IP Library Granted Patent US 7,238,469
Granted Patent B2
US 7,238,469 · App. 10/177,930 · Granted Jul 3, 2007

Carbon monoxide improves outcomes in tissue and organ transplants and suppresses apoptosis

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Quick Facts
Patent No.
US 7,238,469
App. No.
10/177,930
Granted
Jul 3, 2007
Kind
B2
Abstract

The present invention features methods for transplanting organs, tissues and individual cells. Also featured are methods for maintaining cells in vitro and for enhancing survival and/or function of cells following transplantation. The methods include the administration of carbon monoxide in an amount sufficient to enhance cell survival and/or function.

Claims (57)

1. A method of transplanting an organ, the method comprising:

(a) administering to a donor by inhalation a gaseous pharmaceutical composition comprising carbon monoxide;

(b) obtaining from the donor an organ selected from the group consisting of: kidney, liver, heart, skin, small intestine, and pancreas; and

(c) transplanting the organ into a recipient, wherein the amount of carbon monoxide administered to the donor in step (a) is sufficient to enhance survival or function of the organ after transplantation into the recipient.

2. The method of claim 1 , wherein the pharmaceutical composition is administered to a live donor.

3. The method of claim 1 , wherein the pharmaceutical composition is administered to a brain-dead donor.

4. The method of claim 1 , wherein the pharmaceutical composition comprising carbon monoxide is administered to the donor prior to and following brain death.

5. The method of claim 1 , further comprising treating the organ in situ in the donor with a second pharmaceutical composition comprising carbon monoxide.

6. The method of claim 1 , further comprising treating the organ ex vivo, prior to the transplantation step, with a second pharmaceutical composition comprising carbon monoxide.

7. The method of claim 1 , further comprising the step of administering to the recipient by inhalation a second gaseous pharmaceutical composition comprising carbon monoxide before, during, or after step (c).

8. The method of claim 7 , wherein the second pharmaceutical composition is administered to the recipient before (c).

9. The method of claim 7 , wherein the pharmaceutical composition comprising carbon monoxide is administered to the recipient during (c).

10. The method of claim 7 , wherein the pharmaceutical composition comprising carbon monoxide is administered to the recipient after (c).

11. The method of claim 7 , wherein the pharmaceutical composition comprising carbon monoxide is administered to the recipient before and during (c).

12. The method of claim 7 , wherein the pharmaceutical composition comprising carbon monoxide is administered to the recipient before and after (c).

13. The method of claim 7 , wherein the pharmaceutical composition comprising carbon monoxide is administered to the recipient before, during, and after (c).

