TGF-beta receptor fusion protein pharmaceutical composition and use thereof

Patent metadata

Field	Value
Publication number	US-12559539-B2
Application number	US-201917290707-A
Country	US
Kind code	B2
Filing date	Nov 8, 2019
Priority date	Nov 9, 2018
Publication date	Feb 24, 2026
Grant date	Feb 24, 2026

Abstract

Disclosed in the present disclosure are a TGF-β receptor fusion protein pharmaceutical composition and a use thereof. Specifically, the pharmaceutical composition comprises a TGF-β receptor fusion protein in a sodium citrate buffer, and the TGF-β receptor fusion protein comprises a PD-L1 antibody targeting portion and a TGF-βRII extracellular region. In addition, the pharmaceutical composition may also comprise a sugar and a non-ionic surfactant.

First claim

What is claimed is:

1 . A pharmaceutical composition comprising:
about 0.5 mg/ml to about 100 mg/ml of a TGF-β receptor fusion protein; about 5 mM to about 20 mM of a citric acid-sodium citrate buffer; about 60 mg/ml to about 90 mg/ml of sucrose; and about 0.4 mg/ml to about 0.8 mg/ml of polysorbate 80; wherein the pH of the pharmaceutical composition is about 6.0 to about 6.5; and wherein the TGF-β receptor fusion protein consists of: a fusion peptide formed by a heavy chain of a PD-L1 antibody and TGF-βRII extracellular domain (TGF-βRII ECD), the sequence of which is set forth in SEQ ID NO: 23 or has at least 85% identity to the sequence set forth in SEQ ID NO: 23, and a light chain of the PD-L1 antibody, the sequence of which is set forth in SEQ ID NO: 13 or has at least 85% identity to the sequence set forth in SEQ ID NO: 13.

2 . The pharmaceutical composition according to claim 1 , wherein the concentration of the citric acid-sodium citrate buffer is about 10 mM.

3 . The pharmaceutical composition according to claim 1 , wherein the concentration of the TGF-β receptor fusion protein is about 30 mg/ml to about 70 mg/ml.

4 . The pharmaceutical composition according to claim 1 , wherein the pH of the pharmaceutical composition is about 6.2.

5 . The pharmaceutical composition according to claim 1 , wherein the concentration of the sucrose is about 80 mg/ml.

6 . The pharmaceutical composition according to claim 1 , wherein the concentration of the polysorbate 80 is about 0.4 mg/ml.

7 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises:
about 30 mg/ml to about 70 mg/ml of the TGF-β receptor fusion protein, about 5 mM to about 20 mM of the citric acid-sodium citrate buffer, about 60 mg/ml to about 90 mg/ml of sucrose, and about 0.4 mg/ml to about 0.8 mg/ml of polysorbate 80;
and the pH of the pharmaceutical composition is about 6.0 to about 6.5.

8 . The pharmaceutical composition according to claim 1 , wherein the concentration of the TGF-β receptor fusion protein is about 50 mg/ml.

9 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises:
about 50 mg/ml of the TGF-β receptor fusion protein, about 10 mM of the citric acid-sodium citrate buffer, about 80 mg/ml of sucrose, and about 0.4 mg/ml of polysorbate 80; and wherein the pH of the pharmaceutical composition is about 6.2.

10 . A lyophilized preparation comprising a TGF-β receptor fusion protein, which is obtained by lyophilizing the pharmaceutical composition according to claim 1 .

11 . A reconstituted solution comprising a TGF-β receptor fusion protein, which is obtained by reconstituting the lyophilized preparation of claim 10 .

12 . A lyophilized preparation comprising a TGF-β receptor fusion protein, which can be reconstituted to form the pharmaceutical composition according to claim 1 .

13 . An article of manufacture, comprising one or more container(s), the one or more container comprising: the pharmaceutical composition according to claim 1 .

14 . A method for preparing the pharmaceutical composition of claim 1 , the method comprises: a step of contacting the TGF-β receptor fusion protein with the buffer.

Assignees

• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Tian Chenmin
• Li Hao
• Liu Xun

Classifications

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title