is unsubstituted. In some embodiments, the ring formed is C(=CHR RG2 ) or C(=CR RG1 R RG2 ) does not contain additional unsaturation in addition to the double bond in

[0232] In some embodiments, —C(═CHR RG2 )-CHR RG4 or -C(=CR RG1 R RG2 )-CR RG3 R RG4 is optionally substituted [ka] In some embodiments, -C(=CHR RG2 )-CHR RG4 or -C(=CR RG1 R RG2 )-CR RG3 R RG4 teeth, [ka] In some embodiments, -[C(=CHR RG2 )-CHR RG4 ]-LRG3 -or-[C(=CR RG1 R RG2 )-CR RG3 R RG4 ]-L RG3 - is optionally substituted [ka] In some embodiments, -[C(=CHR RG2 )-CHR RG4 ]-L RG3 -or-[C(=CR RG1 R RG2 )-CR RG3 R RG4 ]-L RG3 -teeth, [ka] In some embodiments, -L RG1 -[C(=CHR RG2 )-CHR RG4 ]-L RG3 -or-L RG1 -[C(=CR RG1 R RG2 )-CR RG3 R RG4 ]-L RG3 - is optionally substituted [ka] In some embodiments, -L RG1 -[C(=CHR RG2 )-CHR RG4 ]-L RG3 -or-L RG1 -[C(=CR RG1 R RG2 )-CR RG3 R RG4 ]-L RG3 - is optionally substituted [ka] is.

[0233] In some embodiments, the reactive group is a structure selected from the following table: LG2 -L LG3 -L LG4 -L RG1 -L RG2 - is a structure selected from the table below. LG2 -L LG3 -L LG4 -L RG1 - is a structure selected from the table below. Table RG-1. Specific structures as examples. [ka] [ka] .

[0234] In some embodiments, -L LG4 -L RG2 - is -OC(O)-. In some embodiments, -L LG4 -L RG2 - is -SC(O)-. In some embodiments, -L LG4 -L RG1 -L RG2 - is -SC(O)-.

[0235] In some embodiments, -L LG4 -L RG2 - is -N(-)-C(O)-, where N is a ring atom of an optionally substituted heteroaryl ring. LG4 -L RG2 - is -N(-)-C(O)-, where N is or contains an optionally substituted heteroaryl ring; LG4 In some embodiments, -L LG4 -L RG2 - is -N(-)-C(O)-O-, where N is or contains an optionally substituted heteroaryl ring. LG4 is a ring atom of

[0236] In some embodiments, L RG2 is an optionally substituted —CH—C(O)—, where —CH— is bonded to an electron-withdrawing group that comprises or is attached to an antibody binding moiety. RG2 is an optionally substituted —CH— bonded to an electron withdrawing group comprising or attached to an antibody binding moiety. RG1 is an electron withdrawing group. RG1 is —C(O)—. In some embodiments, L RG1 is —S(O)—. In some embodiments, L RG1 is -S(O)-. In some embodiments, L RG1 is -P(O(OR)-. In some embodiments, L RG1 is —P(O(SR)—. In some embodiments, L RG1 is -P(O(N(R)2)-. In some embodiments, L RG1 is -OP(O(OR)-. In some embodiments, L RG1 is -OP(O(SR)-. In some embodiments, L RG1 is -OP(O(N(R)2)-.

[0237] In some embodiments, L RG2 is an optionally substituted —CH—C(O)—, where —CH— is attached to a leaving group that comprises or is attached to an antibody binding moiety. RG2 is an optionally substituted —CH— that comprises an antibody binding moiety or is attached to a leaving group attached thereto. RG1 is -OC(O)-. In some embodiments, L RG1 is —OS(O)—. In some embodiments, L RG1 is -OP(O(OR)-. In some embodiments, L RG1 is -OP(O(SR)-. In some embodiments, L RG1 is -OP(O(N(R)2)-.

[0238] In some embodiments, the reactive group reacts with an amino group of the targeting agent, hi some embodiments, the amino group is -NH2 of the side chain of a lysine residue.

[0239] In some embodiments, the targeting agent is a protein drug. In some embodiments, the targeting agent is an antibody drug. In some embodiments, the reactive group reacts with an amino acid residue of such a protein or antibody drug. In some embodiments, the amino acid residue is a lysine residue. In some embodiments, the reactive group reacts with -NH2 of the side chain of the lysine residue. In some embodiments, the reactive group is or includes -C(O)-O-, which reacts with -NH2 (e.g., of the side chain of the lysine residue) to form an amide group, -C(O)-O-, with -NH2.

[0240] In some embodiments, the reactive groups (e.g., first reactive group, second reactive group, etc.) are located at terminal positions. In some embodiments, an agent, such as a first agent, comprises a first reactive group optionally linked to a target binding moiety via a linker moiety and does not comprise an antibody binding moiety.

[0241] In some embodiments, the disclosure provides a method for preparing a composition comprising multiple agents, wherein each agent independently comprises: an antibody portion; and a cell receptor binding portion; optionally a linker moiety connecting the antibody moiety and the cell receptor binding moiety; The method is A method is provided that includes contacting a plurality of agents, each of which independently comprises a reactive group, with a plurality of antibody agents.

[0242] In some embodiments, the reactive group-containing agent comprises an antibody binding moiety, a cell receptor binding moiety, and optionally a linker. In some embodiments, the reactive group-containing agents share the same cell receptor binding moiety. In some embodiments, the reactive group-containing agents share the same structure. In some embodiments, the antibody molecules have structures, properties, and / or activities that provide the antibody moiety in the agent described herein. In some embodiments, the plurality of antibody molecules comprises two or more IgG subclasses. In some embodiments, the plurality of antibody molecules comprises IgG1. In some embodiments, the plurality of antibody molecules comprises IgG2. In some embodiments, the plurality of antibody molecules comprises IgG4. In some embodiments, the plurality of antibody molecules comprises IgG1 and IgG2. In some embodiments, the plurality of antibody molecules comprises IgG1, IgG2, and IgG4. In some embodiments, the plurality of antibody molecules comprises IgG1, IgG2, IgG3, and IgG4. In some embodiments, the plurality of antibody molecules are IVIG antibody molecules.

[0243] In some embodiments, provided agents include a reactive group, e.g., [ka] In some embodiments, -C(O)- is connected, optionally via a linker, to a cell receptor binding moiety or a moiety comprising -(Xaa)y-, and the other end is connected to an antibody binding moiety. [ka] reacts with an amino group of another moiety, e.g., an antibody moiety, to form an amide group with that moiety, releasing a moiety that is or includes an antibody-binding moiety. In some embodiments, the amino group is -NH2 of a lysine side chain. In some embodiments, -C(O)- is connected, optionally via a linker, to a cell receptor-binding moiety or a moiety that includes -(Xaa)y-, and the other end is connected to R' or an optional substituent. In some embodiments, provided agents are optionally substituted [ka] Such reactive groups may be useful for conjugation with detection, diagnostic, or therapeutic agents. Those skilled in the art will appreciate that a variety of agents and numerous techniques (e.g., click chemistry, reactions based on functional groups such as amino groups (e.g., amide formation), hydroxyl groups, carboxyl groups, etc.) can be utilized for conjugation according to the present disclosure.

[0244] In some embodiments, the antibody binding moiety binds to the Fc region of an antibody. In some embodiments, the reaction occurs with a residue in the Fc region. In some embodiments, the target binding moiety is conjugated to a residue in the Fc region, optionally via a linker moiety. In some embodiments, the residue is a Lys residue. In some embodiments, the antibody is or comprises an IgG1. In some embodiments, the antibody is or comprises an IgG2. In some embodiments, the antibody is or comprises an IgG4. In some embodiments, the antibody composition utilized in the method comprises IgG1 and IgG2. In some embodiments, the antibody composition utilized in the method comprises IgG1, IgG2, and IgG4. In some embodiments, the antibody composition utilized in the method comprises IgG1, IgG2, IgG3, and IgG4.

[0245] In some embodiments, the product is or comprises IgG1. In some embodiments, the product is or comprises IgG2. In some embodiments, the product is or comprises IgG4. In some embodiments, the product composition comprises IgG1 and IgG2. In some embodiments, the product composition comprises IgG1, IgG2, and IgG4. In some embodiments, the product composition comprises IgG1, IgG2, IgG3, and IgG4.

[0246] In some embodiments, provided agents comprising an antibody portion provide one or more or substantially all of the antibody's immune activities, e.g., to recruit one or more types of immune cells, and / or provide short-term and long-term immune activity. In some embodiments, provided agents comprising an antibody portion do not significantly reduce one or more or substantially all of the relevant antibody immune activities. In some embodiments, provided agents comprising an antibody portion improve one or more or substantially all of the relevant antibody immune activities (e.g., compared to the antibody portion itself). In some embodiments, provided agents provide equivalent or better stability (e.g., residence time in blood) compared to the antibody portion itself. In some embodiments, the antibody portion in a provided agent can bind to the FcRy of immune cells (e.g., various FcRy of immune effector cells for the desired immune activity, typically at equivalent or better levels). In some embodiments, the antibody portion in a provided agent has equivalent Fab / antigen binding ability. In some embodiments, the antibody portion in a provided agent has equivalent Fab / antigen binding ability. In some embodiments, the antibody portion in a provided agent provides FcRn binding. In some embodiments, the antibody moiety in the provided agents provides FcRn binding, e.g., for antibody recycling and / or extended half-life. In some embodiments, the provided technology is particularly useful for modifying blood-derived IgG products, as the provided technology is suitable for and can be utilized with all IgG subclasses.

[0247] In some embodiments, the provided method includes one of the steps described below. [ka] reacts with the amino group of the lysine side chain to form an amide bond with the antibody molecule, [ka] or a salt form thereof.

[0248] Linker part In some embodiments, the moieties are optionally connected to one another via a linker moiety. For example, in some embodiments, the reactive group (e.g., RG) is linked to a linker (e.g., L RM In some embodiments, the moiety (e.g., LG) is also connected to the cell receptor binding moiety (e.g., TBT) via one or more linkers, e.g., L, for linking to various moieties. LG1 , L LG2 , L LG3 , L LG4 In some embodiments, L LG is a linker moiety as described herein. In some embodiments, L LG1 is a linker moiety as described herein. In some embodiments, L LG2 is a linker moiety as described herein. In some embodiments, L LG3 is a linker moiety as described herein. In some embodiments, L LG4 is a linker moiety as described herein. In some embodiments, L RM is a linker moiety as described herein. In some embodiments, L PM is L as described herein. In some embodiments, L PM is a linker moiety as described herein. In some embodiments, L PM is L as described herein.

[0249] Linker moieties of various types and / or for various purposes (such as those utilized in antibody-drug conjugates) may be utilized in accordance with the present disclosure.

[0250] Linker moieties can be either bivalent or multivalent depending on how they are used. In some embodiments, the linker moiety is bivalent. In some embodiments, the linker is multivalent and connects more than two moieties.

[0251] In some embodiments, the linker moiety, e.g., L z (wherein z represents a superscript, e.g., L PM , LRM , L LG , L LG1 etc.) is or contains L.

