US 11,865,183 B2
Conjugates and conjugating reagents comprising a linker that includes at least two (−CH2—CH2—O—) units in a ring
Antony Godwin, London (GB); Andrew Kyle, Cambridge (GB); and Nicholas Evans, Cambridge (GB)
Assigned to POLYTHERICS LIMITED, Cambridge (GB)
Filed by POLYTHERICS LIMITED, Cambridge (GB)
Filed on Feb. 3, 2022, as Appl. No. 17/591,621.
Application 17/591,621 is a continuation of application No. 16/092,768, granted, now 11,273,224, previously published as PCT/GB2017/051044, filed on Apr. 13, 2017.
Claims priority of application No. 1606543.5 (GB), filed on Apr. 14, 2016.
Prior Publication US 2022/0193249 A1, Jun. 23, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 31/404 (2006.01); A61K 31/5365 (2006.01); A61K 47/65 (2017.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61K 31/10 (2006.01); A61K 31/407 (2006.01); C07K 16/28 (2006.01); C07K 16/40 (2006.01); A61K 39/00 (2006.01); A61K 31/40 (2006.01)
CPC A61K 47/6803 (2017.08) [A61K 31/40 (2013.01); A61K 31/407 (2013.01); A61K 47/54 (2017.08); A61K 47/545 (2017.08); A61K 47/60 (2017.08); A61K 47/65 (2017.08); A61K 47/6867 (2017.08); A61K 47/6871 (2017.08); C07K 16/2878 (2013.01); C07K 16/40 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01)] 6 Claims
 
1. A conjugate comprising a protein or peptide conjugated to a therapeutic agent via a linker, characterised in that the linker includes a unit of the formula ˜(CH2—CH2—O—)x˜ within a ring, in which x is a number from 2 to 50, said ring being attached via a single tethering atom within the ring to the rest of the linker, or said ring being attached via two tethering atoms within the ring to the rest of the linker at a single point, wherein the conjugate is formed from conjugation of said protein or peptide with a reagent represented schematically by the formula:

OG Complex Work Unit Chemistry
in which:
D represents said therapeutic agent;
each T independently represents a tethering atom in the ring;
PEG represents said unit of the formula ˜(CH2—CH2—O—)x˜ within a ring, in which x is a number from 2 to 50; and
F represents a functional group for bonding to said protein or peptide wherein the functional group is a maleimide or derivative thereof according to one of the following formulae:

OG Complex Work Unit Chemistry
wherein the nitrogen atom of the maleimide ring is connected to the linker and L represents a leaving group.