IP Library Granted Patent US 10,376,602
Granted Patent B2
US 10,376,602 · App. 15/719,827 · Granted Aug 13, 2019

Methods for diagnosing and monitoring eosinophilic esophagitis

Inventors: Leonard F. Pease (Bountiful, UT); Hedieh Saffari (Salt Lake City, UT); Gerald J. Gleich (Salt Lake City, UT); Kristin M. Leiferman (Salt Lake City, UT); Kathryn A. Peterson (Salt Lake City, UT); Russell Morris Condie (Salt Lake City, UT)
Assignee: UNIVERSITY OF UTAH RESEARCH FOUNDATION
A61K51/0491A61K51/08
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Quick Facts
Patent No.
US 10,376,602
App. No.
15/719,827
Granted
Aug 13, 2019
Kind
B2
Abstract

Disclosed are compositions and methods for diagnosing eosinophilic esophagitis in a subject. Also disclosed are methods for monitoring the course of eosinophilic esophagitis in a subject before, during, and after treatment. In another aspect, disclosed is a method of diagnosing eosinophilic esophagitis or eosinophilic diseases in a subject, comprising detecting an eosinophil granule protein in the mucosal tissue of the esophagitis or other organs in a subject.

Claims (47)

1. A method of producing a medical image of an organ, wherein the organ is an ovary, a breast, a brain, a muscle, a heart, a lung, a stomach, a proximal large intestine, a distal large intestine, a small intestine, a pancreas, a thyroid, skin, an eye, a testicle, a thymus, a gallbladder or a uterus in a subject, said method comprising:

administering to a subject radiolabeled heparin wherein the radiolabeled heparin binds to one or more eosinophil granule proteins in the tissue of the subject's ovary, breast, brain, muscle, heart, lung, stomach, proximal large intestine, distal large intestine, small intestine, pancreas, thyroid, skin, eye, testicle, thymus, gallbladder or uterus, wherein said binding generates a radiolabeled heparin eosinophil granule protein complex, wherein the eosinophil granule protein is major basic protein 1 (MBP-1), major basic protein 2 (MBP-2), eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), or eosinophil peroxidase (EPO), and

detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the subject's ovary, breast, brain, muscle, heart, lung, stomach, proximal large intestine, distal large intestine, small intestine, pancreas, thyroid, skin, eye, testicle, thymus, gallbladder or uterus,

whereby detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the subject's ovary, breast, brain, muscle, heart, lung, stomach, intestines, pancreas, thyroid, skin, eye, testicle, thymus, gallbladder or uterus produces a medical image of the ovary, the breast, the brain, the muscle, the heart, the lung, the stomach, the proximal large intestine, the distal large intestine, the small intestine, the pancreas, the thyroid, the skin, the eye, the testicle, the thymus, the gallbladder the or uterus in the subject.

2. The method of claim 1 , wherein the radiolabel is 99m Tc.

3. A method of producing a medical image of a major blood organ in a subject, said method comprising:

administering to a subject radiolabeled heparin wherein the radiolabeled heparin binds to one or more eosinophil granule proteins in the tissue of the subject's major blood organ, wherein said binding generates a radiolabeled heparin eosinophil granule protein complex, wherein the eosinophil granule protein is major basic protein 1 (MBP-1), major basic protein 2 (MBP-2), eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), or eosinophil peroxidase (EPO), and

detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the subject's major blood organ,

whereby detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the subject's major blood organ produces a medical image of the major blood organ in the subject.

4. The method of claim 3 , wherein the major blood organ is the liver, spleen, kidneys, or bladder.

5. The method of claim 1 , wherein the radiolabeled heparin is administered to the subject orally.

6. The method of claim 1 , wherein the radiolabeled heparin is administered to the subject by intravenous injection.

7. The method of claim 1 , wherein the radiolabeled heparin is administered to the subject topically or intra-nasally.

8. The method of claim 1 , wherein the subject is a human.

9. The method of claim 1 , wherein the radiolabeled heparin eosinophil granule protein complex is detected using one or more of single-photon emission computed tomography (SPECT), positron emission tomography (PET) scans, X-ray, conventional or computed tomography (CT), a combination of SPECT and CT, or magnetic resonance imaging (MRI).

10. A method of diagnosing an eosinophilic disease in a subject, the method comprising:

administering to a subject radiolabeled heparin, wherein the radiolabeled heparin binds to one or more eosinophil granule proteins in the tissue of a subject's organ, wherein said organ is a major blood organ, an ovary, a breast, a muscle, a heart, a lung, a stomach, a proximal large intestine, a distal large intestine, a small intestine, a pancreas, skin, an eye, a testicle, a thymus, a gallbladder or a uterus, wherein said binding generates a radiolabeled heparin eosinophil granule protein complex, wherein the eosinophil granule protein is major basic protein 1 (MBP-1), major basic protein 2 (MBP-2), eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), or eosinophil peroxidase (EPO), and

detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the organ,

whereby detecting the radiolabeled heparin eosinophil granule protein complex in the mucosal tissue of the organ diagnoses an eosinophilic disease in the subject.