[0252] In some embodiments, L is a covalent bond or a divalent or polyvalent optionally substituted straight or branched C alkyl group comprising one or more aliphatic, aryl, heteroaliphatic having 1 to 20 heteroatoms, heteroaromatic having 1 to 20 heteroatoms, or any combination thereof. 1~100 is a group, wherein one or more methylene units of the group are optionally and independently selected from C 1~6 Alkylene, C 1~6 Alkenylene, divalent C with 1 to 5 heteroatoms 1~6 Heteroaliphatic group, -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')- , -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- , -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P( S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n ]- (wherein n is 1 to 20). The linker optionally contains a cyclic group (Cy), defined below, and a reactive group (RG), defined below. In some embodiments, each amino acid residue is independently a residue of an amino acid having the structure of formula AI, or a salt thereof. In some embodiments, each amino acid residue is independently replaced with -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 It has the structure —CO— or a salt thereof.

[0253] In some embodiments, L is divalent. In some embodiments, L is a covalent bond.

[0254] In some embodiments, L is C 1~00 Aliphatic and C with 1-50 heteroatoms 1~100 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently selected from C 1~6 Alkylene, C 1~6 Alkenylene, divalent C with 1 to 5 heteroatoms 1~6 Heteroaliphatic group, -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')- , -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- , -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P( S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is replaced by C. 1~20 Aliphatic and C with 1-10 heteroatoms 1~20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently selected from C 1~6 Alkylene, C 1~6 Alkenylene, divalent C with 1 to 5 heteroatoms 1~6Heteroaliphatic group, -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')- , -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- , -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P( S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is replaced with C. 1~20 a divalent or optionally substituted straight or branched group selected from aliphatic, wherein one or more methylene units of the group are optionally and independently selected from -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)- , -S(O)2-, -S(O)2N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, - P(S)(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is a divalent or optionally substituted straight or branched C 1~20is aliphatic, wherein one or more methylene units of the group are optionally and independently -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, -C(O)O-, an amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~100 is aliphatic, and one or more methylene units of the group are optionally and independently -C≡C-, -Cy-, -C(R')2-, -O-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, an amino acid residue, or -[(-OC(R')2-C(R')2-) n In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~50 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~40 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~20 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~10In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~100 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~50 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~40 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~20 In some embodiments, L is a divalent or optionally substituted linear or branched group C 1~10 alkylene, wherein one or more methylene units of the group are optionally and independently replaced as described herein.

[0255] In some embodiments, a linker moiety (e.g., L, L PM , L RM etc.) contain an acidic group, e.g., —S(O)2OH.

[0256] In some embodiments, L is -[(-OC(R')2-C(R')2-) n In some embodiments, L is or includes -[(-O-CH-CH-) n]-. In some embodiments, L is or comprises -[(-CH2-CH2-O)6]-CH2-CH2-. In some embodiments, L is -[(-CH2-CH2-O)8]-CH2-CH2-. In some embodiments, -CH2-CH2-O- is attached to the antibody binding moiety at -CH2-. In some embodiments, -CH2-CH2-O- is attached to the cell receptor binding moiety at -CH2-. In some embodiments, L PM is L as described herein. In some embodiments, L RM is L as described herein.

[0257] In some embodiments, a linker moiety (e.g., L) is or includes one or more -(CH2)nO-, where each n is independently 1 to 20. In some embodiments, it is or includes one or more -[(CH2)nO]m-, where each n is independently 1 to 20 and m is 1 to 100. In some embodiments, it includes two or more -[(CH2)nO]m-, where each n is independently 1 to 20 and m is 1 to 100. In some embodiments, it is or includes one or more of -(O)C-[(CH2)nO]m(CH2)nNH-, -[(CH2)nO]mNHC(O)[(CH2)nO]mNH-, -[(CH2)nO]m{NHC(O)[(CH2)nO]m}pNH--, where each n is independently 1 to 20, each m is independently 1 to 100, and each p is independently 1 to 10. In some embodiments, n is 1 to 10. In some embodiments, n is 1 to 5. In some embodiments, each n is 2. In some embodiments, m is 1 to 50. In some embodiments, m is 1 to 40. In some embodiments, m is 1 to 30. In some embodiments, m is 1 to 20. In some embodiments, m is 1 to 10. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 7. In some embodiments, m is 8. In some embodiments, m is 9. In some embodiments, m is 10. In some embodiments, m is 11. In some embodiments, m is 12. In some embodiments, m is 13. In some embodiments, m is 14. In some embodiments, m is 15. In some embodiments, m is 16. In some embodiments, m is 17. In some embodiments, m is 18. In some embodiments, m is 19. In some embodiments, m is 20.

[0258] In some embodiments, the linker moiety, or L, is or includes -(CH2CHO)n-, where each -CH2- is independently and optionally substituted, and n is 1 to 20. In some embodiments, the linker moiety, or L, is or includes -(CH2)nO-(CH2CHO)n-(CH2)n-, where each n is independently 1 to 10, and each -CH2- is independently and optionally substituted.

[0259] In some embodiments, the linker moiety is trivalent or multivalent. For example, in some embodiments, the linker moiety is L, as described herein, and L is trivalent or multivalent. In some embodiments, L is trivalent. For example, in some embodiments, L is -CH2-N(-CH2-)-C(O)-.

[0260] In some embodiments, the linker moiety (eg, L) comprises one or more amino acid residues or analogs thereof.

[0261] In some embodiments, a linker moiety (e.g., L, L RM (e.g., -O- ... [ka] wherein Rs is halogen, -NO2, -F, -L-R', -C(O)-L-R', -S(O)-L-R', -S(O)2-L-R', or -P(O)(-L-R')2. In some embodiments, an aryl group is [ka] wherein each R s are independently halogen, -NO2, -F, -L-R', -C(O)-L-R', -S(O)-L-R', -S(O)2-L-R', or -P(O)(-L-R')2. In some embodiments, an aryl group is [ka] In some embodiments, the aryl group is [ka] In some embodiments, C1 is linked to the -O- of -C(O)-O-. In some embodiments, the cell receptor binding moiety is on the -C(O)- side and the antibody binding moiety is on the -O- side.

[0262] In some embodiments, a linker moiety (e.g., L, L RM In some embodiments, the reactive group is: [ka] wherein -C(O)- is connected, optionally via a linker, to the cell receptor binding moiety or the moiety comprising -(Xaa)y-. In some embodiments, the reactive group is [ka] wherein -C(O)- is connected, optionally via a linker, to a cell receptor binding moiety or a moiety comprising -(Xaa)y-, and the other end of the reactive group is connected to an antibody binding moiety.

[0263] In some embodiments, L is or includes a product moiety of a bioorthogonal or enzymatic reaction. In some embodiments, L is or includes an optionally substituted triazole moiety (which is optionally part of a bicyclic or polycyclic ring system). In some embodiments, L is or includes LPXTG. In some embodiments, L is or includes LPETG. In some embodiments, L is or includes LPXT(G)n, where n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, L is or includes LPET(G)n, where n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0264] In some embodiments, a linker moiety (e.g., L, L RM In some embodiments, the linker moiety (e.g., L, L, etc.) does not contain a reactive group. RM In some embodiments, the linker moiety (e.g., L, L) does not contain a reactive group that readily reacts with proteins under aqueous conditions at a pH of about 6-9 (e.g., physiological conditions). RM etc.) do not contain reactive groups that readily react with natural amino acid residues under aqueous conditions of about pH 6-9 (e.g., physiological conditions).

[0265] In some embodiments, a linker moiety (e.g., L, L RM etc.) does not contain -S- and neither of the two atoms to which -S- is attached is S. In some embodiments, a linker moiety (e.g., L, L RM In some embodiments, a linker moiety (e.g., L, L, etc.) does not contain -SS-. RMIn some embodiments, a linker moiety (e.g., L, L, etc.) does not contain an -S- attached to the beta carbon of the carbonyl group or a double or triple bond conjugated to the carbonyl group. RM etc.) are [ka] In some embodiments, the linker moiety (e.g., L, L RM etc.) do not contain -S-.

[0266] In some embodiments, the agent comprises a linker that is not a covalent bond. In some embodiments, the linker is about 1-200, 1-150, 1-100, 1-90, 1-80, 1-70, 1-60, 1-50, 1-40, 1-30, 10-200, 10-150, 10-100, 10-90, 10-80, 10-70, 10-60, 10-50, 10-40, 10-30, 20-200, 20-150, 20-100, 20-90, 20-80, 20-70, 20 and has a length (shortest path between connected moieties) of up to 60, 20 to 50, 20 to 40, 20 to 30, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 atoms or bonds.

[0267] In some embodiments, the provided compounds / agents (e.g., reaction partners, agents (e.g., products of the provided methods and / or steps therein) do not comprise a cleavable group (other than one or more reactive groups and / or moieties therein) that can be cleaved under conditions that do not substantially damage or transform the targeting agent and / or agent comprising a targeting agent moiety (e.g., a conjugation product comprising a targeting agent moiety). In some embodiments, the provided compounds / agents (e.g., reaction partners, agents (e.g., products of the provided methods and / or steps therein) do not comprise a cleavable group (other than one or more reactive groups and / or moieties therein) that can be cleaved under conditions that do not substantially damage or transform the targeting agent and / or agent comprising a targeting agent moiety (e.g., a conjugation product comprising a targeting agent moiety) for one or more uses (e.g., use as a diagnostic agent, a therapeutic agent, etc.). In some embodiments, the provided compounds / agents (e.g., reaction partners, agents (e.g., products of the provided methods and / or steps therein) do not comprise a cleavable group (other than one or more reactive groups and / or moieties therein) that can be cleaved under bioorthogonal conditions. In some embodiments, provided compounds / agents (e.g., reaction partners, agents (e.g., products of provided methods and / or steps therein) do not contain cleavable groups, except for those that can be cleaved under conditions that do not substantially damage and / or transform proteins. In some embodiments, cleavable groups include, but are not limited to, -S-, -SS-, -S-Cy-, -C(O)-O-, -C(O)-S-, an acetal moiety, -N=N-, an imine moiety, -CH=N-, a -P(O)(OR)O- moiety, -P(O)(OR)- is or contains an N(R)- moiety, an --C(O)-CH2-C(COOH)=CHC(O)- moiety, a -CHOH-CHOH- moiety, a -Se- moiety, Si bonded to two oxygen atoms, an -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO2-, an -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted at the o-position with -NO2-, or an -C(O)-N(-)- moiety in which N is a ring atom of a heteroaryl ring.In some embodiments, the cleavable group is or includes a -SS-, -S-CH2-Cy-, -S-Cy-, -C(O)-O-, -C(O)-S-, an acetal moiety, -N=N-, an imine moiety, -CH=N-, -P(O)(OR)O- moiety, -P(O)(OR)-N(R)- moiety, a -C(O)-CH2-C(COOH)=CHC(O)- moiety, a -CHOH-CHOH- moiety, a -Se- moiety, a Si bonded to two oxygen atoms, -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO2-, -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted at the o-position with -NO2-, or a -C(O)-N(-)- moiety where N is a ring atom of a heteroaryl ring. In some embodiments, the cleavage group is a cleavable linker or cleavable moiety described in US2020 / 0190165, each of which cleavable linkers and cleavable moieties are incorporated herein by reference. [ka] and During the ceremony, Wavy lines perpendicular to the bonds indicate possible cleavage sites; R 2a , R 2b and R 2c are the same or different, and each independently represents (i) a hydrogen atom or a halogen atom, (ii) a monovalent hydrocarbon group, (iii) aralkyl, (iv) a monovalent heterocyclic group, (v)R c -O-, R c -C(O)-, R c -OC(O)- or R c -C(O)-O-, , R c is hydrogen or a monovalent hydrocarbon group, (vi)-NR d R e , -NR d R e-C(O)-, -NR d R e -C(O)O-, -NR d -C(O)-, -NR d -C(O)O- or R d -C(O)-NR e -, R d and R e are the same or different and each is a hydrogen atom or a monovalent hydrocarbon radical; (vii) selected from the group consisting of a nitro group, a sulfate group, a sulfonate group, a cyano group, and a carboxyl group; J is -CH2-, -O-, or -S-; r is an integer from 1 to 4, The white and black circles are bonds that connect independently to other parts.