14. The method of claim 1 , wherein the organ is a liver.

15. The method of claim 1 , wherein the organ is a kidney.

16. The method of claim 1 , wherein the organ is a heart.

17. The method of claim 1 , wherein the organ is a pancreas.

18. The method of claim 1 , wherein the organ is a small intestine.

19. The method of claim 1 , wherein the organ is skin.

20. The method of claim 1 , wherein the donor is of a species different from that of the recipient.

21. The method of claim 1 , wherein the donor and the recipient are of the same species.

22. The method of claim 1 , wherein both the donor and the recipient are non-human animals.

23. The method of claim 1 , wherein both the donor and the recipient are humans.

24. The method of claim 1 , wherein the donor is a non-human animal and the recipient is a human.

25. The method of claim 1 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

26. The method of claim 1 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

27. The method of claim 1 , wherein the pharmaceutical composition is administered to the donor during (b).

28. The method of claim 2 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

29. The method of claim 2 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

30. The method of claim 2 , wherein the pharmaceutical composition is administered to the donor during (b).

31. The method of claim 5 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

32. The method of claim 5 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

33. The method of claim 5 , wherein the pharmaceutical composition is administered to the donor during (b).

34. The method of claim 14 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

35. The method of claim 14 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

36. The method of claim 14 , wherein the pharmaceutical composition is administered to the donor during (b).

37. The method of claim 15 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

38. The method of claim 15 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

39. The method of claim 15 , wherein the pharmaceutical composition is administered to the donor during (b).

40. The method of claim 16 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

41. The method of claim 16 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

42. The method of claim 16 , wherein the pharmaceutical composition is administered to the donor during (b).

43. The method of claim 17 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

44. The method of claim 17 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

45. The method of claim 17 , wherein the pharmaceutical composition is administered to the donor during (b).

46. The method of claim 18 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

47. The method of claim 18 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

48. The method of claim 18 , wherein the pharmaceutical composition is administered to the donor during (b).

49. The method of claim 21 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

50. The method of claim 21 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

51. The method of claim 21 , wherein the pharmaceutical composition is administered to the donor during (b).

52. The method of claim 23 , wherein, prior to step (a), the donor is identified as being suitable for donating an organ.

53. The method of claim 23 , wherein the pharmaceutical composition administered to the donor is supplied in the form of a pressurized gas in a vessel.

