Glycoengineered binding protein compositions

Patent metadata

Field	Value
Publication number	US-2018298093-A1
Application number	US-201815912494-A
Country	US
Kind code	A1
Filing date	Mar 5, 2018
Priority date	Nov 15, 2013
Publication date	Oct 18, 2018
Grant date	—

Abstract

Provided are glycoengineered populations of Fc domain-containing binding proteins with a reduced anti-drug immune response (ADA). Also provided are methods of treating disease using such compositions, and methods and host for making such compositions.

First claim

1 . A glycoengineered binding protein composition comprising a population of Fc domain-containing binding proteins having an G/M ratio of at least 10:1, wherein the total percent amount of G1 and G2 glycoforms in the population is more than 50%, wherein the total percent amount of M3-M9 glycoforms is less than 10%, wherein Fc domain containing binding proteins of the composition comprise the same polypeptide sequence, and wherein the glycoengineered binding protein composition exhibits a lower ADA response and/or a greater serum half-life than a non-hypergalactosylated population of Fc domain-containing binding proteins.

2 . The composition of claim 1 , wherein the total percent amount of G1 and G2 glycoforms in the population is more than 80%, or more than 99%.

3 . The composition of claim 1 , wherein less than 5%, or less than 1%, or less than 0.1% of the Fc domain-containing binding proteins in the population comprise M3-M9 glycoforms.

4 . The composition of claim 1 , wherein the population of Fc domain-containing binding proteins has a G1/2:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.

5 . The composition of claim 1 , wherein the population of Fc domain-containing binding proteins has a GS:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.

6 . The composition of claim 1 , wherein the population of Fc domain-containing binding proteins has a Gtotal:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.

7 . The composition of claim 1 , wherein the Fc domain-containing binding proteins in the population comprises an antigen-binding portion of an antibody or wherein the Fc domain-containing binding proteins in the population comprise a non-antibody antigen-binding portion, wherein the antigen-binding portion binds to tumor necrosis factor alpha (TNFα).

8 .- 10 . (canceled)

11 . The composition of claim 7 , wherein the population of Fc domain-containing binding proteins comprises the polypeptide sequence of adalimumab or a variant thereof, wherein the variant of adalimumab is D2E7SS22 and comprises the heavy chain variable region sequence of SEQ ID NO:1 and the light chain variable region sequence of the light chain of SEQ ID NO:2.

12 .- 16 . (canceled)

17 . The composition of claim 1 , wherein the composition is obtained from a cultured mammalian host cell line, wherein the host cell line is a CHO cell line containing a heterologous galactosyltransferase gene.

18 . (canceled)

19 . The composition of claim 17 , wherein the host cell line is a CHO cell line containing a knockdown of one or both the alleles of a Beta galactosidase gene.

20 . A composition comprising the population of Fc domain-containing binding proteins of claim 1 and a pharmaceutically acceptable carrier or excipient.

21 . A method of reducing a subject's anti-drug antibody (ADA) response to a first population of Fc domain-containing binding proteins, the method comprising glycoengineering the first population of Fc domain-containing binding proteins to obtain a binding protein composition comprising a second population of Fc-domain containing binding proteins having a G/M ratio of at least 10:1, a total percent amount of G1 and G2 glycoforms of more than 50%, and a total percent amount of M3-M9 glycoforms of less than 10%, wherein the second population of Fc domain-containing binding proteins has a greater serum half-life than the first population of Fc domain-containing binding proteins, wherein the Fc domain-containing binding proteins bind to tumor necrosis factor alpha (TNFα).

22 . The method of claim 21 , wherein the total percent amount of G1 and G2 glycoforms in the second population is more than 80%, or more than 99%.

23 . The method of claim 21 , wherein less than 5%, or less than 1%, or less than 0.1% of the Fc domain-containing binding proteins in the second population comprise M3-M9 glycoforms.

24 . The method of claim 21 , wherein the second population of Fc domain-containing binding proteins has a G1/2:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.

25 . The method of claim 21 , wherein the second population of Fc domain-containing binding proteins has a GS:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.

26 . The method of claim 21 , wherein the second population of Fc domain-containing binding proteins has a Gtotal:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.

27 .- 28 . (canceled)

29 . The method of claim 21 , wherein the first population of Fc domain-containing binding proteins comprises adalimumab or a variant thereof, wherein the variant of adalimumab is D2E7SS22 and comprises the heavy chain variable region sequence of SEQ ID NO:1 and the light chain variable region sequence of the light chain of SEQ ID NO:2.

30 .- 33 . (canceled)

34 . The method of claim 21 , wherein said glycoengineering comprises expressing the Fc-domain containing binding proteins in cultured mammalian host cell line that has been glycoengineered to produce hypergalactosylated and/or hypomannosylated binding proteins, wherein the host cell line is a CHO cell line containing a heterologous galactosyltransferase gene, wherein the host cell line is a CHO cell line containing a knockdown of one or both the alleles of a Beta galactosidase gene.

35 .- 37 . (canceled)

38 . A method of treating a disorder in a subject in need thereof, comprising administering to the subject an effective amount of the glycoengineered composition of any one of claim 1 , wherein the disorder is a TNFα associated disorder.

39 . (canceled)

Assignees

• Abbvie Inc

Inventors

• Labkovsky Boris
• Ghayur Tariq
• Gaza-Bulseco Georgeen
• Mishra Pratibha
• Hegde Subramanya
• Krishnan Sudha

Classifications

• C07K2317/77

  Internalization into the cell · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title