UTI fusion proteins

Patent metadata

Field	Value
Publication number	US-10351618-B2
Application number	US-201715823398-A
Country	US
Kind code	B2
Filing date	Nov 27, 2017
Priority date	Feb 24, 2014
Publication date	Jul 16, 2019
Grant date	Jul 16, 2019

Abstract

The present invention provides UTI fusion proteins, DNA sequences for producing the same, and pharmaceutical compositions and methods of using the same.

First claim

What is claimed is:

1. An isolated urinary trypsin inhibitor (UTI) fusion protein comprising amino acids 1 to 149 of SEQ ID NO:1 linked to a wild-type Fc domain, wherein the Fc domain excludes the first constant region immunoglobulin domain, or fragment thereof that does not contain one or more substitutions.

2. A dimer comprising two isolated urinary trypsin inhibitor (UTI) fusion proteins of claim 1 , wherein the Fc domains, or fragments thereof, are associated covalently.

3. The isolated UTI fusion protein of claim 1 or the dimer of claim 2 wherein the Fc domain is selected from the group consisting of an IgG1, an IgG2 and an IgG4 Fc domain.

4. The isolated UTI fusion protein of claim 1 or the dimer of claim 2 , wherein the Fc domain is an IgG1 Fc domain.

5. A pharmaceutical composition comprising the UTI fusion protein of claim 1 or the dimer of claim 2 , and a pharmaceutically acceptable excipient.

6. A nucleic acid encoding the UTI fusion protein of claim 1 or the dimer of claim 2 .

7. An expression vector comprising the nucleic acid of claim 6 .

8. A recombinant host cell comprising the expression vector of claim 7 .

9. The recombinant host cell of claim 8 , wherein the cell is selected from the group consisting of a mammalian cell, an insect cell, an E. coli cell, a yeast cell, and a plant cell.

10. The recombinant host cell of claim 9 , wherein the mammalian cell is selected from the group consisting of a Chinese hamster ovary (CHO) cell, an HEK 293 cell, an NSO cell, a HeLa cell, a baby hamster kidney (BHK) cell, a monkey kidney cell (COS) and a human hepatocellular carcinoma cell.

11. A method of treating a UTI-related condition comprising administering to a patient in need thereof an effective amount of the UTI fusion protein of claim 1 or the dimer of claim 2 .

12. The method of claim 11 , wherein the UTI-related condition is selected from the group consisting of pancreatitis, arthritis, SARS, systemic inflammatory response syndrome, acute circulatory failure, sepsis, hepatitis, appendicitis, colitis, organ failure, organ damage, reperfusion injury, Stevens-Johnson syndrome, toxic epidermal necrolysis, shock, ischemic injuries, acute lung injury, asthma, lung inflammation, pneumonia, disseminated intravascular coagulation, and acute respiratory distress syndrome.

13. The method of claim 11 , wherein the UTI-related condition is acute pancreatitis.

14. The method of claim 11 , wherein the UTI-related condition is selected from the group consisting of endoscopy induced pancreatitis, pancreas damage, kidney damage, lung damage, lung injury caused by acute aortic dissection, and ventilator associated pneumonia.

15. A method of producing a urinary trypsin inhibitor (UTI) fusion protein, comprising placing the recombinant host cell of claim 8 in a growth medium such that a recombinant fusion protein is expressed, and isolating the recombinant fusion protein from the cell or growth medium.

16. A method of producing a UTI fusion protein, wherein the UTI fusion protein of claim 1 or the dimer of claim 2 is produced in a transgenic animal.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Chamberlain Aaron
• Liu Qiang
• Schmidt Mathias

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/08

  Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04) · CPC title