IP Library › Granted Patent US 12,282,019
Granted Patent B2
US 12,282,019 · App. 17/957,853 · Granted Apr 22, 2025

Compositions and methods to detect gastrointestinal disease

Inventors: Sunyoung Kim (New Orleans, LA); Zeromeh Gerber (Las Vegas, NV); Duna Penn (New Orleans, LA); Carl Sabottke (New Orleans, LA); Rebecca Buckley (Metairie, LA)
Assignee: THE BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE
G01N33/573A23K10/00A23K20/195A23L33/17A23L33/40A61K35/741A61P1/00A61P29/00C07K16/40C12Q1/42C12Q1/68A23V2002/00A61K9/0019A61K9/0053G01N2333/916G01N2800/065
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Quick Facts
Patent No.
US 12,282,019
App. No.
17/957,853
Granted
Apr 22, 2025
Kind
B2
Abstract

This invention comprises compositions and methods to detect and treat gastrointestinal diseases.

Claims (28)

1. A method of identifying an infant afflicted with early-stage necrotizing enterocolitis, the method comprising:

detecting the presence of at least one early-stage necrotizing enterocolitis biomarker in a stool sample from the infant,

wherein the early-stage necrotizing enterocolitis biomarker comprises increased iAP protein level compared with age-matched controls, increased total protein level compared with age-matched controls, or a combination thereof,

wherein the early-stage necrotizing enterocolitis biomarker is indicative of infant afflicted with early-stage necrotizing enterocolitis; and

treating the infant afflicted with early-stage necrotizing enterocolitis, wherein treating comprises administering an effective amount of an antibiotic, a probiotic, an intravenous fluid, an iAP replacement composition, a small molecule effector of catalytic activity, an anti-inflammatory agent, parenteral or intravenous nutrition, a biologic, or a prebiotic; withholding oral feeding; surgery; or a combination thereof.

2. The method of claim 1 , further comprising diagnosing the infant as having early-stage necrotizing enterocolitis if the total protein level in the sample is greater than about 1.0 mg/ml, if the level of iAP protein is greater than 10.7% of a positive control sample, or a combination thereof.

3. A method for screening the presence of an early-stage necrotizing enterocolitis signature, the method comprising:

detecting the presence of at least one early-stage necrotizing enterocolitis biomarker in a stool sample from an infant, wherein the early-stage necrotizing enterocolitis biomarker comprises increased iAP protein level compared with age-matched controls, increased total protein level compared with age-matched controls, or a combination thereof, thereby providing a necrotizing enterocolitis signature that is indicative of necrotizing enterocolitis; and

treating the infant afflicted with necrotizing enterocolitis, administering an effective amount of an antibiotic, a probiotic, an intravenous fluid, an iAP replacement composition, a small molecule effector of catalytic activity, an anti-inflammatory agent, parenteral or intravenous nutrition, a biologic, or a prebiotic; withholding oral feeding; surgery; or a combination thereof.

4. The method of claim 3 , wherein the early-stage necrotizing enterocolitis biomarker is total protein level in the sample greater than about 1.0 mg/ml, iAP protein greater than 10.7% of a positive control sample, or a combination thereof.

5. A method for determining the prognosis of an infant afflicted with necrotizing enterocolitis, the method comprising:

detecting the presence of at least one necrotizing enterocolitis biomarker in a stool sample from the infant, wherein the necrotizing enterocolitis biomarker comprises increased iAP protein level compared with age-matched controls, increased total protein level compared with age-matched controls, or a combination thereof, thereby providing a necrotizing enterocolitis signature that is indicative of necrotizing enterocolitis;

comparing the presence of the at least one necrotizing enterocolitis biomarker to a reference level of the at least one necrotizing enterocolitis biomarker; and

determining a prognosis for the infant, wherein a poor prognosis is indicated by an increase of iAP protein level compared to a positive control sample, increased total protein level compared with age-match controls, or a combination thereof.

6. The method of claim 5 , wherein the method is carried out prior to administering an anti-NEC treatment to the infant.

7. The method of claim 5 , further comprising identifying the infant as likely to benefit from administration of an anti-NEC treatment when the patient is determined to have an increase of iAP protein level compared with an age-matched control, an increased total protein level compared with an age-matched control, or a combination thereof.

8. The method of claim 5 , further comprising treating the infant, wherein treating comprises administering an effective amount of an antibiotic, a probiotic, an intravenous fluid, an iAP replacement composition, a small molecule effector of catalytic activity, an anti-inflammatory agent, parenteral or intravenous nutrition, a biologic, or a prebiotic; withholding oral feeding; surgery; or a combination thereof.

9. The method of any one of claims 1, 3, or 5 , wherein the infant is a premature infant.

10. The method of any one of claims 1, 3, or 5 , wherein the detecting comprises performing an assay to determine total protein level, intestinal alkaline phosphatase protein level, or a combination thereof in the sample.

11. The method of claim 10 , wherein the assay comprises an immunoassay, a colorimetric assay, a fluorimetric assay, a radioisotope assay, or a combination thereof.

12. The method of claim 11 , wherein the immunoassay comprises a western blot assay, an enzyme-linked immunosorbent assay (ELISA), immunoprecipitation or a combination thereof.

13. The method of claim 1, 3, or 5 , further comprising incubating the biological sample with an agent that binds intestinal alkaline phosphatase (iAP).

14. The method of claim 13 , wherein the agent comprises an anti-iAP antibody or an anti-AP antibody.

15. The method of claim 10 , wherein the assay comprises a kinetic assay or endpoint assay.

16. The method of claim 15 , wherein the kinetic assay comprises 4-methylumbelliferyl phosphate, p-Nitrophenyl phosphate, an assay to detect ATP hydrolysis or its products, or a combination thereof.

17. The method of claim 1, 3, or 5 , wherein the necrotizing enterocolitis biomarker further comprises decreased iAP enzymatic activity compared with age-matched controls.

18. The method of claim 17 , further comprising diagnosing the infant as having necrotizing enterocolitis if the iAP enzymatic activity is lower than about 979 mU/mg.

19. The method of claim 17 , wherein the detecting comprises an assay to determine intestinal alkaline phosphatase enzyme activity.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 4, 2025
From: KIM, SUNYOUNG; GERBER, ZEROMEH; PENN, DUNA; SABOTTKE, CARL; BUCKLEY, REBECCA
To: BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE, THE
Reel/Frame 070107/0147 →
Continuity (7)
Continuation 16267120 · Feb 4, 2019
Continuation In Part PCTUS2017045588 · Aug 4, 2017
Provisional Application 62524306 · Jun 23, 2017
Provisional Application 62467487 · Mar 6, 2017
Provisional Application 62378820 · Aug 24, 2016
Provisional Application 62371131 · Aug 4, 2016
Related Publication 20230184769A1 · Jun 15, 2023
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