IP Library Granted Patent US 10,613,103
Granted Patent B2
US 10,613,103 · App. 15/320,635 · Granted Apr 7, 2020

Methods of identifying and treating premature infants at risk for BPD

Inventors: Douglas Stuart Greene (Newtown, PA); Joseph J. Medicis (Syracuse, NY); Jim Potenziano (Binghamton, NY)
Assignee: Mallinckrodt Hospital Products IP Limited
G01N33/84A61K9/007A61K33/00C12Q1/6883G01N33/497C12Q2600/106C12Q2600/156G01N2800/12
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Quick Facts
Patent No.
US 10,613,103
App. No.
15/320,635
Granted
Apr 7, 2020
Kind
B2
Abstract

Methods for identifying premature infants at risk for developing bronchopulmonary dysplasia and/or most likely to benefit from administration of inhaled nitric oxide for prevention of bronchopulmonary dysplasia (BPD). Methods for treating premature infants identified as at risk and/or likely to benefit are provided. also provided are methods for identifying premature infants that are not at risk for developing bronchopulmonary dysplasia and/or unlikely to benefit from administration of inhaled nitric oxide for prevention of bronchopulmonary dysplasia, and methods for avoiding risks of toxicity and undesirable side effects associated with inhaled nitric oxide therapy comprising administering only non-iNO treatment modalities to these infants.

Claims (19)

1. A method for reducing the likelihood of a premature infant of developing bronchopulmonary dysplasia comprising:

a) obtaining a plasma sample from the infant prior to initiation of inhaled nitric oxide therapy;

b) measuring a total concentration of nitrite and nitrate in the plasma sample;

c) determining whether the measured concentration of nitrite and nitrate is less than about 50 μM, wherein a concentration of less than about 50 μM indicates that the infant is likely to have a therapeutic response to inhaled nitric oxide; and

d) treating the infant with inhaled nitric oxide to reduce the likelihood of development of bronchopulmonary dysplasia when the measured concentration of nitrite and nitrate is less than about 50 μM,

wherein the premature infant is less than 30 weeks gestational age.

2. The method of claim 1 , wherein the measured concentration of nitrite and nitrate is about 0-45 μM, about 5-40 μM, about 10-30 μM, about 20 μM, or below the detection limit of an assay used to measure the concentration.

3. A method of reducing the likelihood of a premature infant of developing bronchopulmonary dysplasia comprising:

a) testing the infant for one or more of

(i) a plasma total concentration of nitrate and nitrite;

(ii) a concentration of nitric oxide in exhaled ambient or nitric oxide-free air; and

(iii) presence of a genetic mutation in a gene encoding nitric oxide synthase that results in decrease endogenous synthesis of nitric oxide;

b) determining whether the total concentration of nitrate and nitrite in the plasma is less than about 50 μM, whether the concentration of nitric oxide in the exhaled air is less than about 1.5 ppb and/or whether the genetic mutation is present or absent; and

c) treating the infant with inhaled nitric oxide to reduce the likelihood of development of bronchopulmonary dysplasia if the total concentration of nitrate and nitrite in the plasma is less than about 50 μM, the concentration of nitric oxide in the exhaled air is less than about 1.5 ppb, and/or that the genetic mutation is present,

wherein the premature infant is less than 30 weeks gestational age.

4. The method of claim 3 , wherein the infant is treated with decreasing dosages of inhaled nitric oxide.

5. The method of claim 4 , wherein an initial dose of 20 ppm is administered for 48-96 hours, and subsequent doses of 10, 5 and 2 ppm are administered at weekly intervals thereafter.

6. The method of claim 3 , wherein treatment is initiated at 5-14 days after birth.

7. The method of claim 3 , wherein the infant is treated for 20-30 days.

Assignments (21)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2026
From: MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY
To: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED COMPANY
Reel/Frame 075393/0361 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF US PATENT 10828415 AND REMOVE IT FROM THE LISTING PREVIOUSLY RECORDED ON REEL 72331 FRAME 1. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Mar 6, 2026
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 075021/0204 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF US PATENT 10828415 AND REMOVE IT FROM THE LISTING PREVIOUSLY RECORDED ON REEL 73375 FRAME 395. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Mar 6, 2026
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 075021/0263 →
SECURITY INTEREST Recorded Oct 28, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 073375/0395 →
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 043601, FRAME 0025 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 065610/0233 →
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 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 →
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 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 →
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 PATENTS Recorded Aug 18, 2017
From: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 043601/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2017
From: MALLINCKRODT IP
To: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
Reel/Frame 043125/0504 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2017
From: MALLINCKRODT PHARMA IP TRADING DAC
To: MALLINCKRODT IP
Reel/Frame 043125/0433 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2017
From: MALLINCKRODT CRITICAL CARE FINANCE INC.
To: MALLINCKRODT PHARMA IP TRADING DAC
Reel/Frame 043125/0334 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2017
From: THERAKOS, INC.
To: MALLINCKRODT CRITICAL CARE FINANCE INC.
Reel/Frame 043125/0211 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2017
From: INO THERAPEUTICS LLC
To: THERAKOS, INC.
Reel/Frame 043125/0167 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2017
From: GREENE, DOUGLAS STUART; MEDICIS, JOSEPH J.; POTENZIANO, JIM
To: INO THERAPEUTICS LLC
Reel/Frame 043125/0096 →