[0268] In some embodiments, the linker moiety does not contain a cleavage group as described above. In some embodiments, the linker moiety does not contain one or more, or any, of the following moieties: -S-, -SS-, -S-CH2-Cy-, -S-Cy-, -C(O)-O-, -C(O)-S-, acetal moiety, -N=N-, imine moiety, -CH=N-, -P(O)(OR)O- moiety, -P(O)(OR)-N(R)- moiety, --C(O)-CH2-C(COOH)=CHC(O)- moiety, -CHOH-CHOH- moiety, -Se- moiety, Si bonded to two oxygen atoms, -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO2-, -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO2- at the o-position, or a -C(O)-N(-)- moiety in which N is a ring atom of a heteroaryl ring. In some embodiments, the linker moiety does not contain one or more, or any, of the following moieties: -SS-, -S-CH2-Cy-, -S-Cy-, -C(O)-O-, -C(O)-S-, an acetal moiety, -N=N-, an imine moiety, -CH=N-, a -P(O)(OR)O- moiety, a -P(O)(OR)-N(R)- moiety, a -C(O)-CH2-C(COOH)=CHC(O)- moiety, a -CHOH-CHOH- moiety, a -Se- moiety, a Si bonded to two oxygen atoms, a -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO2-, a -C(O)-CH2- in which -CH2- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO2- at the o-position, or a -C(O)-N(-)- moiety in which N is a ring atom of a heteroaryl ring. In some embodiments, the linker moiety does not comprise -S-. In some embodiments, the linker moiety does not include -SS- (optionally excluding a disulfide moiety formed by two amino acid residues, and in some embodiments, optionally excluding a disulfide moiety formed by two cysteine ​​residues). In some embodiments, the linker moiety does not include -S-Cy-. In some embodiments, the linker moiety does not include -S-CH2-Cy-. In some embodiments, the linker moiety does not include -C(O)-O-.In some embodiments, the linker moiety does not comprise a —C(O)—S— moiety. In some embodiments, the linker moiety does not comprise an acetal moiety. In some embodiments, the linker moiety does not comprise a —N═N— moiety. In some embodiments, the linker moiety does not comprise an imine moiety. In some embodiments, the linker moiety does not comprise a —CH═N— moiety (optionally except within a ring, and in some embodiments, optionally except within a heteroaryl ring). In some embodiments, the linker moiety does not comprise a —P(O)(OR)O— moiety. In some embodiments, the linker moiety does not comprise a —P(O)(OR)—N(R)— moiety. In some embodiments, the linker moiety does not comprise a —C(O)—CH2—C(COOH)═CHC(O)— moiety. In some embodiments, the linker moiety does not comprise a —CHOH—CHOH— moiety. In some embodiments, the linker moiety does not comprise a —Se— moiety. In some embodiments, the linker moiety does not comprise a Si bonded to two oxygen atoms. In some embodiments, the linker moiety does not include -C(O)-CH-, where -CH- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO-. In some embodiments, the linker moiety does not include -C(O)-CH-, where -CH- is bonded to the benzyl carbon and the phenyl ring of the benzyl group is substituted with -NO- at the o-position. In some embodiments, the linker moiety does not include a -C(O)-N(-)- moiety, where N is a ring atom of a heteroaryl ring. In some embodiments, the linker moiety does not contain either of these groups. In some embodiments, L. RM is such a linker moiety. In some embodiments, L PM is such a linker moiety. In some embodiments, L LG is such a linker moiety. In some embodiments, the agents of the present disclosure do not contain one or more, or all, of such moieties.

[0269] In some embodiments, the drug does not contain a cleavable group, the cleavage of which can release LG, except optionally in one or more of RG. In some embodiments, the drug does not contain -SS-, acetal, or imine groups, except in RG or TBT. In some embodiments, the drug does not contain -SS-, acetal, or imine groups, except in cases where the drug may have -SS- formed by two amino acid residues. In some embodiments, the drug does not contain -SS-, acetal, or imine groups, except in cases where the drug may have -SS- formed by a cysteine ​​residue. In some embodiments, the drug does not contain -SS-, acetal, or imine groups.

[0270] In some embodiments, L is a covalent bond. In some embodiments, L is a divalent optionally substituted straight or branched C 1~100 In some embodiments, L is a divalent optionally substituted linear or branched C alkyl group, wherein one or more methylene units of the group are optionally and independently replaced. 6~100 In some embodiments, L is a divalent optionally substituted linear or branched C alkyl group having 1 to 20 heteroatoms, wherein one or more methylene units of the group are optionally and independently replaced. 5~100 In some embodiments, L is a divalent optionally substituted linear or branched C alkyl group having 1 to 20 heteroatoms, wherein one or more methylene units of the group are optionally and independently replaced. 1~100 It is a heteroaliphatic group, in which one or more methylene units of the group are optionally and independently replaced.

[0271] In some embodiments, the linker moiety (e.g., L) is or includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more) polyethylene glycol units. In some embodiments, the linker moiety is -(CH2CHO) n-, where n is as described herein. In some embodiments, one or more methylene units of L is independently -(CH2CH2O) n - has been replaced with

[0272] As described herein, in some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, n is 11. In some embodiments, n is 12. In some embodiments, n is 13. In some embodiments, n is 14. In some embodiments, n is 15. In some embodiments, n is 16. In some embodiments, n is 17. In some embodiments, n is 18. In some embodiments, n is 19. In some embodiments, n is 20.

[0273] In some embodiments, the linker moiety (e.g., L) is or includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more) amino acid residues. As used in this disclosure, "one or more" can be 1 to 100, 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more. In some embodiments, one or more methylene units of L are independently replaced with an amino acid residue. In some embodiments, one or more methylene units of L are independently replaced with an amino acid residue, wherein the amino acid residue is of Formula AI or a salt thereof. In some embodiments, one or more methylene units of L are independently replaced with an amino acid residue, each amino acid residue being independently selected from the group consisting of -N(R a1 )-La1 -C(R a2 )(R a3 )-L a2 It has the structure —CO— or a salt thereof.

[0274] In some embodiments, a linker moiety comprises one or more moieties (e.g., amino, carbonyl, etc.) that can be utilized to connect to other moieties. In some embodiments, a linker moiety comprises one or more -NR'-, where R' is as described in this disclosure. In some embodiments, -NR'- improves solubility. In some embodiments, -NR'- serves as a connection point to another moiety. In some embodiments, R' is -H. In some embodiments, one or more methylene units of L are independently replaced with -NR'-, where R' is as described in this disclosure.

[0275] In some embodiments, a linker moiety (e.g., L) comprises a -C(O)- group that can be used to connect to a moiety. In some embodiments, one or more methylene units of L are independently replaced with -C(O)-.

[0276] In some embodiments, a linker moiety (e.g., L) comprises an -NR'- group that can be used to connect moieties, in some embodiments, one or more methylene units of L are independently replaced with -N(R')-.

[0277] In some embodiments, a linker moiety (e.g., L) comprises a -C(O)NR'- group that can be used to connect moieties. In some embodiments, one or more methylene units of L are independently replaced with -C(O)N(R')-.

[0278] In some embodiments, a linker moiety (e.g., L) comprises a -C(R')2- group. In some embodiments, one or more methylene units of L are independently replaced with -C(R')2-. In some embodiments, -C(R')2- is -CHR'-. In some embodiments, R' is -(CH2)2C(O)NH(CH2) 11In some embodiments, R' is -COOH. In some embodiments, R' is -(CH2)2COOH. In some embodiments, R' is -COOH.

[0279] In some embodiments, the linker moiety is or includes one or more ring moieties, e.g., one or more methylene units of L are replaced with -Cy-. In some embodiments, the linker moiety (e.g., L) includes an aryl ring. In some embodiments, the linker moiety (e.g., L) includes a heteroaryl ring. In some embodiments, the linker moiety (e.g., L) includes an aliphatic ring. In some embodiments, the linker moiety (e.g., L) includes a heterocyclyl ring. In some embodiments, the linker moiety (e.g., L) includes a polycyclic ring. In some embodiments, the ring of the linker moiety (e.g., L) has 3 to 20 members. In some embodiments, the ring is 5 members. In some embodiments, the ring is 6 members. In some embodiments, the ring of the linker is the product of a cycloaddition reaction (e.g., click chemistry and variations thereof) utilized to link different moieties together.

[0280] In some embodiments, the linker moiety (e.g., L) is [ka] In some embodiments, the methylene units of L are or include: [ka] In some embodiments, a methylene unit of L is replaced with -Cy-. In some embodiments, -Cy- is [ka] is.

[0281] In some embodiments, a linker moiety (e.g., L) is or includes -CO)y-. In some embodiments, L is or includes -[(CH2)nO]mCy[(CH2)nO]mNH, or L is -[(CH2)nO]mCy[(CH2)nO]mNHC(O)[(CH2)nO]mNH-, or L is -[(CH2)nO]mCy[(CH2)nO]m{NHC(O)[(CH2)nO]m}pNH-, where n, m, and p are independently, at each occurrence, 1 to 20, 1 to 12, or 2 to 10. In some embodiments, each n is 2, and at each occurrence m is independently selected from an integer from 2 to 10, or in some embodiments, m is independently selected from an integer from 2 to 6, and Cy is [ka] In some embodiments, a methylene unit of L is replaced with -Cy-. In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] is.

[0282] In some embodiments, the linker moiety (e.g., L) of a provided agent (e.g., a compound of Table 1) is: [ka] In some embodiments, [ka] is the structure of [ka] or [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] is.

[0283] In some embodiments, the linker moiety is as described in Table 1. In some embodiments, L is an L described in this disclosure. 1 In some embodiments, L is any of the L groups described in this disclosure. b is.

[0284] In some embodiments, L RM is a covalent bond. In some embodiments, L RM is not a covalent bond. RM In some embodiments, L is or includes -(CHCHO)-. RM is or includes -(CH2)nO-(CH2CH2O)n-(CH2)n-, where each n is independently as described herein and each -CH2- is independently optionally substituted. In some embodiments, L RM is —(CH)O—(CHCHO)—(CH)—, where each n is independently as described herein and each —CH— is independently optionally substituted. In some embodiments, L RMis —(CH)—O—(CHCHO)—(CH)—, where n is as described herein, and each —CH— is independently optionally substituted. In some embodiments, L RM is —(CH 2 ) 2 —O—(CH 2 CH 2 O) n —(CH 2 ) 2 —, where n is as described herein.

[0285] In some embodiments, L PM is a covalent bond. In some embodiments, L PM is not a covalent bond. PM In some embodiments, L is or includes -(CHCHO)-. PM is or includes -(CH2)nO-(CH2CH2O)n-(CH2)n-, where each n is independently as described herein and each -CH2- is independently optionally substituted. In some embodiments, L PM is —(CH)O—(CHCHO)—(CH)—, where each n is independently as described herein and each —CH— is independently optionally substituted. In some embodiments, L PM is —(CH)—O—(CHCHO)—(CH)—, where n is as described herein, and each —CH— is independently optionally substituted. In some embodiments, L PM is —(CH 2 ) 2 —O—(CH 2 CH 2 O) n —(CH 2 ) 2 —, where n is as described herein.

