Granted Patent B2

US 12,503,498 · App. 17/065,729 · Granted Dec 23, 2025

Inventors: Clark Pan (Sutton, MA); Huawei Qiu (Westborough, MA)

Assignee: GENZYME CORPORATION

C07K16/00A61K47/68031A61K47/6811A61K47/6851A61K47/6889A61K49/0002A61K49/0004C07K16/18C07K16/2809C07K16/2851C07K16/2893C07K16/32C07K16/40A61K2039/505C07K2317/41C07K2317/52C07K2317/522C07K2317/71C07K2317/73

Abstract

Claims (19)

1 . A method of treating a neoplastic disorder in a patient in need thereof comprising administering an effective amount of an isolated antibody or antigen binding fragment thereof comprising an Fc domain with altered glycosylation, wherein the Fc domain comprises: an asparagine residue at amino acid position 298, according to EU numbering; and a serine or threonine residue at amino acid position 300, according to EU numbering, and wherein the antibody or antigen binding fragment thereof has a lower affinity for an Fcγ receptor than an antibody or antigen binding fragment thereof having a native Fc domain.

2 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof further comprises an alanine residue at amino acid position 299, according to EU numbering.

3 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof further comprises a glutamine residue at amino acid position 297, according to EU numbering.

4 . The method of claim 1 , wherein a side chain of the asparagine residue is linked to a glycan though a β-glycosylamide linkage.

5 . The method of claim 4 , wherein the glycan is a biantennary glycan.

6 . The method of claim 1 , wherein the Fcγ receptor is FcγRI and/or FcγRIIIa.

7 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof has a similar affinity for an FcRn receptor as a antibody or antigen binding fragment thereof having a native Fc domain.

8 . The method of claim 4 , wherein the glycan comprises a reactive aldehyde group.

9 . The method of claim 4 , wherein the glycan comprises an oxidized saccharide residue comprising a reactive aldehyde group wherein the oxidized saccharide residue is a terminal sialic acid or galactose.

10 . The method of claim 4 , wherein the glycan is linked to an effector moiety.

11 . The method of claim 4 , wherein the effector moiety is a cytotoxin or a detection agent, wherein the cytotoxin is selected from the group of cytotoxins depicted below:

wherein R 1 =alkyl, aryl, alkoxy, aryloxy, R 2 , R 3 =alkyl, aryl.

12 . The method of claim 10 , wherein the effector moiety is linked through an oxime or hydrazone linkage to a saccharide residue of the glycan.

13 . The method of claim 12 , wherein the saccharide residue is a terminal sialic acid or galactose residue of the glycan.

14 . The method of claim 10 , wherein the effector moiety comprises a pH-sensitive linker, disulfide linker, enzyme-sensitive linker or other cleavable linker moiety.

15 . The method of claim 10 , wherein the effector moiety comprises a linker moiety selected from the group of linker moieties depicted below:

wherein R 1 , R 2 , R 3 , R 4 , and R 5 is H, alkyl, or aryl.

16 . A method of treating a neoplastic disorder in a patient in need thereof comprising administering an effective amount of an isolated antibody or antigen binding fragment thereof comprising a Fc domain, wherein the Fc domain comprises: a free asparagine residue at amino acid position 298, according to EU numbering, and a free serine or threonine residue at amino acid position 300, according to EU numbering.

17 . A method of treating a neoplastic disorder in a patient in need thereof comprising administering an effective amount of an isolated antibody or antigen binding fragment thereof comprising a human IgG1 Fc domain, wherein the Fc domain comprises: a modified asparagine residue at amino acid position 298, according to EU numbering; and a free serine or threonine residue at amino acid position 300, according to EU numbering.

Assignments (1)

Continuity (8)

References Cited (400)