CN-121985967-A - Agents and methods for targeted delivery to cells

Abstract

The present invention relates to agents and methods for targeted delivery of payloads to cells. The payload comprises various molecules, such as therapeutic or diagnostic agents, in particular toxins, immunomodulators or radiodiagnostic agents. In some embodiments, the invention relates to providing a subject with a compound comprising a payload moiety and at least two tags (tag conjugate) and a compound that binds to a tag of the tag conjugate and a target antigen (e.g., a cell surface antigen on a target cell) (a docking compound).

Inventors

• U. Shaxin
• DONG ZHENGXIN
• J. I. McDonald
• F. Vohidov
• J. P. Bogen
• H-u. Schmidt
• J. Westhube lausch

Assignees

• 百欧恩泰欧洲股份公司

Dates

Publication Date

20260505

Application Date

20240802

Priority Date

20230904

Claims (20)

1. 1. A kit, comprising: (i) A compound comprising a binding moiety that binds to a target antigen and a binding moiety for a tag, or a nucleic acid encoding said compound, and (Ii) A compound comprising a payload portion and at least two tags, the binding portion for a tag being bound to the at least two tags, Wherein the tag is a peptide tag.
2. 2. The kit of claim 1, wherein the compound in (ii) contains a moiety comprising a polymer.
3. 3. The kit of claim 1 or 2, wherein the payload moiety and the peptide tag are coupled by a moiety comprising a polymer.
4. 4. A kit according to claim 2 or 3, wherein the polymer is not a polymer of protein-forming amino acids or D-isomers thereof.
5. 5. A kit, comprising: (i) A compound comprising a binding moiety that binds to a target antigen and a binding moiety for a tag, or a nucleic acid encoding said compound, and (Ii) A compound comprising a payload portion and at least two tags, the binding portion for a tag being bound to the at least two tags, Wherein the compound of (ii) further comprises a moiety comprising a polymer, wherein the polymer is not a polymer of a protein-forming amino acid or D-isomer thereof.
6. 6. The kit of claim 5, wherein the payload moiety and the tag are coupled through a moiety comprising a polymer, wherein the polymer is not a polymer of a protein-generating amino acid or D-isomer thereof.
7. 7. The kit of claim 5 or 6, wherein the tag is a peptide tag.
8. 8. The kit of any one of claims 2-7, wherein the polymer is selected from the group consisting of poly (ethylene glycol) (PEG), poly sarcosine (pSar) (poly (N-methylglycine)), polyoxazoline (POX), polyoxazine (POZ), and poly-2- (2- (2-aminoethoxy) ethoxy) acetic acid (pAEEA), derivatives, and combinations thereof.
9. 9. The kit of any one of claims 2-8, wherein the polymer comprises at least one poly-2- (2- (2-aminoethoxy) ethoxy) acetic acid (pAEEA) moiety or derivative thereof.
10. 10. The kit of any one of claims 1-9, wherein the payload moiety and the tag are coupled by a moiety comprising at least one poly-2- (2- (2-aminoethoxy) ethoxy) acetic acid (pAEEA) moiety or derivative thereof.
11. 11. The kit of any one of claims 1-10, wherein the nucleic acid is RNA.
12. 12. The kit of any one of claims 1-11, wherein the compound in (ii) comprises two of said tags.
13. 13. The kit of any one of claims 1-12, wherein the compound in (ii) comprises a payload moiety and a tag in a non-branched (linear) configuration.
14. 14. The kit of any one of claims 1-13, wherein the compound in (ii) comprises the formula: P-L A -T-L B -T Or (b) P-L A -T-L B -T-L C -P Wherein the method comprises the steps of P contains a payload portion; T comprises a tag; l A comprises a linking moiety; L B contains a linking moiety, and L C contains a linking moiety.
15. 15. The kit of claim 14, wherein one or more of L A 、L B and L C comprises a poly-2- (2- (2-aminoethoxy) ethoxy) acetic acid (pAEEA) moiety or derivative thereof.
16. 16. The kit of claim 14 or 15, wherein L B comprises a poly-2- (2- (2-aminoethoxy) ethoxy) acetic acid (pAEEA) moiety or derivative thereof.
17. 17. The kit of any one of claims 14-16, wherein L A and/or L C comprise an enzyme cleavage site.
18. 18. The kit of any one of claims 14-17, wherein one or more of L A 、L B and L C comprises the formula [ AEEA ] u -[L D -[AEEA] v ] w , Wherein the method comprises the steps of AEEA is 2- (2- (2-aminoethoxy) ethoxy) acetic acid or a derivative thereof; L D comprises a linking moiety; u is an integer of 2 or more; each v is an integer of 2 or more, and W is an integer of 1 to 4; Wherein the method comprises the steps of The different groups [ L D -[AEEA] v ] may be the same or different.
19. 19. The kit of any one of claims 14-18, wherein L B comprises a formula [ AEEA ] u -[L D -[AEEA] v ] w , Wherein the method comprises the steps of AEEA is 2- (2- (2-aminoethoxy) ethoxy) acetic acid or a derivative thereof; L D comprises a linking moiety; u is an integer of 2 or more; each v is an integer of 2 or more, and W is an integer of 1 to 4; Wherein the method comprises the steps of The different groups [ L D -[AEEA] v ] may be the same or different.
20. 20. The kit according to claim 18 or 19, wherein u and v are each integers from 2 to 10.