[0286] In some embodiments, L PM (eg, in the product of a first agent and a second agent) is or includes the reaction product moiety that forms the first reactive moiety and the second reactive moiety.

[0287] In some embodiments, a linker moiety (e.g., L) in the product of the first drug and the second drug may be PM )teeth, [ka] In some embodiments, the methylene unit of the linker moiety (e.g., L) or L (e.g., L RM , L PM In some embodiments, the linker moiety, which may be -Cy-, is replaced with -Cy-. In some embodiments, -Cy- is optionally substituted [ka] In some embodiments, -Cy- is [ka] In some embodiments, L is -[(CH2)nO]mCH2Cy[(CH2)nO]m- or -. In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] is.

[0288] Cell receptor binding moiety Various receptor binding moieties according to embodiments of the present invention are described in WO2019 / 199621A1 published on October 17, 2019, WO2019 / 199634 published on October 17, 2019, International Application No. PCT / US2020 / 055053 filed on October 9, 2020, and International Application No. PCT / US2020 / 055053 filed on October 9, 2020, each of which is incorporated herein by reference in its entirety.

[0289] In certain embodiments, the cell receptor binding moiety may comprise an ASGPR binding group connected via an amine group. The term "asialoglycoprotein receptor (ASGPR) binding group" refers to a binding group that binds to a hepatocyte asialoglycoprotein receptor. This binding group is also a component of the bifunctional compounds described herein as cell receptor binding moieties that are covalently attached to an antibody binding moiety, either via a linker group or directly. The ASGPR group selectively binds to the hepatocyte asialoglycoprotein receptor on the surface of hepatocytes. It is through this moiety that the bifunctional compound complexed with a circulating protein (e.g., galactose-deficient IgA1) binds to the hepatocyte. Upon binding to the hepatocyte, the circulating protein is taken up by the hepatocyte or other cells via the phagocytic mechanism, and the circulating protein is degraded by lysosomal degradation.

[0290] The amine group may be a primary alkylamine group or a secondary alkylamine group, each of which is optionally substituted on the amine group with a C1-C3 alkyl group.

[0291] The cell receptor binding moiety has the following chemical structure: [ka] or [ka] and may comprise an ASGPR binding group according to where X is 1 to 4 atoms in length and is selected from O, S, N(R N1 ) or C(R N1 )(R N1 ) group, so that If X is one atom long, X is O, S, N(R N1 ) or C(R N1 )(R N1 ) and If X is two atoms long, not more than one atom of X may be O, S, or N(R N1 ) and If X is 3 or 4 atoms long, not more than two atoms of X may be O, S, or N(R N1) and R N1 is H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups; R1 and R3 each independently represent H, -(CH2) K OH, -(CH2) optionally substituted with 1 to 3 halo groups K OC1-C4 alkyl, C1-C4 alkyl optionally substituted with 1-3 halo groups, -(CH2) K -vinyl, O-(CH2) K -vinyl, -(CH2) K -alkynyl, -(CH2) K -COOH, -(CH2) optionally substituted with 1 to 3 halo groups K C(O)O-C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, O-C(O)-C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, -C(O)-C1-C4 alkyl; R1 and R3 are each independently optionally substituted with up to three halo groups; [ka] a C1-C4 alkyl group, each of the alkyl groups of which is optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxyl groups, or an O-C1-C4 alkyl group, each of which is optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxyl groups; K is independently an integer from 0 to 4, or R1 and R3 each independently represent the chemical structure: [ka] wherein R 7 is O-C1-C4 alkyl optionally substituted with 1-3 halo groups and 1 or 2 hydroxy groups, or R 7 is -NR N3 R N4Base or [ka] or R1 and R3 each independently represent the structure: [ka] or a group according to the following chemical structure: [ka] [ka] [ka] [ka] or R1 and R3 are each independently [ka] It is the basis, [ka] is a C3-C8 saturated carbocyclic group, R C is absent, H, C1-C4 alkyl optionally substituted with 1-3 halo groups or 1-2 hydroxyl groups, or the structure: [ka] wherein R4, R5 and R6 are each independently H, halo (F, Cl, Br, I), CN, NR N1 R N2 , -(CH2) K OH, optionally substituted with 1 to 3 halo groups, -(CH2) KO—C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, C1-C3 alkyl, optionally substituted with 1 to 3 halo groups, —O—C1-C3-alkyl, —(CH2) K COOH, optionally substituted with 1 to 3 halo groups -(CH2) K C(O)O-C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, O-C(O)-C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, -C(O)-C1-C4 alkyl; R C teeth, [ka] basis, [ka] base, [ka] basis, or [ka] It is the basis, R N , R N1 and R N2 are each independently H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups or 1 or 2 hydroxyl groups; K is independently an integer from 0 to 4; K' is an integer from 1 to 4, R N3 is H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups or 1 or 2 hydroxy groups; R N4 is H, a C1-C3 alkyl group optionally substituted with 1-3 halo groups or 1 or 2 hydroxy groups, or R N4 teeth, [ka] group, K is preferably 1, [ka] is a linker group comprising at least one glycan-specific IgG antibody moiety and linking the at least one glycan-specific IgG antibody moiety to the cell receptor binding moiety via an optional linker moiety; or [ka] is a linker group containing at least one or more functional groups that can be used to covalently attach the linker group to at least one glycan-specific IgG antibody moiety or an optional linker moiety; R2 is [ka] is a group, and R N1 and K are the same as above, R AM is H, a C1-C4 alkyl group optionally substituted with up to three halo groups and one or two hydroxyl groups, -(CH2) K COOH group, optionally substituted with 1 to 3 halo groups -(CH2) K C(O)O-C1-C4 alkyl group, optionally substituted with 1 to 3 haloF groups; O-C(O)-C1-C4 alkyl group, optionally substituted with 1 to 3 halo groups; -C(O)-C1-C4 alkyl group, optionally substituted with 1 to 3 halo groups; -(CH2) K -NR N3 R N4 group (in the formula, R N3 is H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups or 1 or 2 hydroxy groups; R N4 is H, a C1-C3 alkyl group optionally substituted with 1-3 halo groups or 1 or 2 hydroxy groups, or [ka] is a group or R2 is [ka] It is the basis, R TA H, CN, NR N1 R N2 , -(CH2) K OH, optionally substituted with 1 to 3 halo groups, -(CH2) K OC1-C4 alkyl, C1-C4 alkyl optionally substituted with 1 to 3 halo groups; -(CH2) K COOH, optionally substituted with 1 to 3 halo groups -(CH2) K C(O)O-C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, O-C(O)-C1-C4 alkyl, optionally substituted with 1 to 3 halo groups, -C(O)-C1-C4 alkyl; R TA is C3~C 10 aryl or a 3- to 10-membered heteroaryl group containing up to five heteroaryl atoms, each of which may optionally contain up to three (preferably one) CN, NR N1 R N2 , -(CH2) K OH, optionally substituted with 1 to 3 halo groups, -(CH2) K O—C1-C4 alkyl, optionally substituted with 1-3 halo groups or 1 or 2 hydroxy groups, C1-C3 alkyl, optionally substituted with 1-3 halo groups, —O—C1-C3-alkyl, —(CH2) K COOH, optionally substituted with 1 to 3 halo groups -(CH2) K C(O)O—C1-C4 alkyl, optionally substituted with 1-3 halo groups, OC(O)—C1-C4 alkyl, or —(CH2) optionally substituted with 1-3 halo groups. K substituted with C(O)-C1-C4 alkyl; RTA teeth, [ka] basis, [ka] basis, [ka] basis, [ka] group, optionally substituted with up to three C1-C3 alkyl groups optionally substituted with up to three halo groups [ka] is a group or R TA teeth, [ka] It is the basis, R N , R N1 and R N2 are each independently H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups or 1 or 2 hydroxyl groups, and each -(CH2) K the group is optionally substituted with 1 to 4, preferably 1 or 2, C1-C3 alkyl groups optionally substituted with 1 to 3 fluoro groups or 1 to 2 hydroxyl groups; K is independently 0 to 4.

