IP Library › Granted Patent US 12,269,855
Granted Patent B2
US 12,269,855 · App. 17/059,583 · Granted Apr 8, 2025

Interleukin-2 and use thereof

Inventors: Lishan Kang (Jiangsu, CN); Chunyin Gu (Jiangsu, CN); Fenggen Fu (Jiangsu, CN); Shuaixiang Zhou (Jiangsu, CN); Xinzhen Shi (Jiangsu, CN); Junjian Liu (Jiangsu, CN)
Assignee: INNOVENT BIOLOGICS (SUZHOU) CO., LTD.
C07K14/55A61K47/6843A61K47/6845A61K47/6853A61K47/6865A61K47/6871C07K16/18C07K16/248C07K16/3007C07K16/3053C07K16/40C12P21/02A61K38/00C07K2317/55C07K2317/56C07K2317/92C07K2319/30
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Quick Facts
Patent No.
US 12,269,855
App. No.
17/059,583
Granted
Apr 8, 2025
Kind
B2
Abstract

The present invention relates to a novel interleukin-2 (IL-2) mutant protein and use thereof. In particular, the present invention relates to an IL-2 mutant protein with reduced IL-2Rα receptor binding ability and/or increased IL-2Rβ receptor binding ability compared with the wild-type IL-2. The present invention further provides a fusion protein and an immunoconjugate comprising the IL-2 mutant protein, a nucleic acid encoding the IL-2 mutant protein, and a vector and a host cell comprising the nucleic acid. The present invention further provides a method for preparing the IL-2 mutant protein, a pharmaceutical composition comprising the IL-2 mutant protein, and therapeutic use of the mutant protein.

Claims (14)

1. An IL-2 mutant protein, comprising at least one mutation compared with a wild-type IL-2 comprising the amino acid sequence of SEQ ID NO:1, wherein the mutant protein has an eliminated or reduced binding affinity for an IL-2Rα receptor and/or an enhanced binding affinity for an IL-2Rß receptor, wherein the IL-2 mutant protein comprises mutations of K35/T37E/R38/F42 at positions corresponding to positions in SEQ ID NO: 1.

2. The IL-2 mutant protein of claim 1 , wherein the IL-2 mutant protein comprises a combinatorial mutation of

K35E/T37E/R38E/F42A

wherein the IL-2 mutant protein has a reduced or eliminated binding affinity for IL-2Rα receptor relative to wild IL-2 protein.

3. The IL-2 mutant protein of claim 1 , wherein the IL-2 mutant protein has an amino acid residue S at position 125.

4. The IL-2 mutant protein of claim 1 , wherein, when expressed in a fusion to an Fc antibody fragment in a mammalian cell, the IL-2 mutant protein reaches a purity of higher than 70%, 80%, or 90% after being purified by one-step protein A affinity chromatography, as detected by a SEC-HPLC.

5. A fusion protein comprising the IL2 mutant protein of claim 1 .

6. The fusion protein of claim 5 , wherein the IL-2 mutant protein is fused to an Fc antibody fragment.

7. An immunoconjugate comprising the IL-2 mutant protein of claim 1 and an antigen-binding molecule.

8. An isolated polynucleotide, encoding the IL-2 mutant protein of claim 1 or a fusion of the IL-2 mutant protein.

9. An expression vector, comprising the polynucleotide of claim 8 .

10. A host cell, comprising the polynucleotide of claim 8 .

11. A method for producing an IL-2 mutant protein or a fusion thereof, comprising culturing the host cell of claim 10 under a condition suitable for expressing the IL-2 mutant protein or the fusion thereof.

12. A pharmaceutical composition, comprising the IL-2 mutant protein of claim 1 or a fusion thereof, and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2020
From: KANG, LISHAN; GU, CHUNYIN; FU, FENGGEN; ZHOU, SHUAIXIANG; SHI, XINZHEN; LIU, JUNJIAN
To: INNOVENT BIOLOGICS (SUZHOU) CO., LTD.
Reel/Frame 054488/0303 →
Priority Claims (1)
CN 201811108649.X · Sep 21, 2018 · national
Continuity (1)
Related Publication 20210221863A1 · Jul 22, 2021
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