Modified amino acids

Patent metadata

Field	Value
Publication number	US-9994527-B2
Application number	US-201715604106-A
Country	US
Kind code	B2
Filing date	May 24, 2017
Priority date	Aug 31, 2012
Publication date	Jun 12, 2018
Grant date	Jun 12, 2018

Abstract

Provided herein are modified amino acids comprising an azido group, polypeptides, antibodies and conjugates comprising the modified amino acids, and methods of producing the polypeptides, antibodies and conjugates comprising the modified amino acids. The polypeptides, antibodies and conjugates are useful in methods of treatment and prevention, methods of detection and methods of diagnosis.

First claim

What is claimed is:

1. A polypeptide which is a polymer of amino acid residues where one or more amino acid residues is according to the following formula IIc:

or a salt thereof, wherein W 4 is C 1 -C 10 alkylene, wherein R is -(a 1,2,3-triazol-1-ylene moiety)-(payload) where the 1,2,3-triazol-1-ylene moiety is bonded to W 4 through a nitrogen atom of the 1,2,3-triazolylene and the 1,2,3-triazol-1-ylene moiety is bonded to the payload through another atom in the 1,2,3-triazol-1-ylene moiety, and wherein the payload comprises a carbohydrate.

2. A polypeptide which is a polymer of amino acid residues where one or more amino acid residues comprises the compound according to the following formula:

or a salt thereof, wherein W 4 is C 1 -C 10 alkylene, wherein R′ is -(a 1,2,3-triazol-1-ylene moiety)-(linker)-(payload), where the 1,2,3-triazol-1-ylene moiety is bonded to W 4 through a nitrogen atom of the 1,2,3-triazolylene and the 1,2,3-triazol-1-ylene moiety is bonded to the linker through another atom in the 1,2,3-triazol-1-ylene moiety, and wherein the payload comprises a carbohydrate.

3. The polypeptide of claim 2 , wherein the linker comprises a polyethylene glycol.

4. A conjugate prepared by contacting an alkyne-containing payload with a polypeptide which is a polymer of amino acid residues where one or more amino acid residues is according to formula IIa:

or a salt thereof, wherein W 4 is C 1 -C 10 alkylene, and wherein the alkyne-containing payload comprises a carbohydrate, wherein the polypeptide and the payload are linked, after the contacting, via a moiety comprising a 1,2,3-triazole which is formed by the reaction of the N 3 group and the alkyne.

5. The conjugate of claim 4 , wherein the one or more amino acid residues of formula IIa is according to:

or a salt thereof.

6. The conjugate of claim 4 , wherein the moiety further comprises a linker comprising a polyethylene glycol.

7. The conjugate of claim 4 , wherein the alkyne-containing payload comprises a residue of DBCO according to the following formula:

8. A method for producing a conjugate, comprising:
a) combining an alkyne-containing carbohydrate, which optionally comprises a linker between the alkyne and the carbohydrate, with a polypeptide which is a polymer of amino acid residues where one or more amino acid residues is according to formula IIa:

or a salt thereof, wherein W 4 is C 1 -C 10 alkylene.

9. The method of claim 8 , further comprising a step before a) wherein the step comprises reacting a carbohydrate with periodate and reacting the resulting molecule comprising the carbohydrate with a reagent to generate the alkyne-containing carbohydrate.

10. The method of claim 9 , wherein the reagent comprises a residue of DBCO according to the following formula:

11. The method of claim 8 , wherein the one or more amino acid residues of formula IIa is according to:

or a salt thereof.

12. The method of claim 8 , further comprising a step before a) wherein the step comprises reacting a molecule comprising a carbohydrate with a reagent to generate the alkyne-containing carbohydrate.

13. The method of claim 12 , wherein the one or more amino acid residues of formula IIa is according to:

or a salt thereof.

14. The method of claim 12 , wherein the reagent comprises a residue of DBCO according to the following formula:

15. The method of claim 13 , wherein the reagent comprises a residue of DBCO according to the following formula:

Assignees

• Sutro Biopharma Inc

Inventors

• Stafford Ryan
• Thanos Christopher D
• Yang Wenjin

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07K14/535

  Granulocyte CSF; Granulocyte-macrophage CSF · CPC title

• C07C247/04

  being saturated · CPC title