[0292] The cell receptor binding moiety has the following chemical structure: [ka] or [ka] and may comprise an ASGPR binding group according to where X is 1 to 4 atoms in length and is selected from O, S, N(R N1 ) or C(R N1 )(R N1 ) group, so that If X is one atom long, X is O, S, N(R N1 ) or C(R N1 )(R N1 ) and If X is two atoms long, not more than one atom of X may be O, S, or N(R N1 ) and If X is 3 or 4 atoms long, not more than two atoms of X may be O, S, or N(R N1 ) and Each R N1 are independently H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups, preferably F (R N1 is preferably H or methyl, more often H), R1 and R3 are each independently H, -(CH2) K OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH2) K OC1-C4 alkyl, C1-C4 alkyl optionally substituted with 1-3 halo (F, Cl, Br, I, preferably F) groups, -(CH2) K Vinyl, O-(CH2) K vinyl, -(CH2) K Alkynyl, -(CH2) K COOH, -(CH2) optionally substituted with 1 to 3 halo, preferably F, groups K C(O)O-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; O-C(O)-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; or -C(O)-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; R1 and R3 are each independently optionally substituted with up to three (preferably one) halo groups (preferably F); [ka] groups, each of which is optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; or an O-C1-C4 alkyl group, each of which alkyl groups is optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups, and K is independently 0 to 4 (0, 1, 2, 3, or 4); or R1 and R3 each independently represent the chemical structure: [ka] wherein R 7 is O-C1-C4 alkyl optionally substituted with 1-3 halo groups, preferably F, and 1 or 2 hydroxy groups, or R 7 is -NR N3 R N4 Base or [ka] or R1 and R3 each independently represent the structure: [ka] or a group according to the following chemical structure: [ka] [ka] [ka] [ka] Or Or R1 and R3 are each independently [ka] It is the basis, [ka] is a C3-C8 saturated carbocyclic group, R C is absent, H, C1-C4 alkyl optionally substituted with 1-3 halo (preferably fluoro) groups or 1-2 hydroxyl groups, or the structure: [ka] wherein R4, R5 and R6 are each independently H, halo (F, Cl, Br, I), CN, NR N1 R N2 , -(CH2) K OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH2) K O—C1-C4 alkyl, optionally substituted with 1-3 halo (F, Cl, Br, I, preferably F) groups; C1-C3 alkyl, optionally substituted with 1-3 halo, preferably F groups; —O—C1-C3-alkyl; —(CH2) K COOH, -(CH2) optionally substituted with 1 to 3 halo, preferably F, groups K C(O)O-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; O-C(O)-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; or R C teeth, [ka] basis, [ka] basis, [ka] group, or [ka] It is the basis, R N , R N1 and R N2 are each independently H or a C1-C3 alkyl group optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; K is independently 0 to 4 (0, 1, 2, 3 or 4), preferably 0 or 1; K' is 1 to 4, preferably 1; R N3 is H or a C1-C3 alkyl group optionally substituted with 1-3 halo groups, preferably F, or 1 or 2 hydroxy groups; R N4 is H, a C1-C3 alkyl group optionally substituted with 1-3 halo groups, preferably F, or 1 or 2 hydroxy groups, or R N4 teeth, [ka] group, K is preferably 1, [ka] is a linker group comprising at least one glycan-specific IgG antibody moiety and linking the at least one glycan-specific IgG antibody moiety to the cell receptor binding moiety via an optional linker moiety; or [ka] is a linker group containing at least one or more functional groups that can be used to covalently attach the linker group to at least one glycan-specific IgG antibody moiety or an optional linker moiety; R2 is [ka] is a group, and R N1 and K are the same as above, RAM is H, C1-C4 alkyl optionally substituted with up to three halo groups (preferably F) and one or two hydroxyl groups, -(CH2) K COOH group, optionally substituted with 1 to 3 halo, preferably F, groups -(CH2) K C(O)O—C1-C4 alkyl group, an O-C(O)-C-C alkyl group optionally substituted with 1 to 3 halo, preferably F, groups; a -C(O)-C-C alkyl group optionally substituted with 1 to 3 halo, preferably F, groups; R N3 is H -(CH2) K -NR N3 R N4 a C1-C3 alkyl group optionally substituted with one to three halo groups, preferably F, or one or two hydroxy groups; R2 is [ka] It is the basis, R TA H, CN, NR N1 R N2 , -(CH2) K OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH2) K OC1-C4 alkyl, C1-C4 alkyl optionally substituted with 1-3 halo (F, Cl, Br, I, preferably F) groups, -(CH2) K COOH, -(CH2) optionally substituted with 1 to 3 halo, preferably F, groups K C(O)O-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; O-C(O)-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; -C(O)-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; or R TA is C3~C 10aryl or a 3- to 10-membered heteroaryl group containing up to five heteroaryl atoms, each of which may optionally contain up to three (preferably one) CN, NR N1 R N2 , -(CH2) K OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH2) K O—C1-C4 alkyl, C1-C3 alkyl optionally substituted with 1-3 halo (F, Cl, Br, I, preferably F) groups or 1 or 2 hydroxy groups, O—C1-C3-alkyl optionally substituted with 1-3 halo, preferably F groups, —(CH2) K COOH, -(CH2) optionally substituted with 1 to 3 halo, preferably F, groups K C(O)O-C1-C4 alkyl, optionally substituted with 1-3 halo, preferably F groups; OC(O)-C1-C4 alkyl, or -(CH2) optionally substituted with 1-3 halo, preferably F groups. K C(O)-C1-C4 alkyl, or R TA teeth, [ka] basis, [ka] basis, [ka] Base, or [ka] group, or R TA is optionally substituted with up to three, preferably one, C1-C3 alkyl group, which is optionally substituted with up to three halo (preferably F) groups [ka] group, or R TA teeth, [ka] It is the basis, R N , R N1 and R N2 are each independently H or a C1-C3 alkyl group optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; Each -(CH2) K the group is optionally substituted with 1 to 4, preferably 1 or 2, C1-C3 alkyl groups optionally substituted with 1 to 3 fluoro groups or 1 to 2 hydroxyl groups; K is independently 0 to 4 (0, 1, 2, 3 or 4), preferably 0 or 1; or A pharmaceutically acceptable salt, stereoisomer, solvate, or polymorph thereof.

[0293] In one embodiment, When X is two atoms long, X is -OC(R N1 )(R N1 ), C(R N1 )(R N1 )-O-, -SC(R N1 )(R N1 ), C(R N1 )(R N1 )-S-, N(R N1 )-C(R N1 )(R N1 ), C(R N1 )(R N1 )-N(R N1 ) or C(R N1 )(R N1 )-C(R N1 )(R N1 ) and When X is three atoms long, X is -OC(R N1 )(R N1 )-C(R N1 )(R N1)、C(R N1 )(R N1 )-OC(R N1 )(R N1 )-、 -OC(R N1 )(R N1 )-O-、-OC(R N1 )(R N1 )-S-、-OC(R N1 )(R N1 )-N(R N1 )-、 -SC(R N1 )(R N1 )-C(R N1 )(R N1 )、C(R N1 )(R N1 )-SC(R N1 )(R N1 )-、C(R N1 )(R N1 )-C(R N1 )(R N1 )-S、-SC(R N1 )(R N1 )-S-、-SC(R N1 )(R N1 )-O-、-SC(R N1 )(R N1 )-N(R N1 )-、N(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 )、C(R N1 )(R N1 )-N(R N1 )-C(R N1 )(R N1 )、C(R N1 )(R N1 )-C(R N1 )(R N1 )-N(R N1 )、N(R N1 )-C(R N1 )(R N1 )-N(R N1 ) or C(R N1 )(R N1 )-C(R N1 )(R N1 )-C(R N1 )(RN1 ) and When X is four atoms long, X is -OC(R N1 )(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 ), C(R N1 )(R N1 )-OC(R N1 )(R N1 )-(R N1 )(R N1 )-, -OC(R N1 )(R N1 )-OC(R N1 )(R N1 )-, -SC(R N1 )(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 )-, C(R N1 )(R N1 )-SC(R N1 )(R N1 )-C(R N1 )(R N1 )-, C(R N1 )(R N1 )-(R N1 )(R N1 )-SC(R N1 )(R N1 )-, -SC(R N1 )(R N1 )-SC(R N1 )(R N1 )-, N(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 )-, C(R N1 )(R N1 )-N(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 ), C(R N1 )(R N1 )-C(RN1 )(R N1 )-N(R N1 ), N(R N1 )-C(R N1 )(R N1 )-N(R N1 ), or C(R N1 )(R N1 )-C(R N1 )(R N1 )-C(R N1 )(R N1 ) and R N1 is the same as that shown in claim 4 or 6 above.

[0294] In one embodiment, X is OCH or CHO, and R N1 is H.

[0295] The cell receptor binding moiety has the following chemical structure: [ka] or [ka] and may comprise an ASGPR binding group according to wherein R1, R2 and R3 are the same as in claim 9, or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof.

[0296] The cell receptor binding portion has the following structure: [ka] or [ka] and In the formula, R A is a C1-C3 alkyl group optionally substituted with 1-5 halo (preferably fluoro) groups (preferably R A is a methyl or ethyl group optionally substituted with 1 to 3 fluoro groups), Z A is -(CH2) IM , -O-(CH2) IM , S-(CH2) IM , N.R. M -(CH2) IM , C(O)-(CH2) IM -, a PEG group containing 1 to 8, preferably 1 to 4, ethylene glycol residues, or I M and R M is the same as above -C(O)(CH2) IM NR M group (preferably a PEG-containing group containing 1 to 8 ethylene glycol residues, preferably 2 to 4 ethylene glycol residues), Z B does not exist or (CH2) IM , C(O)-(CH2) IM - or C(O)-(CH2) IM -NR M and IM and R M is the same as above.

[0297] In one embodiment, R A may be a methyl or ethyl group optionally substituted with 1 to 3 fluoro groups.

[0298] In one embodiment, Z A may be a PEG group containing 1 to 4 ethylene glycol residues.

[0299] In certain embodiments, the methyl or ethyl group may be substituted with 1 to 3 fluoro groups.

[0300] In certain embodiments, the ASGPR binding group may be N-acetyl-D-galactosamine.

[0301] In certain embodiments, the cell receptor binding moiety may be a low density lipoprotein receptor-related protein 1 (LRP1), a low density lipoprotein receptor (LDLR), an FcγRI binding group, an FcRN binding group, a transferrin receptor binding group, or a macrophage scavenger receptor binding group.

[0302] The present invention is further illustrated by the following non-limiting examples. [Example]

[0303] Proper protein aging and turnover are processes necessary for maintaining homeostasis. Newly synthesized proteins targeted for secretion are first trafficked to the endoplasmic reticulum, where they are post-translationally modified with N-linked glycan chains terminating in sialic acid. As proteins age, terminal sialic acid residues are removed by circulating endogenous glycosidases. This natural protein aging process unmasks galactose and N-acetylgalactose (GalNAc) residues that bind to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes. ASGPR is a C-type lectin that removes aged circulating proteins with exposed GalNAc residues from the circulation by trafficking them to lysosomes. Multiple galactose or GalNAc residues displayed on the protein surface are required for high-affinity binding to and subsequent endocytosis by the ASGPR. Once these proteins are endocytosed, they are released from the ASGPR by calcium depletion from the endosome and changes in binding site amino acid protonation due to a drop in pH, which then recycles the ASGPR back to the hepatocyte surface. Endocytosed proteins are trafficked to late endosomes, where they fuse with lysosomes. Lysosomal proteases then degrade the endocytosed proteins, permanently removing them from circulation (M).

[0304] Non-glycosylated proteins (e.g., immunoglobulins) are not known to be natural targets of ASGPR. One such protein is galactose-deficient IgA1 (Gd-IgA1), which has been shown to be involved in the pathophysiology of IgA nephropathy. We propose a bifunctional molecule for degrading circulating Gd-IgA1 that utilizes ASGPR as a pathway for protein entry into the endosomal-lysosomal degradation pathway.

[0305] Throughout this application, various publications are referenced by author name and date, or patent or patent publication number. The disclosures of these publications are incorporated by reference in their entireties into this application in order to more fully describe the state of the art known to those skilled in the art as of the date of the invention described and claimed herein. However, the citation of a reference herein should not be construed as an admission that such reference is prior art to the present invention.

[0306] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are encompassed by the following claims. For example, pharmaceutically acceptable salts other than those specifically disclosed in the description and examples herein may be used. Furthermore, it is contemplated that specific items within the list of items, or subsets of items within larger groups of items, may be combined with other specific items, subsets of items, or larger groups of items, regardless of the presence or absence of specific disclosure herein identifying such combinations.

Claims

1. A glycan-specific IgG antibody moiety; a cell receptor binding moiety that binds to hepatocytes or other lysed cells via the hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptors present on the surface of lysed cells in a patient or subject; A compound comprising: Optionally, a linker portion connecting the glycan-specific IgG antibody portion and the cell receptor binding portion; The compound.

2. The compound of claim 1 , wherein the glycan-specific IgG antibody portion is configured to bind to galactose-deficient IgA1 (Gd-IgA1).

3. The compound according to claim 1 or 2, wherein the glycan-specific IgG antibody moiety is a recombinant IgG antibody moiety (rIgG).

4. The compound according to claim 1 or 2, wherein the glycan-specific IgG antibody portion is isolated from serum of an IgA nephropathy patient.

5. Formula [AI]: 【Chemistry 1】 [A-I] [In the formula, Each of a and b is independently an integer of 1 or greater; each AT is a glycan-specific IgG antibody moiety or fragment thereof; L is a linker moiety; Each TBT is independently a cell receptor binding moiety that binds to hepatocytes or other degraded cells via the hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor on the surface of said degraded cells in a patient or subject. or a pharma- ceutically acceptable salt thereof.

6. 6. The compound of claim 5, wherein a is 1, b is 3, and each TBT contains an N-acetyl-D-galactosamine (GalNAc) moiety.

7. The glycan-specific IgG antibody portion comprises an IgG1 or a fragment thereof connected to the linker L at an amino acid residue selected from K246 and K248 of the IgG1 heavy chain and their corresponding amino acid residues; or The glycan-specific IgG antibody portion comprises an IgG2 or a fragment thereof connected to the linker L at an amino acid residue selected from K251 and K253 of an IgG2 heavy chain and their corresponding amino acid residues; or The glycan-specific IgG antibody portion comprises an IgG4 or a fragment thereof connected to the linker L at an amino acid residue selected from K239 and K241 of the IgG4 heavy chain and their corresponding amino acid residues; 7. A compound according to claim 5 or 6.

