Hydrazinyl-indole compounds and methods for producing a conjugate

• US 10,314,919 B2
• Filed: 10/31/2017
• Issued: 06/11/2019
• Est. Priority Date: 11/16/2012
• Status: Active Grant

• Current Assignee: Redwood Bioscience, Inc (Catalent, Inc.)
• Original Assignee: Redwood Bioscience, Inc (Catalent, Inc.)
• Inventors: Kudirka, Romas Alvydas, Albers, Aaron Edward, Barfield, Robyn M., Rabuka, David
• Primary Examiner(s): Coleman, Brenda L
• Application Number:
  US15/799,846
• Publication Number:
  US 20180104351A1
• Time in Patent Office: 588 Days
• CPC Class Codes: A61K 47/545 Heterocyclic compounds A61K47/558 takes precedence
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/68033 the drug being a maytansine
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: 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
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0058 Antibodies
• CPC Class Codes: G01N 33/582 with fluorescent label

Abstract

The present disclosure provides conjugate structures (e.g., polypeptide conjugates) and hydrazinyl-indole compounds used to produce these conjugates. The disclosure also provides methods of production of such conjugates, as well as methods of using the same.

Claims

1. A method of producing a conjugate, the method comprising:

combining in a reaction mixture;

(i) a compound of formula (IV);

2. The method of claim 1, wherein the second compound is a polypeptide.

3. The method of claim 1, wherein the reactive group comprises a reactive aldehyde group or a reactive ketone group.

4. The method of claim 1, wherein the reaction mixture comprises water.

5. The method of claim 1, wherein the reaction mixture has a pH of 7.

6. The method of claim 1, wherein the reaction conditions are at a temperature of 37°

C.

7. The method of claim 1, wherein n is 1.

8. The method of claim 1, wherein R₂ and R₃ are each independently selected from alkyl and substituted alkyl.

9. The method of claim 1, wherein R₂ and R₃ are each methyl.

10. The method of claim 1, wherein X₁, X₂, X₃ and X₄ are each C.

11. The method of claim 1, wherein Y₁, Y₂, Y₃ and Y₄ are each H.

12. The method of claim 1, wherein L is present and comprises a group selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, acyl amino, alkylamide, substituted alkylamide, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl.

13. The method of claim 1, wherein L is present and comprises a polymer.

14. The method of claim 13, wherein the polymer is a polyethylene glycol.

15. The method of claim 1, wherein the detectable label comprises a fluorophore.

16. The method of claim 1, wherein the compound is a compound of formula (V):

17. The method of claim 1, wherein the compound is a compound of formula (Va):