Description

Agents and methods for targeted delivery to cells Technical Field The present invention relates to agents and methods for targeted delivery of payloads to cells. The payload includes various molecules, such as therapeutic or diagnostic agents, in particular toxins, immunomodulators or radiodiagnostic agents. In some embodiments, the invention relates to providing a subject with a compound comprising a payload moiety and at least two tags (tag conjugate) and a compound that binds to a tag of the tag conjugate and a target antigen (e.g., a cell surface antigen on a target cell) (a docking compound). In some embodiments, the docking compound comprises a peptide or polypeptide. In some embodiments, the docking compound comprises a binding moiety that binds to the target cell (primary targeting moiety) and an additional binding moiety that binds to the tag of the tag conjugate. The tags of the tag conjugates can bind to their binding moiety on the docking compound, and the primary targeting moiety of the docking compound can bind to a target antigen on a target cell, such as an antigen on a cancer cell, thereby accurately delivering the payload to the target cell. In some embodiments, the docking compound is provided to the subject by administering a nucleic acid (e.g., RNA) encoding the docking compound. In some embodiments, the docking compound is provided to the subject by administering the docking compound. In some embodiments, the preformed complex is provided to the subject by administration, wherein the docking compound is conjugated to the tag conjugate. Background In many areas of medical treatment and diagnosis, it is desirable to selectively deliver an agent, such as a therapeutic (drug) or diagnostic (e.g., imaging agent), to specific cells within a subject, such as a patient. Active targeting of cells can be achieved by conjugation of the desired payload, either directly or indirectly, to a targeting moiety that binds to a cell surface antigen on the target cell of interest. The targeting moiety is typically a construct having affinity for a cell surface target (e.g., a membrane protein) and includes an antibody or antibody fragment. The present invention relates to a method wherein a docking compound is used that binds to a target cell (e.g., by binding to a cell surface antigen). The docking compound further comprises a moiety that binds to the compound comprising the payload and is equipped with at least two tags targeted by the moiety on the docking compound. In some embodiments, the docking compound bound to the tag conjugate comprising the payload is administered in the form of a nucleic acid encoding the docking compound for expression of the docking compound in the subject. The docking compound may bind to the target cell, e.g., by binding to a cell surface antigen, resulting in targeting of the payload. Common examples of pairs of interacting moieties on the docking compound and tag conjugate are antibody/tag systems. The concepts described herein allow for the use of a single type of tag conjugate to target a wide range of target cells, i.e., by using a single type of tag conjugate in combination with different docking compounds targeting different primary targets. The concepts described herein have further advantages in that primary targeting using a single docking compound can be performed in combination with different tag conjugates comprising different payloads. Disclosure of Invention The present invention relates to agents and methods for targeted delivery of payloads to cells. In some embodiments, the payload comprises a diagnostic compound, such as a radioisotope, or a therapeutic compound, such as a toxin or an immunomodulatory agent. Targeted delivery of a payload is achieved using a tag conjugate described herein, comprising a payload and a docking compound bound to the tag conjugate by its tag, the docking compound comprising a targeting molecule for targeting an antigen on a target cell. In one aspect, the invention relates to a kit comprising: (i) A compound comprising a binding moiety that binds to a target antigen and a binding moiety (a binding moiety for a tag) for a tag, or a nucleic acid encoding said compound, and (Ii) A compound comprising a payload portion and at least two tags, the binding portion for a tag being bound to the at least two tags, Wherein the tag is a peptide tag. In some embodiments, the compound in (ii) contains a moiety comprising a polymer. In some embodiments, the payload moiety and the peptide tag are coupled through a polymer-containing moiety. In some embodiments, the polymer is not a polymer of protein-forming (proteinogenic) amino acids or D-isomers thereof. In one aspect, the invention relates to a kit comprising: (i) A compound comprising a binding moiety that binds to a target antigen and a binding moiety for a tag, or a nucleic acid encoding said compound, and (Ii) A compound comprising a payload portion and at least two tags, the binding