Methods of Detecting Anti-folic acid Antibodies and Uses Thereof

• US 20190324046A1
• Filed: 06/14/2017
• Published: 10/24/2019
• Est. Priority Date: 06/14/2016
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: CABRERA, Robert M., FINNELL, Richard H.
• Granted Patent: US 11,313,868 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: G01N 2800/02 Nutritional disorders
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/6854 Immunoglobulins
• CPC Class Codes: G01N 33/82 involving vitamins or their receptors

Abstract

The invention relates to devices and methods for detecting the presence of antibodies to folic acid in a sample.

Claims

1. A device for detecting anti-folic acid antibodies comprising:

a folic acid component and a substrate, wherein the folic acid component is attached to the substrate.

2. The device of claim 1, wherein the folic acid component is selected from the group consisting of folic acid, a folic acid protein conjugate a fragment of folic acid, an analog of folic acid, a substituted version of folic acid, a derivative of folic acid, a fused combination of folic acid and a salt of folic acid.

3. The device of claim 2, wherein the folic acid component comprises a folic acid protein conjugate selected from the group consisting of folic acid conjugated to keyhole limpet hemocyanin (KLH), a fragment of folic acid conjugated to KLH, and folic acid conjugated to biotin.

8. The device of claim 1, wherein the substrate is selected from the group consisting of a bead and a well of a microtiter plate.

36. A kit to detect anti-folic acid antibodies in a sample comprising a device of claim 1.

37. The kit of claim 36, further comprising a labeled biomolecule.

4-7. -7. (canceled)

9. (canceled)

10. A method of detecting an anti-folic acid antibody in a sample, comprising the steps of

a.) obtaining a sample;

b.) contacting the sample with a component that binds to an anti-folic acid antibody; and

c.) detecting binding between the anti-folic acid antibody and the component.

11. The method of claim 10, wherein the component is selected from the group consisting of folic acid, a folic acid protein conjugate, a fragment of folic acid, an analog of folic acid, a substituted version of folic acid, a derivative of folic acid, a fused combination of folic acid and a salt of folic acid.

12. The method of claim 10, wherein the method of detecting the binding comprises

a.) contacting a complex formed by the binding of the anti-folic acid antibody to the component with a labeled biomolecule capable of specifically binding to the complex, and

b.) detecting a signal from the labeled biomolecule.

18. A method of diagnosing a subject with a pathology associated with increased or decreased levels of anti-folic acid antibodies or identifying a subject at risk of developing a pathology associated with increased or decreased levels of anti-folic acid antibodies comprising the steps of

a.) obtaining a sample of the subject;

b) detecting an anti-folic acid antibody in the sample according to the method of claim 10;

c.) detecting an increased or decreased level of anti-folic acid antibodies in the sample as compared to a comparator control; and

d.) diagnosing the subject as having a pathology associated with increased or decreased levels of anti-folic acid antibodies or at risk of developing a pathology associated with increased or decreased levels of anti-folic acid antibodies.

19. The method of claim 18, wherein a pathology associated with increased or decreased levels of anti-folic acid antibodies is selected from the group consisting of infertility, a folate responsive blood disorder, a folate-associated cancer risk, a heart or vascular disease, a folate-associated neurological disorder, a folate-associated neurodegenerative disease, a pathology associated with bone development and maintenance, and depression that is not responsive to SSRIs.

22. A method of diagnosing an infant or unborn child with a pathology associated with increased levels of anti-folic acid antibodies or identifying an infant or unborn child at risk of developing a pathology associated with increased levels of anti-folic acid antibodies comprising the steps of

a.) obtaining a sample;

b) detecting an anti-folic acid antibody in the sample according to the method of claim 10;

c.) detecting an increased level of anti-folic acid antibodies in the sample as compared to a comparator control; and

d.) diagnosing the infant as having a pathology associated with increased levels of anti-folic acid antibodies or at risk of developing a pathology associated with increased levels of anti-folic acid antibodies.

23. The method of claim 22, wherein the sample is selected from the group consisting of a serum sample of the infant, a serum sample of the unborn child, and a maternal serum sample.

25. The method of claim 22, wherein the pathology associated with increased levels of anti-folic acid antibodies is a folate responsive birth defect.

26. The method of claim 25 wherein the folate responsive birth defect is selected from the group consisting of:

neural tube defects, heart defects, outflow track defects, septal defects, patent ductus arteriosus, craniofacial defects, gastrointestinal defects, ocular defects, limb abnormalities, cerebral folate deficiency, hereditary folate malabsorption syndrome, and a combination thereof.

28. The method of claim 18 further comprising the step of treating or preventing a pathology associated with increased or decreased levels of anti-folic acid antibodies comprising administering a treatment selected from the group consisting of:

a) administering an folic acid alternative to a subject identified as having anti-folic acid antibodies present in a sample from the subject; and

b) administering a folic acid inhibitor to a subject identified as having decreased levels of anti-folic acid antibodies present in a sample from the subject.

29. The method of claim 28, wherein the folic acid alternative is one of naturally occurring folate and 5-methyltetrahydrofolate (5MTHF).

32. The method of claim 28, wherein the folic acid inhibitor is an anti-folic acid antibody.

34. The method of claim 22 further comprising the step of treating or preventing a pathology associated with increased levels of anti-folic acid antibodies in an infant, wherein anti-folic acid antibodies have been identified in a maternal sample, comprising administering to the infant a folic acid based treatment.

35. The method of claim 34, wherein the folic acid based treatment is one of folic acid, naturally occurring folate and 5MTHF.

13-17. -17. (canceled)

20-21. -21. (canceled)

24. (canceled)

27. (canceled)

30-31. -31. (canceled)

33. (canceled)