8. L is a covalent bond or one or more aliphatic, aryl, heteroaromatic groups having 1 to 20 heteroatoms, or any combination thereof, optionally substituted, linear or branched, divalent or polyvalent C １～１００ one or more methylene units of said group are independently １～６ Alkylene, C １～６ Alkenylene, -C≡C-, -Cy-, -C(R') ２ -, -O-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R') ２ N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S )(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R') ２ -C(R') ２ -) ｎ ]-, where n is 1 to 20; Cy is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, each monocyclic ring independently being selected from the group consisting of C ３～２０ Alicyclic ring, C ６～２０ an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms; Each R' is independently -R, -C(O)R, -CO ２ R or -SO ２ R, and each R is independently -H or an optionally substituted group selected from C1-30 aliphatic, C1-30 heteroaliphatic having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, C6-30 aryl, C6-30 arylaliphatic, C6-30 arylheteroaliphatic having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; The two R groups may independently be taken together to form a covalent bond, or two or more R groups on the same atom may independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two or more R groups on two or more atoms may independently be taken together with their intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; The compound according to any one of claims 5 to 7.

9. The linker may be one or more -[(CH ２ ) ｎ -O] ｍ -, wherein each n is independently 1 to 20, and m is 1 to 100.

10. The compound of any one of claims 1 to 9, wherein the cell receptor binding moiety comprises an ASGPR binding group connected via an amine group.

11. The amine group is a primary alkylamine group or a secondary alkylamine group, each of which has on the amine group: １ ~C ３ The compound according to claim 10, which is optionally substituted with an alkyl group.

12. The cell receptor binding moiety has the chemical structure: 【Chemistry 2】 or 【Chemistry 3】 and an ASGPR binding group according to where X is 1-4 atoms in length and is selected from O, S, N(R Ｎ１ ) or C(R Ｎ１ ) (R Ｎ１ ) groups, such that When X is one atom long, X is O, S, N (R Ｎ１ ) or C(R Ｎ１ ) (R Ｎ１ ) and When X is two atoms long, not more than one atom of X is O, S, or N (R Ｎ１ ) and When X is 3 or 4 atoms long, not more than two atoms of X are O, S, or N (R Ｎ１ ) and R Ｎ１ is H or C optionally substituted with 1 to 3 halo groups; １ ~C ３ is an alkyl group, R １ and R ３ are each independently H, -(CH ２ ) Ｋ OH, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo groups １ ~C ４ Alkyl, -(CH ２ ) Ｋ -vinyl, O-(CH ２ ) Ｋ -vinyl, -(CH ２ ) Ｋ -Alkynyl, -(CH ２ ) Ｋ -COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ alkyl, O—C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ alkyl, —C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ is alkyl, or R １ and R ３ are each independently optionally substituted with up to three halo groups. 【Chemistry 4】 a C group, each of whose alkyl groups may be substituted with 1 to 3 halo groups or 1 or 2 hydroxyl groups; １ ~C ４ an O--C alkyl group, each of which may be substituted with 1 to 3 halo groups or 1 or 2 hydroxyl groups; １ ~C ４ is an alkyl group, K is independently an integer from 0 to 4; R １ and R ３ each independently represent the chemical structure: 【Chemistry 5】 where R ７ is an O—C group optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxy groups; １ ~C ４ alkyl or R ７ is -NR Ｎ３ R Ｎ４ Base or 【Chemistry 6】 or R １ and R ３ each independently have the structure: 【Chemistry 7】 or a group according to the following chemical structure: 【Chemistry 8】 【Chemistry 9】 【Chemistry 10】 or R １ and R ３ are each independently 【Chemistry 11】 It is based on 【Chemistry 12】 is C ３ ~C ８ is a saturated carbocyclic group, R Ｃ is absent or optionally substituted with H, 1 to 3 halo groups, or 1 to 2 hydroxyl groups; １ ~C ４ Alkyl, or the structure: 【Chemistry 13】 where R ４ , R ５ and R ６ are each independently H, halo (F, Cl, Br, I), CN, NR Ｎ１ R Ｎ２ , -(CH ２ ) Ｋ OH, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo groups １ ~C ３ Alkyl, —O—C optionally substituted with 1 to 3 halo groups １ ~C ３ -Alkyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ alkyl, O—C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ alkyl, —C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ is alkyl, or R Ｃ teeth, 【Chemistry 14】 basis, 【Chemistry 15】 basis, 【Chemistry 16】 Base, or 【Chemistry 17】 It is based on R Ｎ , R Ｎ１ and R Ｎ２ are each independently H or C optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxyl groups; １ ~C ３ is an alkyl group, K is independently an integer from 0 to 4; K′ is an integer from 1 to 4, R Ｎ３ is H or C optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxy groups; １ ~C ３ is an alkyl group, R Ｎ４ is H or C optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxy groups; １ ~C ３ is an alkyl group or R Ｎ４ teeth, 【Chemistry 18】 group, K is preferably 1, 【Chemistry 19】 is a linker group comprising at least one glycan-specific IgG antibody moiety and linking said at least one glycan-specific IgG antibody moiety to said cell receptor binding moiety via an optional linker moiety; or 【Chemistry 20】 is a linker group that contains at least one or more functional groups that can be used to covalently attach the linker group to at least one glycan-specific IgG antibody moiety or an optional linker moiety; R ２ teeth, 【Chemistry 21】 group, R Ｎ１ and K are the same as above, R ＡＭ is H, C optionally substituted with up to three halo groups and one or two hydroxyl groups; １ ~C ４ Alkyl group, -(CH ２ ) Ｋ COOH group, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ an alkyl group, O—C(O)—C optionally substituted with 1 to 3 haloF groups; １ ~C ４ an alkyl group, —C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ Alkyl group, -(CH ２ ) Ｋ -NR Ｎ３ R Ｎ４ group (in the formula, R Ｎ３ is H or C optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxy groups; １ ~C ３ is an alkyl group, R Ｎ４ is H, C optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxy groups; １ ~C ３ an alkyl group, or 【Chemical 22】 or R ２ teeth, 【Chemistry 23】 It is based on R ＴＡ H, CN, NR Ｎ１ R Ｎ２ , -(CH ２ ) Ｋ OH, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo groups １ ~C ４ Alkyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ alkyl, O—C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ alkyl, —C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ is alkyl, or R ＴＡ is C ３ ~C １０ aryl or a 3-10 membered heteroaryl group containing up to 5 heteroaryl atoms, each of said aryl or heteroaryl groups containing up to 3 (preferably 1) CN, NR Ｎ１ R Ｎ２ , -(CH ２ ) Ｋ OH, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo groups, or 1 or 2 hydroxy groups １ ~C ３ Alkyl, —O—C optionally substituted with 1 to 3 halo groups １ ~C ３ -Alkyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ alkyl, O—C(O)—C optionally substituted with 1 to 3 halo groups; １ ~C ４ -(CH ２ ) Ｋ C(O)-C １ ~C ４ may be substituted with alkyl, or R ＴＡ teeth, 【Chemistry 24】 basis, 【Chemistry 25】 basis, 【Chemistry 26】 basis, 【Chemical 27】 group, up to three C optionally substituted with up to three halo groups １ ~C ３ Optionally substituted with an alkyl group 【Chemistry 28】 or R ＴＡ teeth, 【Chemical 29】 It is based on R Ｎ , R Ｎ１ and R Ｎ２ are each independently H or C optionally substituted with 1 to 3 halo groups or 1 or 2 hydroxyl groups; １ ~C ３ is an alkyl group, each -(CH ２ ) Ｋ The group is optionally substituted with 1 to 4, preferably 1 or 2, 1 to 3 fluoro groups or 1 to 2 hydroxyl groups. １ ~C ３ may be substituted with an alkyl group, and K is independently 0 to 4; A compound according to any one of claims 1 to 11.