54. The method of claim 23 , wherein the pharmaceutical composition is administered to the donor during (b).

Assignments (23)
RELEASE OF SECURITY INTEREST Recorded Aug 14, 2025
From: ACQUIOM AGENCY SERVICES LLC
To: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; OCERA THERAPEUTICS LLC; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC
Reel/Frame 072324/0740 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 060434, FRAME 0536 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; VTESSE LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; SUCAMPO PHARMA AMERICAS LLC
Reel/Frame 065601/0347 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 049822, FRAME 0674 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: MALLINCKRODT INTERNATIONAL FINANCE S.A.; MALLINCKRODT CB LLC; MALLINCKRODT FINANCE GMBH; MALLINCKRODT US HOLDINGS LLC (F/K/A MALLINCKRODT US HOLDINGS INC.); MALLINCKRODT CARRIBEAN, INC.; MALLINCKRODT US POOL LLC; MNK 2011 LLC (F/K/A MALLINCKRODT INC.); LUDLOW LLC (F/K/A LUDLOW CORPORATION); CNS THERAPEUTICS, INC.; MALLINCKRODT ENTERPRISES HOLDINGS LLC (F/K/A MALLINCKRODT ENTERPRISES HOLDINGS, INC.); MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; LAFAYETTE PHARMACEUTICALS LLC; LIEBEL-FLARSHEIM COMPANY LLC; MALLINCKRODT BRAND PHARMACEUTICALS LLC (F/K/A MALLINCKRODT BRAND PHARMACEUTICALS, INC.); MALLINCKRODT VETERINARY, INC.; MALLINCKRODT US HOLDINGS LLC; IMC EXPLORATION COMPANY; MEH, INC.; MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC (F/K/A VTESSE INC.); MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING D.A.C.); INFACARE PHARMACEUTICAL CORPORATION; ST SHARED SERVICES LLC; THERAKOS, INC.; IKARIA THERAPEUTICS LLC; INO THERAPEUTICS LLC
Reel/Frame 065609/0454 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 035454, FRAME 0768 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: MALLINCKRODT INTERNATIONAL FINANCE S.A.; MALLINCKRODT CB LLC; MALLINCKRODT FINANCE GMBH; MALLINCKRODT US HOLDINGS LLC (F/K/A MALLINCKRODT US HOLDINGS INC.); MALLINCKRODT CARRIBEAN, INC.; MALLINCKRODT US POOL LLC; MNK 2011 LLC (F/K/A MALLINCKRODT INC.); LUDLOW LLC (F/K/A LUDLOW CORPORATION); CNS THERAPEUTICS, INC.; MALLINCKRODT ENTERPRISES HOLDINGS LLC (F/K/A MALLINCKRODT ENTERPRISES HOLDINGS, INC.); MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; LAFAYETTE PHARMACEUTICALS LLC; LIEBEL-FLARSHEIM COMPANY LLC; MALLINCKRODT BRAND PHARMACEUTICALS LLC (F/K/A MALLINCKRODT BRAND PHARMACEUTICALS, INC.); MALLINCKRODT VETERINARY, INC.; MALLINCKRODT US HOLDINGS LLC; IMC EXPLORATION COMPANY; MEH, INC.; MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC (F/K/A VTESSE INC.); MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING D.A.C.); INFACARE PHARMACEUTICAL CORPORATION; ST SHARED SERVICES LLC; THERAKOS, INC.; IKARIA THERAPEUTICS LLC; INO THERAPEUTICS LLC
Reel/Frame 065610/0035 →
RELEASE OF SECURITY INTERESTS IN PATENTS AT REEL 060389/FRAME 0913 Recorded Nov 15, 2023
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
To: OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); MALLINCKRODT LLC; MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
Reel/Frame 065583/0465 →
SECURITY INTEREST Recorded Nov 15, 2023
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; OCERA THERAPEUTICS LLC; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC
To: ACQUIOM AGENCY SERVICES LLC
Reel/Frame 065595/0376 →
NOTICE OF GRANT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Jun 22, 2022
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY
To: DEUTSCHE BANK AG NEW YORK BRANCH
Reel/Frame 060434/0536 →
SECURITY INTEREST Recorded Jun 17, 2022
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
Reel/Frame 060389/0913 →
RELEASE OF SECURITY INTEREST Recorded Jun 17, 2022
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
To: OCERA THERAPEUTICS, INC.; MALLINCKRODT LLC; MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING DESIGNATED ACTIVITY COMPANY); SPECGX LLC; STRATATECH CORPORATION; VTESSE LLC (F/K/A VTESSE INC.)
Reel/Frame 060389/0839 →
SECURITY INTEREST Recorded Dec 10, 2019
From: MALLINCKRODT ARD IP LIMITED; MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED; SPECGX LLC; OCERA THERAPEUTICS, INC.; MALLINCKRODT PHARMA IP TRADING DESIGNATED ACTIVITY COMPANY; STRATATECH CORPORATION; VTESSE INC.; MALLINCKRODT LLC
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
Reel/Frame 051256/0829 →
NOTICE OF GRANT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Jul 22, 2019
From: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 049822/0674 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT CRITICAL CARE FINANCE INC.
To: MALLINCKRODT PHARMA IP TRADING DAC
Reel/Frame 038038/0009 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT PHARMA IP TRADING DAC
To: MALLINCKRODT IP
Reel/Frame 038009/0058 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: MALLINCKRODT IP
To: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
Reel/Frame 038009/0016 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: INO THERAPEUTICS LLC
To: THERAKOS, INC.
Reel/Frame 038008/0956 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2016
From: THERAKOS, INC.
To: MALLINCKRODT CRITICAL CARE FINANCE INC.
Reel/Frame 038008/0824 →
SECURITY INTEREST Recorded Apr 19, 2015
From: INO THERAPEUTICS LLC
To: DEUTSCHE BANK AG NEW YORK BRANCH
Reel/Frame 035454/0768 →
RELEASE OF SECURITY INTEREST Recorded Apr 17, 2015
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH
To: INO THERAPEUTICS LLC
Reel/Frame 035453/0487 →
RELEASE OF SECURITY INTEREST Recorded Apr 17, 2015
From: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH
To: INO THERAPEUTICS LLC
Reel/Frame 035453/0513 →
PATENT SECURITY AGREEMENT (FIRST LIEN) Recorded Mar 11, 2014
From: INO THERAPEUTICS LLC
To: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS ADMINISTRATIVE AGENT
Reel/Frame 032426/0747 →
PATENT SECURITY AGREEMENT (SECOND LIEN) Recorded Mar 11, 2014
From: INO THERAPEUTICS LLC
To: CREDIT SUISSE AG, CAYMAN ISLANDS BRANCH, AS ADMINISTRATIVE AGENT
Reel/Frame 032426/0848 →
CHANGE OF NAME Recorded Jan 30, 2014
From: IKARIA HOLDINGS, INC.
To: IKARIA, INC.
Reel/Frame 032097/0626 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 30, 2014
From: IKARIA, INC.
To: INO THERAPEUTICS LLC
Reel/Frame 032097/0623 →