Granted Patent
B2
US 12,509,514 · App. 17/217,567 · Granted Dec 30, 2025
Antibodies comprising chimeric constant domains
Assignee:
Regeneron Pharmaceuticals, Inc.
C07K16/2809C07K16/2887C07K16/2896C07K16/46C12N15/85C07K2317/21C07K2317/24C07K2317/31C07K2317/52C07K2317/53C07K2317/71C07K2317/732C07K2317/734C07K2317/92C07K2317/94
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Abstract
Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.
Claims (32)
1 . An antibody comprising a first heavy chain, wherein the first heavy chain comprises a first heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 30, and a second heavy chain, wherein the second heavy chain comprises a second heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 37.
2 . The antibody of claim 1 , wherein the antibody binds to an FcγR with lower affinity than a corresponding antibody comprising a wild-type IgG1 heavy chain constant region, and the antibody binds FcγRIIA with higher affinity compared to the binding affinity of the antibody to FcγRIIB.
3 . The antibody of claim 1 , wherein the antibody is a bispecific antibody.
4 . The antibody of claim 3 , wherein the bispecific antibody comprises a common light chain.
5 . A composition comprising the antibody of claim 1 , and a pharmaceutically acceptable carrier or diluent.
6 . A composition comprising the bispecific antibody of claim 4 , and a pharmaceutically acceptable carrier or diluent.
7 . A nucleic acid molecule encoding the first heavy chain, the second heavy chain, or both the first heavy chain and the second heavy chain of the antibody of claim 1 .
8 . A vector comprising the nucleic acid molecule of claim 7 .
9 . An isolated host cell comprising the nucleic acid molecule of claim 7 .
10 . The isolated host cell of claim 9 , wherein the cell is a eukaryotic cell, an animal cell, a mammalian cell, a CHO cell or a CHO-K1 cell.
11 . An isolated host cell comprising a first nucleic acid molecule encoding a first immunoglobulin (Ig) heavy chain, a second nucleic acid molecule encoding a second Ig heavy chain, and a third nucleic acid molecule encoding an Ig light chain, wherein the first Ig heavy chain comprises a first heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 30, and wherein the second Ig heavy chain comprises a second heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 37.
12 . The isolated host cell of claim 11 , wherein the first Ig heavy chain further comprises a first heavy chain variable region, wherein the second Ig heavy chain further comprises a second heavy chain variable region, and wherein the Ig light chain comprises a light chain variable region and a light chain constant region.
13 . The isolated host cell of claim 11 , wherein the cell is a eukaryotic cell, an animal cell, a mammalian cell, a CHO cell or a CHO-K1 cell.
14 . A method of making an antibody, the method comprising culturing the isolated host cell of claim 12 , wherein the antibody is secreted into a cell culture medium.
15 . The method of claim 14 , further comprising isolating the antibody from the cell culture medium.
16 . The method of claim 15 , further comprising formulating the antibody isolated from the cell culture medium with a pharmaceutically acceptable carrier or diluent.
17 . An antibody comprising a first heavy chain, wherein the first heavy chain comprises a first heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 31, and a second heavy chain, wherein the second heavy chain comprises a second heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 38.
18 . The antibody of claim 17 , wherein the antibody binds to an FcγR with lower affinity than a corresponding antibody comprising a wild-type IgG4 heavy chain constant region, and the antibody binds FcγRIIA with higher affinity compared to the binding affinity of the antibody to FcγRIIB.
19 . The antibody of claim 17 , wherein the antibody is a bispecific antibody.
20 . The antibody of claim 19 , wherein the bispecific antibody comprises a common light chain.
21 . A composition comprising the antibody of claim 17 , and a pharmaceutically acceptable carrier or diluent.
22 . A composition comprising the bispecific antibody of claim 20 , and a pharmaceutically acceptable carrier or diluent.
23 . A nucleic acid molecule encoding the first heavy chain, the second heavy chain, or both the first heavy chain and the second heavy chain of the antibody of claim 17 .
24 . A vector comprising the nucleic acid molecule of claim 23 .
25 . An isolated host cell comprising the nucleic acid molecule of claim 23 .
26 . The isolated host cell of claim 25 , wherein the cell is a eukaryotic cell, an animal cell, a mammalian cell, a CHO cell, or a CHO-K1 cell.
27 . An isolated host cell comprising a first nucleic acid molecule encoding a first immunoglobulin (Ig) heavy chain, a second nucleic acid molecule encoding a second Ig heavy chain, and a third nucleic acid molecule encoding an Ig light chain, wherein the first Ig heavy chain comprises a first heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 31, and the second Ig heavy chain comprises a second heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 38.
28 . The isolated host cell of claim 27 , wherein the first Ig heavy chain further comprises a first heavy chain variable region, the second Ig heavy chain further comprises a second heavy chain variable region, and the Ig light chain comprises a light chain variable region and a light chain constant region.
29 . The isolated host cell of claim 27 , wherein the cell is a eukaryotic cell, an animal cell, a mammalian cell, a CHO cell or a CHO-K1 cell.
30 . A method of making an antibody, the method comprising culturing the isolated host cell of claim 28 , wherein the antibody is secreted into a cell culture medium.
31 . The method of claim 30 , further comprising isolating the antibody from the cell culture medium.
32 . The method of claim 31 , further comprising formulating the antibody isolated from the cell culture medium with a pharmaceutically acceptable carrier or diluent.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 7, 2024
From: DAVIS, SAMUEL; SMITH, ERIC; PATEL, SUPRIYA
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 067659/0845 →
Continuity (5)
Provisional Application
61759578
· Feb 1, 2013
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