11. A method of detecting a change in an eosinophilic disease in a subject diagnosed with an eosinophilic disease, comprising:

a) producing a first medical image of an organ in a subject diagnosed with an eosinophilic disease according to the method of claim 1 or claim 3 ;

b) producing a second medical image of the organ in the subject of step (a), according to the method of claim 1 or claim 3 ; and

c) comparing the medical image of step (b) with the medical image of step (a), whereby detecting a change in the medical image of step (b) compared to the medical image of step (a) detects a change in the eosinophilic disease in the subject.

12. A method of detecting eosinophil degranulation in a subject, the method comprising:

administering to a subject radiolabeled heparin wherein the radiolabeled heparin binds to one or more eosinophil granule proteins in the tissue of a subject's organ, wherein said organ is a major blood organ, an ovary, a breast, a muscle, a heart, a lung, a stomach, a proximal large intestine, a distal large intestine, a small intestine, a pancreas, skin, an eye, a testicle, a thymus, a gallbladder or a uterus, wherein said binding generates a radiolabeled heparin eosinophil granule protein complex, wherein the eosinophil granule protein is major basic protein 1 (MBP-1), major basic protein 2 (MBP-2), eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), or eosinophil peroxidase (EPO), and

detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the subject's organ,

whereby detecting the radiolabeled heparin eosinophil granule protein complex in the tissue of the organ detects eosinophil degranulation in the subject.

13. The method of claim 3 , wherein the radiolabel is 99m Tc.

14. The method of claim 9 , wherein the radiolabel is 99m Tc.

15. The method of claim 12 , wherein the radiolabel is 99m Tc.

16. The method of claim 3 , wherein the radiolabeled heparin is administered to the subject orally.

17. The method of claim 9 , wherein the radiolabeled heparin is administered to the subject orally.

18. The method of claim 11 , wherein the radiolabeled heparin is administered to the subject orally.

19. The method of claim 3 , wherein the radiolabeled heparin is administered to the subject by intravenous injection.

20. The method of claim 9 , wherein the radiolabeled heparin is administered to the subject by intravenous injection.

21. The method of claim 11 , wherein the radiolabeled heparin is administered to the subject by intravenous injection.

22. The method of claim 3 , wherein the radiolabeled heparin is administered to the subject topically or intra-nasally.

23. The method of claim 9 , wherein the radiolabeled heparin is administered to the subject topically or intra-nasally.

24. The method of claim 11 , wherein the radiolabeled heparin is administered to the subject topically or intra-nasally.

25. The method of claim 3 , wherein the subject is a human.

26. The method of claim 9 , wherein the subject is a human.

27. The method of claim 11 , wherein the subject is a human.

28. The method of claim 3 , wherein the radiolabeled heparin eosinophil granule protein complex is detected using one or more of single-photon emission computed tomography (SPECT), positron emission tomography (PET) scans, X-ray, conventional or computed tomography (CT), a combination of SPECT and CT, or magnetic resonance imaging (MRI).

29. The method of claim 9 , wherein the radiolabeled heparin eosinophil granule protein complex is detected using one or more of single-photon emission computed tomography (SPECT), positron emission tomography (PET) scans, X-ray, conventional or computed tomography (CT), a combination of SPECT and CT, or magnetic resonance imaging (MRI).

30. The method of claim 11 , wherein the radiolabeled heparin eosinophil granule protein complex is detected using one or more of single-photon emission computed tomography (SPECT), positron emission tomography (PET) scans, X-ray, conventional or computed tomography (CT), a combination of SPECT and CT, or magnetic resonance imaging (MRI).

31. The method of claim 9 , wherein the major blood organ is the liver, spleen, kidneys, or bladder.

32. The method of claim 11 , wherein the major blood organ is the liver, spleen, kidneys, or bladder.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2021
From: SAFFARI, HEDIEH; GLEICH, GERALD J.; LEIFERMAN, KRISTIN M.; PETERSON, KATHRYN A.; CONDIE, RUSSELL MORRIS
To: UNIVERSITY OF UTAH
Reel/Frame 057293/0472 →
CONFIRMATORY LICENSE Recorded Nov 18, 2020
From: UNIVERSITY OF UTAH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 054474/0822 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 29, 2019
From: PEASE, LEONARD F.; SAFFARI, HEDIEH; GLEICH, GERALD J.; LEIFERMAN, KRISTIN M.; PETERSON, KATHRYN A.; CONDIE, RUSSELL MORRIS
To: UNIVERSITY OF UTAH
Reel/Frame 049024/0358 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 29, 2019
From: UNIVERSITY OF UTAH
To: UNIVERSITY OF UTAH RESEARCH FOUNDATION
Reel/Frame 049024/0377 →
Continuity (4)
Continuation 14402070
Provisional Application 61786909 · Mar 15, 2013
Provisional Application 61688650 · May 18, 2012
Related Publication 20180036440A1 · Feb 8, 2018