# US 10,765,697 B2 · Method and treating renal disease

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- Number: US 10,765,697 B2
- Document ID: US10765697B2
- Status: Granted
- Kind: B2
- Application number: 16/227,003
- Filed: 2018-12-20
- Published: 2019-05-02
- Granted: 2020-09-08
- Earliest claimed: 2010-10-19
- Assignees: L&F Research LLC
- Applicants: L & F Research LLC
- Inventors: Alessia Fornoni; Sandra Merscher-Gomez
- Web page: https://patentgrep.com/patent/US10765697B2

## CPC

- A61K 31/724: Cyclodextrins
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 13/12: of the kidneys
- C12Q 1/6897: involving reporter genes operably linked to promoters
- G01N 33/5044: {involving specific cell types}
- G01N 33/5091: {for testing the pathological state of an organism}
- G01N 33/56966: {Animal cells}
- G01N 2800/245: Transplantation related diseases, e.g. graft versus host disease
- G01N 2800/347: Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
- G01N 2800/50: Determining the risk of developing a disease
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Assays, methods and kits for predicting a subject's (e.g., human) risk of primary glomerulopathy, secondary glomerulopathy or recurrence (e.g., post-transplant recurrence) of any glomerular disease include examining cells for the presence or absence of cytoskeletal disruptions or rearrangements and examining cells for modulation of expression and/or activity of markers such as SMPDL-3b. Assays for predicting if a diabetic subject will develop kidney disease or a patient with FSGS will develop recurrent disease after transplant also include examining cells for the presence or absence of cytoskeletal disruptions or rearrangements and examining cells for modulation of expression and/or activity of markers such as SMPDL-3b. Also described herein are compositions and methods for treating and preventing the aforementioned disorders.

## Claims

### Claim 1

A method of treating a primary or secondary proteinuric glomerular disorder or recurrent proteinuric glomerular disease in a subject in need thereof, comprising administering a therapeutically effective amount of a composition comprising hydroxypropyl-beta cyclodextrin, or methyl-beta cyclodextrin, or both, as an active agent.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cyclodextrin active agent restores physiological lipid content in podocytes or physiological lipid-related protein content in podocytes of the kidney of the subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cyclodextrin active agent is hydroxypropyl β cyclodextrin (HPBCD).

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition is administered to the subject at one or more time points selected from the group consisting of prior to kidney transplantation, during kidney transplantation, and subsequent to kidney transplantation.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

The method of claim 1, wherein the effective amount of the composition comprising the cyclodextrin active agent is capable of at least one of increasing SMPDL-3b levels in podocytes of the kidney of the subject, restoring cytoskeleton rearrangements in podocytes of the kidney of the subject, and decreasing or preventing B7-1 expression or activity in podocytes of the kidney of the subject.

### Claim 7 (depends on 1)

The method of claim 1, wherein the effective amount of the composition comprising the cyclodextrin active agent is effective for preventing apoptosis of podocytes, preventing disruption of podocyte cytoskeleton, preventing accumulation of cholesterol and/or lipids in podocytes of the kidney of the subject.

### Claim 8 (depends on 1)

The method of claim 1, wherein the cyclodextrin active agent is methyl-beta cyclodextrin (MBCD).

### Claim 9 (depends on 1)

The method of claim 1, wherein the cyclodextrin active agent is administered in an amount effective for reducing at least one of plasma membrane cholesterol, plasma membrane lipids, cellular cholesterol, and cellular lipids in podocytes of the kidney of the subject.

### Claim 10 (depends on 1)

The method of claim 1, wherein the primary glomerulopathy, secondary glomerulopathy, or recurrence of a glomerular disease is selected from the group consisting of post-transplant recurrence of a glomerular disease, focal segmental glomerulosclerosis (FSGS), membranous nephropathy, minimal change disease, IgA nephropathy, membranoproliferative glomerulopathy, diabetic nephropathy, lupus nephritis, myeloma kidney, hypertensive nephrosclerosis, paucimmune glomerulonephritis, preeclampsia, amyloidosis, cryoglobulinemia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, scleroderma kidney, Alport's glomerulopathy, transplant glomerulopathy.

### Claim 11 (depends on 1)

The method of claim 1, wherein the composition is administered in an amount effective for preserving podocyte function in the subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein the composition further comprises a drug selected from the group consisting of an immunosuppressive agent, ACTH agonist, insulin sensitizer, GH antagonist, antinflammatory medication, vitamin D derivative, RAS system inhibitor, aldosterone inhibitor, HMG-CoA reductase inhibitor, cholesterol absorption inhibitor, bile acid sequestrant, bile acid resin, niacin, niacin derivative selected from the group consisting of Niceritrol, Nicotinyl alcohol and Acipimox, fibrate, cholesteryl ester transfer protein (CETP) inhibitor, Acetyl-Coenzyme A acetyltransferase (ACAT) inhibitor, and microsomal triglyceride transport inhibitor.

### Claim 13 (depends on 1)

The method of claim 1, wherein the composition is administered in an amount effective for treating proteinuria in the subject.