IP Library › Granted Patent US 12,649,798
Granted Patent B2
US 12,649,798 · App. 16/963,701 · Granted Jun 9, 2026

Polypeptide variants and uses thereof

Inventors: Simone Oostindie (Utrecht, NL); Andreas Hollenstein (Utrecht, NL); Frank Beurskens (Utrecht, NL); Kristin Strumane (Werkhoven, NL); Janine Schuurman (Diemen, NL); Rob De Jong (Utrecht, NL)
Assignee: GENMAB B.V.
C07K16/2893A61P35/00C07K16/2887C07K16/2896C07K2317/24C07K2317/31C07K2317/72C07K2317/734
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Quick Facts
Patent No.
US 12,649,798
App. No.
16/963,701
Granted
Jun 9, 2026
Kind
B2
Abstract

The present invention relates to combination therapy involving two or more Fc region-containing antigen-binding polypeptides, such as antibodies, wherein the polypeptides have been modified such that hetero-oligomerization between the polypeptides is strongly favored over homo-oligomerization when the polypeptides are bound to their corresponding target antigens. The invention also relates to polypeptides, compositions, kits and devices suitable for use in the combination therapy of the invention.

Claims (34)

1 . A polypeptide comprising a Fc region of a human IgG and an antigen-binding region capable of binding to an antigen, wherein said polypeptide comprises a Y436N, Y436K, Y436Q or Y436R mutation of an amino acid position corresponding to Y436 in human IgG1, and a K439F, K439I, K439Y, K439T, K439V, K439W, or K439E mutation of an amino acid position corresponding to K439 in human IgG1.

2 . A polypeptide comprising a Fc region of a human IgG and an antigen-binding region capable of binding to an antigen, wherein said polypeptide comprises a Q438R, Q438H, Q438G or Q438N mutation of an amino acid position corresponding to Q438 in human IgG1, and an S440K mutation of an amino acid position corresponding to S440 in human IgG1.

3 . The polypeptide according to claim 1 , wherein said polypeptide further comprises an E430G mutation of an amino acid position corresponding to E430 in human IgG1.

4 . The polypeptide according to claim 2 , wherein said polypeptide further comprises an E430G mutation of an amino acid position corresponding to E430 in human IgG1.

5 . The polypeptide according to claim 1 , wherein said polypeptide is an antibody.

6 . The polypeptide according to claim 1 , wherein said polypeptide is an IgG1 antibody.

7 . The polypeptide according to claim 5 , wherein said antibody is human, humanized or chimeric.

8 . The polypeptide according to claim 5 , wherein said antibody is bispecific.

9 . The polypeptide according to claim 1 , wherein said antigen is a cell surface-exposed molecule.

10 . The polypeptide according to claim 1 , wherein said antigen is not a death receptor.

11 . A pharmaceutical composition comprising the polypeptide as defined in claim 1 and a pharmaceutically-acceptable carrier.

12 . The polypeptide according to claim 1 , wherein said polypeptide is a full-length antibody.

13 . The polypeptide according to claim 2 , wherein said polypeptide is an antibody.

14 . The polypeptide according to claim 2 , wherein said polypeptide is a full-length antibody.

15 . The polypeptide according to claim 2 , wherein said polypeptide is an IgG1 antibody.

16 . The polypeptide according to claim 14 , wherein said antibody is human, humanized or chimeric.

17 . The polypeptide according to claim 14 , wherein said antibody is bispecific.

18 . A pharmaceutical composition comprising the polypeptide as defined in claim 2 and a pharmaceutically-acceptable carrier.

19 . A mixture of antibodies comprising:

(a) a first antibody comprising an Fc region of a human IgG, wherein the Fc region comprises a Y436N, Y436K, Y436Q or Y436R mutation of an amino acid position corresponding to Y436 in human IgG1, and a K439F, K439I, K439Y, K439T, K439V, K439W, or K439E mutation of an amino acid position corresponding to K439 in human IgG1, and

(b) a second antibody comprising an Fc region of a human IgG, wherein the Fc region comprises a Q438R, Q438K, Q438H, Q438G or Q438N mutation of an amino acid position corresponding to Q438 in human IgG1, and an S440K mutation of an amino acid position corresponding to S440 in human IgG1.

20 . The mixture of antibodies according to claim 19 , wherein the Fc regions of the first and second antibodies further comprise an E430G mutation of an amino acid position corresponding to E430 in human IgG1.

21 . The mixture of antibodies according to claim 19 , wherein:

(a) the Fc region of the first antibody comprises a Y436N mutation and a K439E mutation of amino acid positions corresponding to Y436 and K439 in human IgG1, respectively, and

(b) the Fc region of the second antibody comprises a Q438R mutation and a S440K mutation of amino acid positions corresponding to Q438 and S440 in human IgG1, respectively.

22 . The mixture of antibodies according to claim 21 , wherein the Fc regions of the first and second antibodies further comprise an E430G mutation of an amino acid position corresponding to E430 in human IgG1.

23 . The mixture of antibodies according to claim 19 , wherein:

(a) the Fc region of the first antibody comprises Y436N, K439E, and E430G mutations of amino acid positions corresponding to Y436, K439, and E430 in human IgG1, respectively, and

(b) the Fc region of the second antibody comprises Q438R, S440K, and E430G mutations of amino acid positions corresponding to Q438, S440, and E430 in human IgG1, respectively.

24 . The mixture of antibodies according to claim 23 , wherein the first antibody and/or second antibody is an IgG1 antibody.

25 . The mixture of antibodies according to claim 23 , wherein the first antibody and/or second antibody is human, humanized, or chimeric.

26 . A pharmaceutical composition comprising the mixture of antibodies according to claim 23 and a pharmaceutically-acceptable carrier.

27 . A kit comprising a first container comprising a first antibody and a second container comprising a second antibody, wherein both the first and second antibodies are as defined in claim 23 .

28 . A dual chamber syringe comprising a first compartment comprising a first antibody and a second compartment comprising a second antibody, wherein the first and second antibodies are as defined in claim 23 .

Assignments (3)
SECURITY INTEREST Recorded Dec 15, 2025
From: GENMAB A/S; GENMAB B.V.; GENMAB HOLDING B.V.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 073933/0597 →
NOTICE OF GRANT OF SECURITY INTEREST IN PATENTS Recorded Dec 15, 2025
From: GENMAB HOLDING B.V.; GENMAB A/S; GENMAB B.V.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 073949/0722 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2021
From: OOSTINDIE, SIMONE; HOLLENSTEIN, ANDREAS; BEURSKENS, FRANK; STRUMANE, KRISTIN; SCHUURMAN, JANINE; DE JONG, ROB
To: GENMAB B.V.
Reel/Frame 056317/0665 →
Priority Claims (1)
DK 2018 00041 · Jan 24, 2018 · national
Continuity (1)
Related Publication 20210107988A1 · Apr 15, 2021
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