13. The cell receptor binding moiety has the chemical structure: 【Chemistry 30】 or 【Chemistry 31】 or a pharma- ceutically acceptable salt, stereoisomer, solvate, or polymorph thereof, where X is 1-4 atoms in length and is selected from the group consisting of O, S, N(R Ｎ１ ) or C(R Ｎ１ ) (R Ｎ１ ) group, the result, When X is one atom long, X is O, S, N (R Ｎ１ ) or C(R Ｎ１ ) (R Ｎ１ ) and When X is two atoms long, not more than one atom of X is O, S, or N (R Ｎ１ ) and When X is 3 or 4 atoms long, not more than two atoms of X are O, S, or N (R Ｎ１ ) and Each R Ｎ１ are independently H or C optionally substituted with 1 to 3 halo groups, preferably F; １ ~C ３ is an alkyl group (R Ｎ１ is preferably H or methyl, more frequently H); R １ and R ３ are each independently H, -(CH ２ ) Ｋ OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo (F, Cl, Br, I, preferably F) groups １ ~C ４ Alkyl, -(CH ２ ) Ｋ Vinyl, O-(CH ２ ) Ｋ Vinyl, -(CH ２ ) Ｋ Alkynyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ O—C(O)—C, optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ -C(O)-C optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ is alkyl, or R １ and R ３ each independently may be substituted with up to three (preferably one) halo groups (preferably F). 【Chemistry 32】 groups, each of which may be substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; １ ~C ４ an alkyl group, or each of the alkyl groups being optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; １ ~C ４ an alkyl group, and K is independently 0 to 4 (0, 1, 2, 3, or 4); R １ and R ３ each independently having the chemical structure: 【Chemical 33】 where R ７ is O—C optionally substituted with 1 to 3 halo groups, preferably F, and 1 or 2 hydroxy groups; １ ~C ４ alkyl or R ７ is -NR Ｎ３ R Ｎ４ Base, or 【Chemical 34】 or R １ and R ３ each independently having the structure: 【Chemistry 35】 or a group according to the following chemical structure: 【Chemical 36】 【Chemical 37】 【Chemical Formula 38】 【Chemical 39】 or Or R １ and R ３ However, each independently, 【Chemistry 40】 It is based on 【Chemistry 41】 is C ３ ~C ８ is a saturated carbocyclic group, R Ｃ is absent or optionally substituted with H, 1 to 3 halo (preferably fluoro) groups, or 1 to 2 hydroxyl groups; １ ~C ４ Alkyl, or the structure: 【Chemistry 42】 where R ４ , R ５ and R ６ are each independently H, halo (F, Cl, Br, I), CN, NR Ｎ１ R Ｎ２ , -(CH ２ ) Ｋ OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo (F, Cl, Br, I, preferably F) groups １ ~C ３ -OC optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ３ -Alkyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ O—C(O)—C, optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ -C(O)-C optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ is alkyl, or R Ｃ teeth, 【Chemistry 43】 basis, 【Chemistry 44】 basis, 【Chemistry 45】 Group, or 【Chemistry 46】 It is based on R Ｎ , R Ｎ１ and R Ｎ２ are each independently H or C optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; １ ~C ３ is an alkyl group, K is independently 0 to 4 (0, 1, 2, 3 or 4), preferably 0 or 1; K' is 1 to 4, preferably 1; R Ｎ３ is H or C optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxy groups; １ ~C ３ is an alkyl group, R Ｎ４ is H, 1 to 3 halo groups, preferably F, or C optionally substituted with 1 or 2 hydroxy groups; １ ~C ３ is an alkyl group or R Ｎ４ teeth, 【Chemistry 47】 group, K is preferably 1, 【Chemistry 48】 is a linker group comprising at least one glycan-specific IgG antibody moiety, said linker group linking said at least one glycan-specific IgG antibody moiety to said cell receptor binding moiety via an optional linker moiety; or 【Chemistry 49】 is a linker group that contains at least one or more functional groups that can be used to covalently attach the linker group to at least one glycan-specific IgG antibody moiety or an optional linker moiety; R ２ teeth, 【Chemistry 50】 group, R Ｎ１ and K are the same as above, R ＡＭ is C optionally substituted with H, up to three halo groups (preferably F), and one or two hydroxyl groups; １ ~C ４ Alkyl, -(CH ２ ) Ｋ COOH group, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ O—C(O)—C, optionally substituted with an alkyl group, 1 to 3 halo groups, preferably F groups １ ~C ４ -C(O)-C, optionally substituted with an alkyl group, 1 to 3 halo, preferably an F group １ ~C ４ Alkyl group, R Ｎ３ is H - (CH ２ ) Ｋ -NR Ｎ３ R Ｎ４ C optionally substituted with a group, or 1 to 3 halo groups, preferably F, or 1 or 2 hydroxy groups; １ ~C ３ is an alkyl group, or R ２ teeth, 【Chemistry 51】 It is based on R ＴＡ H, CN, NR Ｎ１ R Ｎ２ , -(CH ２ ) Ｋ OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo (F, Cl, Br, I, preferably F) groups １ ~C ４ Alkyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ O—C(O)—C, optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ -C(O)-C optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ alkyl or R ＴＡ is C ３ ~C １０ aryl or a 3-10 membered heteroaryl group containing up to 5 heteroaryl atoms, each of said aryl or heteroaryl groups containing up to 3 (preferably 1) CN, NR Ｎ１ R Ｎ２ , -(CH ２ ) Ｋ OH, optionally substituted with 1 to 3 halo (F, Cl, Br, I, preferably F) groups, -(CH ２ ) Ｋ O.C. １ ~C ４ C optionally substituted with alkyl, 1 to 3 halo (F, Cl, Br, I, preferably F) groups or 1 or 2 hydroxy groups １ ~C ３ O—C optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ３ -Alkyl, -(CH ２ ) Ｋ COOH, -(CH ２ ) Ｋ C(O)O-C １ ~C ４ O—C(O)—C, optionally substituted with alkyl, 1 to 3 halo, preferably F groups １ ~C ４ -(CH) optionally substituted with alkyl or 1 to 3 halo, preferably F groups ２ ) Ｋ C(O)-C １ ~C ４ may be substituted with alkyl, or R ＴＡ teeth, 【Chemistry 52】 basis, 【Chemistry 53】 basis, 【Chemical 54】 Base, or 【Chemistry 55】 or R ＴＡ is up to three, preferably one, C optionally substituted with up to three halo (preferably F) groups; １ ~C ３ Optionally substituted with an alkyl group 【Chemistry 56】 or R ＴＡ teeth, 【Chemistry 57】 It is based on R Ｎ , R Ｎ１ and R Ｎ２ are each independently H or C optionally substituted with 1 to 3 halo groups, preferably F, or 1 or 2 hydroxyl groups; １ ~C ３ is an alkyl group, Each -(CH ２ ) Ｋ The group is optionally substituted with 1 to 4, preferably 1 or 2, 1 to 3 fluoro groups or 1 to 2 hydroxyl groups. １ ~C ３ may be substituted with an alkyl group, K is independently 0 to 4 (0, 1, 2, 3 or 4), preferably 0 or 1; A compound according to any one of claims 1 to 11.

14. When X is two atoms long, X is -O-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-O-, -S-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-S-, N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ) or C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ) and When X is three atoms long, X is -O-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-O-C(R Ｎ１ ) (R Ｎ１ ) -, -O-C(R Ｎ１ ) (R Ｎ１ )-O-, -OC(R Ｎ１ ) (R Ｎ１ ) -S-, -OC(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ) -, -S-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-S-C(R Ｎ１ ) (R Ｎ１ ) -, C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-S, -S-C(R Ｎ１ ) (R Ｎ１ )-S-, -S-C(R Ｎ１ ) (R Ｎ１ )-O-, -S-C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ) -, N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ), N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ) or C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ) and When X is 4 atoms long, X is -O-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-O-C(R Ｎ１ ) (R Ｎ１ ) - (R Ｎ１ ) (R Ｎ１ ) -, -O-C(R Ｎ１ ) (R Ｎ１ )-O-C(R Ｎ１ ) (R Ｎ１ ) -, -S-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ) -, C(R Ｎ１ ) (R Ｎ１ )-S-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ) -, C(R Ｎ１ ) (R Ｎ１ ) - (R Ｎ１ ) (R Ｎ１ )-S-C(R Ｎ１ ) (R Ｎ１ ) -, -S-C(R Ｎ１ ) (R Ｎ１ )-S-C(R Ｎ１ ) (R Ｎ１ ) -, N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ) -, C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ), C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ), N(R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-N(R Ｎ１ ), or C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ )-C(R Ｎ１ ) (R Ｎ１ ) and R Ｎ１ is the same as that shown in claim 12 or 13 above, 14. A compound according to claim 12 or 13.

15. X is OCH ２ or CH ２ O and R Ｎ１ The compound according to claim 12 or 13, wherein is H.

16. The cell receptor binding moiety has the chemical structure: 【Chemistry 58】 or 【Chemistry 59】 or a pharma- ceutically acceptable salt, stereoisomer, solvate, or polymorph thereof, In the formula, R １ , R ２ and R ３ is the same as claim 12. A compound according to any one of claims 1 to 11.

17. The cell receptor binding moiety has the following structure: 【Chemistry 60】 or 【Chemistry 61】 having In the formula, R Ａ is C optionally substituted with 1 to 5 halo (preferably fluoro) groups; １ ~C ３ is an alkyl group (preferably R Ａ is a methyl or ethyl group optionally substituted with 1 to 3 fluoro groups); Z Ａ is -(CH ２ ) ＩＭ , —O—(CH ２ ) ＩＭ , S-(CH ２ ) ＩＭ , N.R. Ｍ - (CH ２ ) ＩＭ , C(O)-(CH ２ ) ＩＭ -, a PEG group containing 1 to 8, preferably 1 to 4, ethylene glycol residues, or IM and R Ｍ is the same as above -C(O)(CH ２ ) ＩＭ N.R. Ｍ group (preferably a PEG-containing group containing 1 to 8 ethylene glycol, preferably 2 to 4 ethylene glycol residues); Z Ｂ does not exist or (CH ２ ) ＩＭ , C(O)-(CH ２ ) ＩＭ - or C(O)-(CH ２ ) ＩＭ -NR Ｍ and IM and R Ｍ is the same as above, 17. The compound of claim 16.

18. R Ａ The compound according to claim 17, wherein is a methyl or ethyl group optionally substituted with 1 to 3 fluoro groups.

19. Z Ａ is a PEG group containing 1 to 4 ethylene glycol residues.

20. The compound of claim 18, wherein the methyl or ethyl group is substituted with 1 to 3 fluoro groups.

21. The compound of claim 16, wherein the ASGPR binding group is N-acetyl-D-galactosamine.

22. 10. The compound of any one of claims 1 to 9, wherein the cell receptor binding moiety is a low density lipoprotein receptor-related protein 1 (LRP1), a low density lipoprotein receptor (LDLR), an FcγRI binding group, an FcRN binding group, a transferrin receptor binding group, or a macrophage scavenger receptor binding group.

23. A pharmaceutical composition comprising a compound according to any one of claims 1 to 22.

24. An antibody-binding portion, a cell receptor binding moiety that binds to hepatocytes or other lysed cells via the hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptors present on the surface of lysed cells in a patient or subject; A compound comprising: and optionally a linker moiety connecting the antibody-binding moiety and the cell receptor-binding moiety. The compound.

25. Formula [A-II]: 【Chemistry 62】 [A-II] or a pharma- ceutically acceptable salt thereof, During the ceremony, Each of a and b is independently an integer of 1 or greater; each AT is an antibody binding moiety, L is a linker moiety; Each TBT is independently a cell receptor binding moiety that binds to hepatocytes or other degraded cells via a hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor present on the surface of the degraded cells in a patient or subject.

25. The compound of claim 24.

26. 26. The compound of claim 25, wherein a is 1 and b is 3.

27. The compound according to any one of claims 24 to 26, wherein the antibody-binding moiety comprises a peptide moiety that binds to a specific amino acid residue of a glycan-specific IgG antibody.

28. the peptide portion that binds to a specific amino acid residue of the antibody, 【Chemistry 63】 And, 【Chemistry 64】 However, A-1 to A-50 shown in the table below: 【Table 1-1】 【Table 1-2】 【Table 1-3】 【Table 1-4】 【Table 1-5】 【Table 1-6】 【Table 1-7】 【Table 1-8】 28. The compound of claim 27 selected from:

29. the antibody comprises an IgG1 or a fragment thereof connected to the linker moiety L at an amino acid residue selected from K246 and K248 of an IgG1 heavy chain and amino acid residues corresponding thereto; or the antibody comprises an IgG2 or a fragment thereof connected to the linker moiety L at an amino acid residue selected from K251 and K253 of an IgG2 heavy chain and amino acid residues corresponding thereto; or The antibody comprises an IgG4 or a fragment thereof connected to the linker moiety L at an amino acid residue selected from K239 and K241 of an IgG4 heavy chain and amino acid residues corresponding thereto. The compound according to any one of claims 24 to 28.

30. further comprising a reactive group RG connected to said linker moiety; RG is a group represented by the formula -L ＬＧ２ , -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ - or -L ＲＧ１ -L ＲＧ２ - group, L ＬＧ２ is -NH-, -NHCO-, -(CH ２ ) ｎ -NHCO-, -(CH ２ ) ｎ -OCO-, -(CH ２ ) ｎ -OCONH-, -C(O)-NHCH ２ -, -C(O)-NHCH ２ CH ２ -, -C(O)O-CH ２ (-), or NH-C(O)O-CH ２ (-), and L ＬＧ３ is an optionally substituted aryl ring, L ＬＧ４－ is a bond, —NH— or —O—, L ＲＧ１ -O-C(O)-, -C(O)-, -S(O)-, -OS(O) ２ -, or -OP(O(OR)-, L ＲＧ２ is -CH ２ -C(O)-, -C(O)- or -CH ２ - and L ＬＧ is -(O)C-[(CH ２ ), ｎ O] ｍ (CH ２ ), ｎ NH-, -(O)C-[(CH ２ ), ｎ O] ｍ (CH ２ ), ｎ NH-, -[(CH ２ ), ｎ O] ｍ NH C(O)[(CH ２ ), ｎ O] ｍ NH-, -[(CH ２ ), ｎ O] ｍ {NH C(O)[(CH ２ ), ｎ O] ｍ}{{END]] ｐ NH-, -[(CH ２ ), ｎ O] ｍ Cy[(CH ２ ), ｎ O] ｍ NH-, -[(CH ２ ), ｎ O] ｍ Cy[(CH ２ ), ｎ O] ｍ NH C(O)[(CH ２ ), ｎ O] ｍ NH-, or -[(CH ２ ), ｎ O] ｍ Cy[(CH ２ ), ｎ O] ｍ {NH C(O)[(CH ２ ), ｎ O] ｍ}{pNH- and wherein n, m, and p at each occurrence are integers independently selected from 1 to 12, and Cy is an optionally substituted cyclic group.

