# US 12,178,857 B2 · Recombinant alkaline phosphatase for use in treating sepsis-associated acute kidney injury

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- Number: US 12,178,857 B2
- Document ID: US12178857B2
- Status: Granted
- Kind: B2
- Application number: 16/979,117
- Filed: 2019-03-08
- Published: 2020-12-24
- Granted: 2024-12-31
- Earliest claimed: 2018-03-08
- Assignees: AM-Pharma B.V.
- Applicants: AM-Pharma B.V.
- Inventors: Roelof Peter Pickkers; Ravindra Lall Mehta; Patrick Thomas Murray; Michael Joannidis; Erik Jan Van Den Berg; Jacques Salomon Robert Arend
- Web page: https://patentgrep.com/patent/US12178857B2

## CPC

- A61K 38/43: Enzymes; Proenzymes; Derivatives thereof
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 13/12: of the kidneys
- C12Y 301/03001: Alkaline phosphatase (3.1.3.1)
- 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
- C12Y: ENZYMES

## Abstract

The present disclosure relates to the use of alkaline phosphatases, and in particular improved alkaline phosphatases such as RecAP, for the prevention, treatment, cure, or amelioration of the symptoms of acute kidney injury caused, e.g., by sepsis. The application relates to methods of preserving renal function renal function, shortening the duration of renal replacement therapy, increasing the creatinine clearance, decreasing the risk of death in subjects with sepsis-associate acute kidney injury (SA-AKI) or at risk of SA-AKI.

## Claims

### Claim 1

A method to treat sepsis-associated acute kidney disease injury (SA-AKI) in a subject in need thereof comprising administering an effective amount of alkaline phosphatase (AP) to the subject, wherein
(i) the subject has an ECC (endogenous creatinine clearance) rate 15-60 ml/min prior to the treatment with AP or an eGFR (estimated glomerular filtration rate) 15-60 ml/min prior to the treatment with AP,
(ii) the AP is administered in at least one 500 U/kg to 2,000 U/kg dose, and
(iii) the administration of the AP results in an increase in renal function,
wherein the AP is a chimeric AP having 100% sequence identity to the amino acid sequence of SEQ ID NO: 1.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

The method of claim 1, wherein the increase in renal function comprises an increase in ECC with respect to ECC in the absence of treatment or an increase in eGFR with respect to eGFR in the absence of treatment.

### Claim 4 (depends on 1)

The method of claim 1, wherein sepsis is detected less than 96 hours prior to AP administration.

### Claim 5 (depends on 1)

The method of claim 1, wherein the sepsis is detected less than 72 hours prior to SA-AKI detection.

### Claim 6 (depends on 1)

The method of claim 1, wherein treatment is initiated within 24 hours after sepsis is detected.

### Claim 7 (depends on 1)

The method of claim 1, wherein treatment is initiated within 24 hours after SA-AKI is detected.

### Claim 8 (depends on 1)

The method of claim 1, wherein AP is administered once daily.

### Claim 9 (depends on 1)

The method of claim 1, wherein AP is administered intravenously.

### Claim 10 (depends on 1)

The method of claim 1, wherein AP is administered in three daily doses.

### Claim 11 (depends on 1)

The method of claim 1, wherein the AP dose is 0.8 mg/kg or 1.6 mg/kg.

### Claim 12 (depends on 1)

The method of claim 1, wherein the AP dose is 500 U/kg or 1000 U/kg.

### Claim 13 (depends on 1)

The method of claim 1, wherein the administration of at least one dose of AP results in the preservation or increase of glomerular filtration rate (GFR) or eGFR in the subject.