IP Library Granted Patent US 10,556,086
Granted Patent B2
US 10,556,086 · App. 13/827,240 · Granted Feb 11, 2020

Methods of administering high concentrations of nitric oxide

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Quick Facts
Patent No.
US 10,556,086
App. No.
13/827,240
Granted
Feb 11, 2020
Kind
B2
Abstract

Methods of administering therapeutic gases containing high concentrations of nitric oxide, particularly concentrations above 2,000 ppm. The therapeutic gas may be administered at a certain dosing rate, such as less than 166 micrograms of nitric oxide per second. Also, methods of administering a therapeutic gas containing nitric oxide to a patient, wherein a dose of nitric oxide is administered from a portable device that includes a delivery system and a mini-cylinder. Methods can also include intermittent administration of nitric oxide pulses.

Claims (51)

1. A method of treating pulmonary hypertension, the method comprising:

administering a plurality of pulses of therapeutic gas comprising nitric oxide (NO) to a patient in need thereof for a treatment time of at least 72 hours, wherein at least one pulse:

i. comprises a NO delivery concentration of greater than or equal to 4,600 ppm NO,

ii. is administered at a dosing rate of less than or equal to 83 μg NO per second,

iii. is administered at a therapeutic gas flow rate of less than or equal to 0.8 L/min,

iv. has a pulse volume of less than or equal to 1 mL, and

v. comprises less than 420 nmol of NO; and

diluting the pulses of therapeutic gas in the patient's trachea and/or lungs to an alveolar concentration less than the delivery concentration.

2. The method of claim 1 , wherein the delivery concentration is in a range from 4,600 ppm NO to 30,000 ppm NO.

3. The method of claim 1 , wherein the therapeutic gas is administered to the patient every breath.

4. The method of claim 1 , wherein the therapeutic gas is administered to the patient intermittently.

5. The method of claim 1 , wherein the pulmonary hypertension is pulmonary arterial hypertension (PAH).

6. The method of claim 1 , wherein the pulmonary hypertension is assosiated with chronic obstructive pulmonary disease (COPD).

7. The method of claim 1 , wherein the administration of the therapeutic gas provides less nasal irritation than administration of the therapeutic gas with a dosing rate above 83 μg NO per second and/or with more than 420 nmol NO per breath.

8. The method of claim 1 , wherein the plurality of pulses are administered to the patient at a dose in a range from 0.001 to 0.5 mg NO/kg/hr.

9. A method of reducing nasal irritation during nitric oxide administration, the method comprising:

administering a plurality of pulses of therapeutic gas comprising nitric oxide (NO) to a patient in need thereof for a treatment time of at least 72 hours, wherein at least one pulse:

i. comprises a NO delivery concentration of greater than or equal to 4,600 ppm NO,

ii. is administered at a dosing rate of less than or equal to 83 μg NO per second,

iii. is administered at a therapeutic gas flow rate of less than or equal to 0.8 L/min,

iv. has a pulse volume of less than or equal to 1 mL, and

v. comprises less than 420 nmol of NO; and

diluting the pulses of therapeutic gas in the patient's trachea and/or lungs to an alveolar concentration less than the delivery concentration.

10. The method of claim 9 , wherein the delivery concentration is in a range from 4,600 ppm NO to 30,000 ppm NO.

11. A method of delivering nitric oxide to a patient, the method comprising:

providing a therapeutic gas source comprising therapeutic gas having a nitric oxide (NO) concentration greater than or equal to 4,600 ppm NO;

introducing the therapeutic gas into a patient delivery tube having a control valve;

opening the control valve to provide a pulse of therapeutic gas;

delivering the pulse of therapeutic gas to the patient via a nasal cannula or breathing mask; and

diluting the pulse of therapeutic gas in the patient's trachea and/or lungs, wherein the pulse of therapeutic gas:

i. comprises a NO delivery concentration of greater than or equal to 4,600 ppm NO,

ii. is delivered at a dosing rate of less than or equal to 83 μg NO per second,

iii. is delivered at a therapeutic gas flow rate of less than or equal to 0.8 L/min,

iv. has a pulse volume of less than or equal to 1 mL, and

v. comprises less than 420 nmol of NO.

12. The method of claim 11 , wherein a plurality of pulses of the therapeutic gas is delivered to the patient.

13. The method of claim 12 , wherein each pulse of the plurality of pulses of the therapeutic gas:

i. comprises a NO delivery concentration of greater than or equal to 4,600 ppm NO,

ii. is delivered at a dosing rate of less than or equal to 83 μg per second,

iii. is delivered at a therapeutic gas flow rate of less than or equal to 0.8 L/min,

iv. has a pulse volume of less than or equal to 1 mL, and

v. comprises less than 420 nmol of NO.

14. The method of claim 12 , wherein the nitric oxide is delivered for treatment of pulmonary hypertension.

15. The method of claim 14 , wherein the pulmonary hypertension is pulmonary arterial hypertension (PAH).

16. The method of claim 14 , wherein the pulmonary hypertension is associated with chronic obstructive pulmonary disease (COPD).

17. The method of claim 12 , wherein the plurality of pulses is delivered for a treatment time of at least 72 hours.

18. The method of claim 17 , wherein the delivery of the therapeutic gas provides less nasal irritation than delivery of the therapeutic gas with a dosing rate above 83 μg NO per second and/or with more than 420 nmol NO per breath.

19. The method of claim 17 , wherein the therapeutic gas is delivered every breath.

20. The method of claim 17 , wherein the therapeutic gas is delivered intermittently.

21. The method of claim 12 , wherein the plurality of pulses are delivered to the patient at a dose in a range from 0.001 to 0.5 mg NO/kg/hr.

22. The method of claim 11 , wherein the delivery concentration is in a range from 4,600 ppm NO to 30,000 ppm NO.

Assignments (15)
SECURITY INTEREST Recorded Oct 28, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 073375/0395 →
CHANGE OF NAME Recorded Oct 10, 2025
From: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
To: MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY
Reel/Frame 073058/0559 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2025
From: MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY
To: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
Reel/Frame 073062/0558 →
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 →
SECURITY INTEREST Recorded Aug 1, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 072331/0001 →
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 →
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 →
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 →
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.)
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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 →