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Methods for mitigating liver injury and promoting liver hypertrophy, regeneration and cell engraftment in conjunction with radiation and/or radiomimetic treatments

A technology of radiation therapy and mimics, applied in the field of reducing liver damage and promoting liver hypertrophy, regeneration and cell implantation combined with radiation and/or radiation mimic therapy

Pending Publication Date: 2021-12-07
JANSSEN PHARMA NV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] There are no clinically approved drugs to promote engraftment of hepatocytes, such as hepatic sinusoidal endothelial cells, stem cells, hepatocyte progenitors, or hepatocytes in the liver
Additionally, there are no drugs approved to enhance hepatic hypertrophy

Method used

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  • Methods for mitigating liver injury and promoting liver hypertrophy, regeneration and cell engraftment in conjunction with radiation and/or radiomimetic treatments
  • Methods for mitigating liver injury and promoting liver hypertrophy, regeneration and cell engraftment in conjunction with radiation and/or radiomimetic treatments
  • Methods for mitigating liver injury and promoting liver hypertrophy, regeneration and cell engraftment in conjunction with radiation and/or radiomimetic treatments

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0130] Embodiment 1 is a method of alleviating radiation-induced liver disease (RILD) in a subject in need thereof, the method comprising administering to the subject an effective amount of a thrombopoietin (TPO) mimetic, wherein Administering to the subject an effective amount of the TPO mimetic reduces radiation-induced liver disease in the subject.

[0131] Embodiment 1(a) is the method of embodiment 1, wherein the TPO mimetic comprises a peptide having the amino acid sequence of SEQ ID NO:1.

[0132] Embodiment 1(b) is the method of embodiment 1(a), wherein the peptide has the amino acid sequence of SEQ ID NO:2.

[0133] Embodiment 1(c) is the method of Embodiment 1(a) or 1(b), wherein the TPO mimetic further comprises a hydrophilic polymer covalently linked to the peptide.

[0134] Embodiment 1(d) is the method of Embodiment 1(c), wherein the hydrophilic polymer is any of: i) polyethylene glycol (PEG), ii) polypropylene glycol, iii) polylactic acid, or iv) Polyglycolic ...

Embodiment approach 2

[0145] Embodiment 2 is the method of any one of embodiments 1-1(m)(1), wherein the radiation-induced liver disease is any one or more of the following: hepatomegaly, hepatic necrosis, apoptosis Death, ascites, elevated liver enzymes, thrombocytopenia, sinusoidal obstruction syndrome (SOS) and central veno-occlusive disease (VOD).

[0146] Embodiment 2(a) is the method of Embodiment 2, wherein the radiation-induced liver disease is hepatomegaly.

[0147] Embodiment 2(b) is the method of Embodiment 2, wherein the radiation-induced liver disease is ascites.

[0148] Embodiment 2(c) is the method of Embodiment 2, wherein the radiation-induced liver disease is elevated liver enzymes.

[0149] Embodiment 2(d) is the method of Embodiment 2, wherein the radiation-induced liver disease is thrombocytopenia.

[0150] Embodiment 2(e) is the method of Embodiment 2, wherein the radiation-induced liver disease is sinusoidal obstruction syndrome (SOS).

[0151] Embodiment 2(f) is the metho...

Embodiment approach 3

[0157] Embodiment 3(c) is the method of Embodiment 3(a) or 1(b), wherein the TPO mimetic further comprises a hydrophilic polymer covalently linked to the peptide.

[0158] Embodiment 3(d) is the method of Embodiment 3(c), wherein the hydrophilic polymer is any of: i) polyethylene glycol (PEG), ii) polypropylene glycol, iii) polylactic acid, or iv) Polyglycolic acid.

[0159] Embodiment 3(e) is the method of Embodiment 3(d), wherein the hydrophilic polymer is PEG.

[0160] Embodiment 3(f) is the method of embodiment 3(e), wherein the PEG is monomethoxypolyethylene glycol (MePEG-OH), monomethoxypolyethylene glycol-succinate (MePEG-OH), S), monomethoxypolyethylene glycol-succinimidyl succinate (MePEG-S-NHS), monomethoxypolyethylene glycol-amine (MePEG-NH2), monomethoxypolyethylene glycol Either of diol-trifluoroethanesulfonate (MePEG-TRES) or monomethoxypolyethylene glycol-imidazolyl-carbonyl (MePEG-IM).

[0161] Embodiment 3(g) is the method of Embodiment 3(e), wherein the PE...

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Abstract

Methods and kits for mitigating liver injury and promoting liver regeneration and engraftment in a subject treated with a targeted radiation therapy are described. In particular, an effective amount of a thrombopoietin mimetic, such as RWJ-800088 or romiplostim, is used to mitigate the radiation-induced liver diseases and promote beneficial effects for liver regeneration and engraftment in conjunction with radiation or radiomimetics.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Patent Application No. 62 / 796,806, filed January 25, 2019, the disclosure of which is incorporated herein by reference in its entirety. [0003] References to Sequence Listings Submitted Electronically [0004] This application contains a sequence listing, which is electronically submitted via EFS-Web as a sequence listing in ASCII format, with the file name "Sequence Listing of 688097.0956 / 456WO", date of creation January 23, 2020, and a size of approximately 3.6kb. The sequence listing submitted via EFS-Web is part of this specification and is hereby incorporated by reference in its entirety. technical field [0005] The present invention relates to methods and kits for reducing liver injury and promoting liver regeneration, hypertrophy and hepatocyte engraftment in a subject in need thereof. In particular, the invention relates to methods comprising administering to a s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/19A61K38/17A61K38/18A61K35/407A61K38/48A61K35/44A61P1/16A61P35/04
CPCA61K38/196A61K35/407A61K35/44A61K38/195A61K38/1866A61K38/1825A61K38/1808A61K38/193A61K38/18A61K38/1709A61K38/48C12Y304/24007A61P1/16A61K2300/00A61K9/0019A61K45/06A61N5/1049A61P1/00A61P35/04A61K38/1833A61K38/4886
Inventor G·艾肯鲍姆C·古哈
Owner JANSSEN PHARMA NV
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