30. A compound according to any one of claims 1 to 22 and 24 to 29.

31. RG is a group represented by the formula -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ Based on 【Chemistry 65】 31. The compound of claim 30, selected from:

32. 31. The compound of claim 30, wherein n is 2 at each occurrence.

33. 31. The compound of claim 30, wherein the reactive group is or includes -C(O)-O- or -O-C(O)-.

34. 34. The compound of claim 33, wherein the reactive group further comprises an aryl group optionally attached to -C(O)-O- or -O-C(O)-, the aryl group being substituted with one or more electron-withdrawing groups.

35. The aryl group is 【Chemistry 66】 The structure is In the formula, R ｓ represents independently at each occurrence a halogen, -NO ２ , -F, -LR', -C(O)-LR', -S(O)-LR', -S(O) ２ -L-R', and -P(O)(-L-R') ２ and R' is selected from H or C １ ~C ６ is alkyl, 35. The compound of claim 34.

36. the linker group comprises a reactive group; wherein, upon contact with an antibody, the reactive group reacts with a group on the antibody, conjugating the cell receptor binding moiety to the antibody, optionally via a linker. The compound according to any one of claims 24 to 35.

37. The reactive group is 【Chemistry 67】 is or contains wherein -C(O)- is connected to the antibody binding moiety, optionally via a linker; 37. The compound of claim 36.

38. The compound according to claim 24, wherein the linker moiety does not comprise a reactive group according to any one of claims 30 to 34.

39. Formula [A-III]: LG-RG-L ＲＭ (-TBT) ｂ 、 [A-III] or a salt thereof, During the ceremony, LG is a compound having the structure R ＬＧ -L ＬＧ and wherein the antibody binding moiety has the formula: R ＬＧ teeth, 【Chemistry 68】 , R ｃ -(Xaa)z-, IVIG, a nucleic acid moiety, or a small molecule moiety; each Xaa is independently a residue of an amino acid or amino acid analog; t is 0 to 50; z is 1 to 50; Each R ｃ are independently -L ａ -R', Each of a and b is independently 1 to 200; Each L ａ are independently a covalent bond or C １ ~C ２０ Aliphatic or C having 1 to 5 heteroatoms １ ~C ２０ an optionally substituted divalent group selected from heteroaliphatic, one or more methylene units of said group are independently selected from C(R') ２ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ may be replaced by -N(R')-, -C(O)S-, or -C(O)O-; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently ３～２０ Alicyclic ring, C ６～２０ an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms; L ＬＧ Is, -L ＬＧ１ -, -L ＬＧ１ -L ＬＧ２ -, -L ＬＧ１ -L ＬＧ２ -L ＬＧ３ - or -L ＬＧ１ -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ - and RG is, -L ＲＧ１ -L ＲＧ２ -, -L ＬＧ４ -L ＲＧ１ -L ＲＧ２ -, -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ -L ＲＧ２ - or -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ -L ＲＧ２ - and L ＬＧ１ , L ＬＧ２ , L ＬＧ３ , L ＬＧ４ , L ＲＧ１ , L ＲＧ２ , and L ＲＭ each is independently L; Each L is independently a covalent bond or a divalent, optionally substituted, straight chain or branched C alkyl group that contains one or more aliphatic moieties, aryl moieties, heteroaliphatic moieties each independently having 1 to 20 heteroatoms, heteroaromatic moieties each independently having 1 to 20 heteroatoms, or any combination of any one or more of such moieties. １～１００ one or more methylene units of said group are independently １～６ Alkylene, C １～６ Alkenylene, divalent C having 1 to 5 heteroatoms １～６ Heteroaliphatic groups, -C≡C-, -Cy-, -C(R') ２ -, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R') ２ N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S )(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R') ２ -C(R') ２ -) ｎ ]- (wherein n is 1 to 20), Each R' is independently -R, -C(O)R, -CO ２ R or -SO ２ R, Each R is independently -H or C １～３０ Aliphatic, C with 1-10 heteroatoms １～３０ Heteroaliphatic, C ６～３０ Aryl, C ６～３０ Arylaliphatic, C with 1-10 heteroatoms ６～３０ an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms, and 3-30 membered heterocyclyl having 1-10 heteroatoms; or The two R groups may independently be taken together to form a covalent bond, or two or more R groups on the same atom may independently combine with said atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to said atom, 0-10 heteroatoms; or two or more R groups on two or more atoms may independently, together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to said intervening atoms, 0-10 heteroatoms; Each TBT is a cell receptor binding moiety that binds to hepatocytes or other degraded cells via a hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor present on the surface of the degraded cells in a patient or subject.

25. The compound of claim 24.

40. The antibody binding moiety comprises: (i) DCAWHLGELVWCT, or a salt form thereof, in which two C residues are linked by -S-S-; or (ii) DCAWHLGELVWCT, or a salt form thereof, wherein the N-terminus is capped with R-C(O)-; or (iii) DCAWHLGELVWCT, or a salt form thereof, wherein the N-terminus is capped with R-C(O)-, and R is methyl; or (iv) DCAWHLGELVWCT, or a salt form thereof, wherein the antibody binding portion is attached to the remainder of the molecule through its C-terminus. comprising or having the structure A compound according to any one of claims 24 to 29, 38 and 39.

41. The antibody binding portion is A-1 to A-50: 【Table 2-1】 【Table 2-2】 【Table 2-3】 【Table 2-4】 【Table 2-5】 【Table 2-6】 【Table 2-7】 【Table 2-8】 41. The compound of any one of claims 24-29 and 38-40, comprising or having a structure selected from:

42. L is a covalent bond or a divalent, optionally substituted, linear or branched aliphatic group or a heteroaliphatic group having 1 to 10 heteroatoms; One or more methylene units of said group are independently -C≡C-, -Cy-, -C(R') ２ -, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R') ２ N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S )(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R') ２ -C(R') ２ -) ｎ ]- (wherein n is 1 to 20), 26. The compound of claim 25.

43. LG is R ＬＧ -L ＬＧ - and R ＬＧ is or comprises a target binding moiety, L ＬＧ L ＬＧ１ , L ＬＧ１ -L ＬＧ２ -, L ＬＧ１ -L ＬＧ２ -L ＬＧ３ - or L ＬＧ１ -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ - and Each L ＬＧ is independently selected from L; 40. The compound of claim 39.

44. RG is -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ -L ＲＧ１ , --L ＬＧ２ -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ -L ＲＧ２ -, -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ -L ＲＧ２ -, L ＬＧ４ -L ＲＧ１ -L ＲＧ２ - or -L ＲＧ１ -L ＲＧ２ - or containing L ＬＧ１ is a covalent bond, -(CH ２ CH ２ O) n-, or -(CH ２ )n-O-(CH ２ CH ２ O)n-(CH ２ ) n-, L ＬＧ２ is a covalent bond, -NR'-, -C(O)-, -NR'C(O)-, -(CH ２ )n-OC(O)N(R')-, -CH ２ N (CH ２ CH ２ CH ２ S (O) ２ OH)-C(O)-, -C(O)-NHCH ２ -, -C(O)O-CH ２ -, or -NH-C(O)O-CH ２ - or containing R' is H or C １ ~C ６ is alkyl, L ＬＧ３ may be bonded to —C(O)—, L ＬＧ３ is a covalent bond or a substituted phenyl ring substituted with one or more substituents, the one or more substituents being independently an electron withdrawing group; L ＬＧ３ teeth, 【Chemistry 69】 and R Ｓ is F or NO ２ and L ＬＧ４ is a covalent bond, —O—, or —NR′—; L ＲＧ１ is a covalent bond, -S(O) ２ - or -C(O)-, L ＲＧ２ -C(O)-, -C(O)O-, -C(O)N(R')-, -S(O)-, -S(O) ２ -, -P(O)(OR')-, -P(O)(SR')-, or -P(O)(N(R') ２ )- or containing Each n is independently 1 to 10, and each -CH ２ - is independently optionally substituted; 40. The compound of claim 39.

45. L ＬＧ３ but, 【Chemistry 70】 and Each R Ｓ But F or NO ２ That is, 40. The compound of claim 39.

46. L ＲＧ２ But, -L ＲＧ３ -C (=CR ＲＧ１ R ＲＧ２ )-CR ＲＧ３ R ＲＧ４ -or-L ＲＧ３ -C(=CHR ＲＧ２ )-CHR ＲＧ４ - or containing R ＲＧ１ , R ＲＧ２ , R ＲＧ３ and R ＲＧ４ Each of is independently -LR', and L ＲＧ３ -C(O)-, -C(O)O-, -C(O)N(R')-, -S(O)-, -S(O) ２ -, -P(O)(OR')-, -P(O)(SR')-, or -P(O)(N(R') ２ ) - is 40. The compound of claim 39.

47. -L ＬＧ２ -L ＬＧ３ -L ＬＧ４ -L ＲＧ１ -が、 【Chemistry 71】 40. The compound of claim 39, wherein the compound is selected from the structure:

48. The compound according to any one of claims 24 to 29 and 38 to 47, wherein the antibody binding moiety is a glycan-specific IgG antibody binding moiety.

49. The pharmaceutical composition of claim 23 for removing galactose-deficient IgA1 in a patient or subject in need of removal of galactose-deficient IgA1.

50. The pharmaceutical composition of claim 23 for treating a disease state and / or condition associated with upregulation of galactosyl IgA1 in a patient or subject in need of treatment of the disease state and / or condition associated with upregulation of galactosyl IgA1.

51. 51. The pharmaceutical composition of claim 50, wherein the disease state and / or condition associated with upregulation of galactosyl IgA1 is an autoimmune disease.

52. 52. The pharmaceutical composition of claim 51, wherein the autoimmune disease is IgA nephropathy.

53. The pharmaceutical composition of claim 23 for treating an autoimmune disease in a patient in need of such treatment.

54. 54. The pharmaceutical composition of claim 53, wherein the autoimmune disease is IgA nephropathy.

55. An antibody portion, and a first compound comprising a cell receptor binding moiety that binds to hepatocytes or other degraded cells via a hepatocyte asialoglycoprotein (ASGPR) receptor or other cell receptor on the surface of degraded cells of a patient or subject, the first compound, optionally including a linker moiety connecting the antibody portion and the cell receptor binding portion; at least one additional compound comprising a moiety capable of binding to the antibody that forms the antibody portion of the first compound; 13. A pharmaceutical composition comprising:

56. The first compound has the formula [A-I]: 【Chemical Formula 72】 [A-I] The structure is wherein AT, L, TBT, a and b are as defined in claim 5.

56. The pharmaceutical composition of claim 55.

57. The at least one additional agent is represented by formula [A-III]: LG-RG-L ＲＭ (-TBT) ｂ [A-III] , Formula [A-IV]: LG-RG-H [A-IV] or a combination thereof, In the formula, LG, RG, and L ＲＭ is the same as that described in claim 39, 57. A pharmaceutical composition according to claim 55 or 56.

58. AT is a glycan-specific IgG antibody moiety; TBT is N-acetylgalactosamine (GalNAc); a is 1, and b is 3; 57. The pharmaceutical composition of claim 56.

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