# US 2024/0197889 A1 · Process for the preparation of pegylated drug-linkers and intermediates thereof

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- Number: US 2024/0197889 A1
- Document ID: US20240197889A1
- Status: Published application
- Kind: A1
- Application number: 18/462,325
- Filed: 2023-09-06
- Published: 2024-06-20
- Earliest claimed: 2016-03-25
- Assignees: Seagen Inc.
- Applicants: Seagen Inc.
- Inventors: Yunyu MAO; Philip MOQUIST; Anusuya CHOUDHURY; Wendel DOUBLEDAY
- Web page: https://patentgrep.com/patent/US20240197889A1

## CPC

- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61K 38/07: Tetrapeptides
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6883: {Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides improved processes for the preparation of auristatin drug-linkers with a PEG unit, as well as intermediates thereof.

## Claims

### Claim at position 1

-44. (canceled)

### Claim 45

A composition comprising Antibody Drug Conjugates represented by Formula 12 and Formula 12A, optionally in pharmaceutically acceptable salt form, having the structures of:
respectively, wherein
Ab is an antibody;
S is a sulfur atom from the antibody;
the Ab-S— moeity is attached to the carbon atom a or R to the carboxylic acid functional group;
D is an auristatin Drug Unit;
L1, L2 and L3, independently are selected from the group consisting of optionally substituted C1-C20 alkylene, optionally substituted C4-C20 heteroalkylene, optionally substituted C3-C8 carbocyclo, optionally substituted C6-C10 arylene, optionally substituted C5-C10 heteroarylene and optionally substituted C3-C8 heterocyclo;
RC is a PEG Capping Unit;
subscript n ranges from 2 to 24; and
subscript p ranges from about 1 to about 16,
wherein the composition contains no more than 10 wt. % Formula 12A Antibody Drug Conjugate, or
the Formula 12 and Formula 12A Antibody drug Conjugates, optionally in pharmaceutically acceptable salt form, have the structures of:
respectively, wherein the variable groups have their previous meanings and wherein the composition contains no more than 10 wt. % of Formula 12A Antibody Drug Conjugate.

### Claim 46 (depends on 45)

The composition or compound of claim 45, wherein the auristatin Drug Unit has the structure of Formula DF/E-3:
wherein
R13 is isopropyl or —CH2—CH(CH3)2; and
R19B is —CH(CH3)—CH(OH)Ph, —CH(CO2H)CH2Ph, —CH(CH2Ph)-2-thiazole, —CH(CH2Ph)-2-pyridyl, —CH(CH2-p-Cl-Ph), —CH(CO2Me)-CH2Ph, —CH(CO2Me)-CH2CH2SCH3, CH(CH2CH2SCH3)C(═O)NH-3-quinolyl, or —CH(CH2Ph)C(═O)NH-p-Cl-Ph, or
D has the structure of:

### Claim 47 (depends on 45)

The composition of claim 45, wherein Formula 12 and Formula 12A Antibody Drug Conjugates, optionally in pharmaceutically acceptable salt form, have the structures of:
respectively, or the Formula 12 and Formula 12A Antibody Drug Conjugates, optionally in pharmaceutically acceptable salt form, have the structures of:
respectively, each having the indicated carbon atom (*) predominately in the S configuration, and or in which subscript p is about 8.

### Claim 48 (depends on 47)

The composition of claim 47, wherein the antibody is capable of selectively binding to a tumor associated antigen.

### Claim 49 (depends on 48)

The composition of claim 48, wherein the tumor associated antigen is comprised of an extracellular domain of a cell-surface protein or glycoprotein to which the antibody is capable of binding, or
wherein the tumor associated antigen is a cell-surface protein or glycoprotein of an abnormal cell, wherein the cell-surface protein or glycoprotein is capable of internalization upon binding by an Antibody Drug Conjugate compound of the composition.

### Claim 50

(canceled)