MIC therapy for specific immunosuppression in transplantation

Patent metadata

Field	Value
Publication number	US-11554139-B2
Application number	US-201917269027-A
Country	US
Kind code	B2
Filing date	May 17, 2019
Priority date	May 17, 2019
Publication date	Jan 17, 2023
Grant date	Jan 17, 2023

Abstract

The present invention relates to pharmaceutical compositions with isolated and treated whole blood cells or Peripheral Blood Mononuclear Cells (PBMCs) as well as such pharmaceutical compositions for use in the prevention and/or treatment of organ or cell graft rejection in a human graft recipient.

First claim

The invention claimed is:

1. A dosage of a pharmaceutical composition for a human graft recipient comprising:
a) isolated whole blood cells and/or Peripheral Blood Mononuclear Cells (PBMCs) treated with a therapeutically effective amount of mitomycin C,
wherein the isolated whole blood cells or PBMCs are obtained or derived from a human graft donor, and

b) optionally a pharmaceutically acceptable carrier;
wherein the dosage prevents or treats organ or cell graft rejection in the human graft recipient, and
wherein the dosage comprises at least 1×10 8 cells of the treated whole blood cells and/or the treated PBMCs.

2. The dosage according to claim 1 comprising Peripheral Blood Mononuclear Cells (PBMCs), wherein the PBMCs comprise monocytes and lymphocytes.

3. The dosage according to claim 1 comprising the pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is selected from of sugars; starches; cellulose and its derivates; powdered tragacanth; malt; gelatine; talc; cocoa butter; suppository waxes; oils; glycols; esters; agar; buffering agents; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; non-toxic, compatible lubricants; colouring agents; releasing agents; coating agents; sweetening, flavouring and perfuming agents; preservatives; and antioxidants.

4. A method for producing a dosage according to claim 1 comprising:
a) obtaining a blood cell sample from the human graft donor and optionally preparing Peripheral Blood Mononuclear Cells (PBMCs) from said blood cell sample,
b) treating the cells obtained in a) ex vivo with a therapeutically effective amount of mitomycin C, and
c) optionally, providing a pharmaceutically acceptable carrier and adding the carrier to the treated cells obtained in b).

5. The method according to claim 4 , wherein the total amount of the treated whole blood cells or the treated PBMCs in the dosage is at least 1.5×10 8 cells per kg body weight of the recipient.

6. The method according to claim 4 , wherein the pharmaceutically acceptable carrier is present and selected from sugars; starches; cellulose and its derivatives; powdered tragacanth; malt; gelatine; talc; cocoa butter; suppository waxes; oils; glycols; agar; buffering agents; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; non-toxic, compatible lubricants; colouring agents; releasing agents; coating agents; sweetening, flavouring, and perfuming agents; preservatives; and antioxidants.

7. A method for preventing and/or treating organ and/or cell graft rejection in a human graft recipient comprising administering to the recipient an amount of a pharmaceutical composition comprising:
a) isolated whole blood cells and/or Peripheral Blood Mononuclear Cells (PBMCs) treated with a therapeutically effective amount of mitomycin C,
wherein the isolated whole blood cells or PBMCs are obtained or derived from a human graft donor; and

b) optionally a pharmaceutically acceptable carrier;
wherein the amount of the pharmaceutical composition administered to the recipient comprises at least 1×10 8 cells of the treated whole blood cells and/or the treated PBMCs per kg body weight of the recipient;
wherein the pharmaceutical composition is administered to the recipient at least five days before an organ and/or cell transplantation.

8. The method according to claim 7 , comprising administering to the recipient at least 1.5×10 8 cells of the treated whole blood cells or the treated PBMCs per kg body weight of the recipient.

9. The method according to claim 7 , wherein the administration is performed as an intravenous, intramuscular, or subcutaneous injection, or as an infusion.

10. The method according to claim 7 comprising administering to the recipient at least 1.5×10 8 cells of the treated whole blood cells or the treated PBMCs per kg body weight of the recipient, wherein the administration is performed at least 7 days before the transplantation.

Assignees

• Tolerogenixx Gmbh
• Univ Heidelberg

Inventors

• Morath Christian
• Schmitt Anita
• Schaier Matthias
• Opelz Gerhard
• Terness Peter
• Kleist Christian
• Daniel Volker
• Süsal Caner
• Schmitt Michael
• Zeier Martin

Classifications

• A61P37/06 Primary

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

• A61K31/407 Primary

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/164

  of a carboxylic acid with an aminoalcohol, e.g. ceramides · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K31/422

  not condensed and containing further heterocyclic rings · CPC title