IP Library Granted Patent US 11,567,080
Granted Patent B2
US 11,567,080 · App. 16/066,111 · Granted Jan 31, 2023

Diagnostic agent and medicine comprising ADAMTS13 as main ingredient

Inventors: Koichiro Hata (Kyoto, JP); Shinji Uemoto (Kyoto, JP); Hirofumi Hirao (Kyoto, JP); Toyonari Kubota (Kyoto, JP)
Assignees: KYOTO UNIVERSITY; KM BIOLOGICS CO., LTD.
G01N33/573A61K38/4886G01N33/576G01N2333/96494G01N2800/08G01N2800/085
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Quick Facts
Patent No.
US 11,567,080
App. No.
16/066,111
Granted
Jan 31, 2023
Kind
B2
Abstract

New use of ADAMTS13 in the clinical filed is provided. The use of ADAMTS13 as a biomarker for monitoring the onset of liver damage, hepatic ischemia/reperfusion injury or the liver function after liver transplantation: a method of testing liver damage, a method of testing hepatic ischemia/reperfusion injury, or a method of testing the liver function after liver transplantation, each of the methods comprising measuring or monitoring the ADAMTS13 activity in a sample from a mammal; an agent for treating diseases selected from the group consisting of liver damage, hepatic ischemia/reperfusion injury and hepatic dysfunction after liver transplantation, which comprises ADAMTS13 or a mutant of ADAMTS13 as an effective ingredient.

Claims (14)

1. A method of testing and treating a disorder of hepatic non-parenchymal cells, comprising:

measuring or monitoring the ADAMTS13 activity in a sample from a mammal, wherein the disorder of hepatic non-parenchymal cells is a disorder after chemotherapy of colorectal cancer, and wherein the mammal is diagnosed with the disorder of hepatic non-parenchymal cells when a decrease in the ADAMTS13 activity in the sample is observed as compared to the ADAMTS13 activity in a sample from a healthy subject, and

treating the mammal diagnosed with the disorder of hepatic non-parenchymal cells by administering ADAMTS13 or a mutant of ADAMTS13 having ADAMTS13 activity as an effective ingredient, or a pharmaceutical composition comprising ADAMTS13 or a mutant of ADAMTS13 having ADAMTS13 activity as an effective ingredient.

2. The method of claim 1 , wherein the mammal is human.

3. The method of claim 1 , wherein the sample from a mammal is blood from a mammal.

4. The method of claim 1 , wherein the mutant of ADAMTS13 is a molecule comprising a minimum unit necessary for exerting ADAMTS13 activity, wherein the minimum unit consists of a portion of ADAMTS13 from the metalloprotease domain to a spacer domain.

5. The method of claim 4 , wherein the mutant of ADAMTS13 is a C-terminus deficient mutant W688X (ADAMTS13W688X protein) which is a resultant of deletion of the C-terminal portion from the amino acid at position 689 from ADAMTS13 consisting of 1427 amino acid residues.

6. The method of claim 1 , wherein the administration of ADAMTS13 or the mutant of ADAMTS13 is systemic administration or topical administration.

7. The method of claim 6 , wherein systemic administration is selected from the group consisting of oral, subdermal, intramuscular, intraperitoneal, subcutaneous, nasal, sublingual and rectal administration.

8. The method of claim 1 , wherein the pharmaceutical composition is administered orally and is selected from the group consisting of tablets, capsules, powders, and liquids.

9. The method of claim 8 , wherein the tablets comprise ADAMTS13 or a mutant of ADAMTS13 having ADAMTS13 activity, and gelatin or adjuvants.

10. The method of claim 8 , wherein the liquids comprise ADAMTS13 or a mutant of ADAMTS13 having ADAMTS13 activity, and a liquid carrier selected from the group consisting of water, petroleum, animal oils, vegetable oils, mineral oils, synthetic oils, saline, a solution of glucose, a solution of ethylene glycol, a solution of propylene glycol, and a solution of polyethylene glycol.

11. The method of claim 1 , wherein the pharmaceutical composition is administered by intravenous, cutaneous, or subcutaneous injection, and the pharmaceutical composition comprises ADAMTS13 or a mutant of ADAMTS13 having ADAMTS13 activity, and a solution comprising at least one additional component selected from the group consisting of isotonic media, a preservative, a stabilizing agent, a buffer, an antioxidant and other pharmaceutically acceptable additives.

12. The method of claim 1 , wherein the pharmaceutical composition is administered in an amount of 100 to 700 units/kg body weight by intravenous injection, intramuscular injection, or subcutaneous injection, and is administered one or more times.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 15, 2020
From: THE CHEMO-SERO-THERAPEUTIC RESEARCH INSTITUTE
To: KM BIOLOGICS CO., LTD.
Reel/Frame 051520/0971 →
CHANGE OF ADDRESS OF ASSIGNEE Recorded Apr 15, 2019
From: THE CHEMO-SERO-THERAPEUTIC RESEARCH INSTITUTE
To: THE CHEMO-SERO-THERAPEUTIC RESEARCH INSTITUTE
Reel/Frame 050169/0778 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 26, 2018
From: HATA, KOICHIRO; UEMOTO, SHINJI; HIRAO, HIROFUMI; KUBOTA, TOYONARI
To: KYOTO UNIVERSITY; THE CHEMO-SERO-THERAPEUTIC RESEARCH INSTITUTE
Reel/Frame 046202/0558 →
Cited By (2)
US 12,661,390 US 12,698,494