IP Library › Granted Patent US 12,422,432
Granted Patent B2
US 12,422,432 · App. 18/459,908 · Granted Sep 23, 2025

Methods for assessing mucosal healing in inflammatory bowel disease patients

Inventors: Anjali Jain (San Diego, CA); Venkateswarlu Kondragunta (San Diego, CA); Michael Hale (San Diego, CA)
Assignee: Prometheus Laboratories Inc.
G01N33/564G01N33/6893G01N2800/065G01N2800/52
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Quick Facts
Patent No.
US 12,422,432
App. No.
18/459,908
Granted
Sep 23, 2025
Kind
B2
Abstract

The present disclosure provides methods for assessing mucosal healing in a patient with Crohn's Disease. The methods include detecting expression levels of analytes in a serum sample from a patient, and applying a mathematical algorithm to the expression levels, thereby producing a Mucosal Healing Index score for the patient. The present disclosure also provides kits that include two or more binding partners, each or which is capable of binding a different analyte measured in the disclosed mucosal healing assessment methods.

Claims (25)

1. A method for assessing mucosal healing in a patient with Crohn's Disease (CD), the method comprising:

detecting in a serum sample from a patient an expression level of each of biomarkers selected from the group consisting of C-Reactive Protein (CRP), Serum Amyloid 1 (SAA1), Matrix Metalloproteinase 1 (MMP-1), Matrix Metalloproteinase 3 (MMP-3), and Matrix Metalloproteinase 9 (MMP-9); and

applying a mathematical algorithm to the expression levels of the biomarkers, thereby producing a Mucosal Healing Index (MHI) score for the patient; and

administering an effective amount of a therapeutic agent to the patient based, at least in part, on the MHI score.

2. The method of claim 1 , wherein the detecting comprises contacting the serum sample with a binding partner wherein each binding partner is an antibody for each of the biomarkers and detecting binding between each biomarker and its respective binding partner.

3. The method of claim 1 , further comprising determining that the patient has a high probability of being in remission or having mild endoscopic disease when the MHI score is less than or equal to 40 on a scale from 0 to 100.

4. The method of claim 1 , further comprising determining that the patient has a high probability of having endoscopically active disease when the MHI score is greater than or equal to 50 on a scale from 0 to 100.

5. The method of claim 4 , wherein:

(i) the high probability of having endoscopically active disease is greater than or equal to 87%; and/or

(ii) the endoscopically active disease corresponds to a Crohn's Disease Endoscopic Index of Severity (CDEIS) of greater than or equal to 3 (CDEIS≥3).

6. The method of claim 1 , further comprising determining that the patient has a moderate probability of having endoscopically active disease when the MHI score is between 40 and 50 on a scale from 0 to 100.

7. The method of claim 6 , wherein the moderate probability of having endoscopically active disease is greater than or equal to 78%.

8. The method of claim 1 , wherein the mathematical algorithm comprises two or more models relating the expression levels of the biomarkers to an endoscopic score.

9. The method of claim 8 , wherein:

(i) one or more of the two or more models are derived by using classification and regression trees, and/or one or more of the two or more models are derived by using ordinary least squares regression to model diagnostic specificity;

(ii) one or more of the two or more models are derived by using random forest learning classification, and/or one or more of the two or more models are derived by using quantile classification; or

(iii) one or more of the two or more models are derived by using logistic regression to model diagnostic sensitivity, and/or one or more of the two or more models are derived by using logistic regression to model diagnostic specificity.

10. The method of claim 1 , wherein the therapeutic agent comprises one or more biologic agents, conventional drugs, nutritional supplements, or combinations thereof.

11. The method of claim 1 , wherein:

(i) the patient is receiving a therapy, and the method assesses mucosal healing by determining the efficacy of the therapy;

(ii) the method assesses mucosal healing at colonic, ileocolonic, and/or ileal disease locations in the patient;

(iii) the method assesses mucosal healing in the patient after surgery;

(iv) the method assesses mucosal healing by identifying post-operative, endoscopic recurrence in the patient; or

(v) the method assesses mucosal healing by predicting or monitoring the mucosal status in the patient.

12. The method of claim 1 , comprising detecting in a serum sample from a patient an expression level of an additional biomarker, wherein the additional biomarker comprises one or more of Angiotensin 1 (Ang1), Angotensin 2 (Ang2), Carcinoembryonic Antigen-related Cell Adhesion Molecule (CEACAM1), Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Vascular Cell Adhesion Molecule 1 (VCAM1), Transforming Growth Factor alpha (TGFa), Matrix Metalloproteinase 2 (MMP-2), and Interleukin 7 (IL-7).

Continuity (5)
Continuation 17483462 · Sep 23, 2021
Continuation 16614752
Provisional Application 62561459 · Sep 21, 2017
Provisional Application 62512947 · May 31, 2017
Related Publication 20240230640A1 · Jul 11, 2024
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