# US 2014/0193388 A1 · Modified Phosphatases

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- Number: US 2014/0193388 A1
- Document ID: US20140193388A1
- Status: Published application
- Kind: A1
- Application number: 14/020,269
- Filed: 2013-09-06
- Published: 2014-07-10
- Earliest claimed: 2007-04-27
- Assignees: AM-Pharma B.V.
- Applicants: Am-Pharma B.V.
- Inventors: MARKWIN PAUL VELDERS; LUIGI JOHANNES CORNELIUS JONK; WILLEM RAABEN; MARTY BERNARDUS FRANSISCUS WULFERINK
- Web page: https://patentgrep.com/patent/US20140193388A1

## CPC

- C12N 9/16: acting on ester bonds (3.1)
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C12Y 301/03001: Alkaline phosphatase (3.1.3.1)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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 invention relates to phosphatases and more in specific to (genetically) modified phosphatases, pharmaceutical compositions comprising (genetically) modified phosphatases and the use of (genetically) modified phosphatases for treating or curing for example sepsis, inflammatory bowel disease or other inflammatory diseases, or renal failure. The invention further relates to a method for producing phosphatases.

## Claims

### Claim at position 1

1-35. (canceled)

### Claim 36

An alkaline phosphatase, wherein the alkaline phosphatase is isolated or recombinant and comprises: a crown domain, and a catalytic domain, wherein the crown domain and the catalytic domain are obtained from different alkaline phosphatases.

### Claim 37 (depends on 36)

The alkaline phosphatase of claim 36, wherein the crown domain is the crown domain of ALPP and the catalytic domain is the catalytic domain of ALPI.

### Claim 38 (depends on 36)

The alkaline phosphatase of claim 36, wherein the crown domain is the crown domain of ALPI and the catalytic domain is the catalytic domain of ALPP.

### Claim 39 (depends on 36)

The alkaline phosphatase of claim 36, further comprising a mutation or a deletion of the amino acid sequence encompassing the consensus glycosylphosphatidylinositol (“GPI”) signal sequence in the GPI signal sequence, further wherein the modification or deletion results in a secreted phosphatase.

### Claim 40

An isolated or recombinant phosphatase comprising a mutation in the vicinity of a catalytic residue and/or in a metal ion-coordinating phosphate-binding pocket, wherein the mutation is a mutation as depicted in Table 4, 5, or 6.

### Claim 41 (depends on 40)

The phosphatase of claim 40, further comprising a modification in the glycosylphosphatidylinositol (“GPI”) signal sequence wherein the modification results in a non-GPI anchored phosphatase and/or comprising a crown domain and a catalytic domain from different phosphatases.

### Claim 42 (depends on 36)

A nucleic acid sequence encoding the alkaline phosphatase of claim 36.

### Claim 43 (depends on 42)

A vector comprising the nucleic acid of claim 42.

### Claim 44 (depends on 42)

A host cell comprising the nucleic acid of claim 42.

### Claim 45 (depends on 39)

A nucleic acid sequence encoding the phosphatase of claim 39.

### Claim 46 (depends on 45)

A vector comprising the nucleic acid of claim 45.

### Claim 47 (depends on 45)

A host cell comprising the nucleic acid of claim 45.

### Claim 48 (depends on 40)

A nucleic acid sequence encoding the phosphatase of claim 40.

### Claim 49 (depends on 48)

A vector comprising the nucleic acid of claim 48.

### Claim 50 (depends on 48)

A host cell comprising the nucleic acid of claim 48.

### Claim 51 (depends on 36)

A method for producing the phosphatase of claim 36, the method comprising: culturing a host cell able to express the phosphatase in a medium comprising Zn2+ and allowing the cell to produce the phosphatase.

### Claim 52 (depends on 51)

The method according to claim 51, further comprising isolating the phosphatase.

### Claim 53 (depends on 51)

A phosphatase produced by the method according to claim 51.

### Claim 54 (depends on 36)

A pharmaceutical composition comprising the phosphatase of claim 36.

### Claim 55 (depends on 53)

A pharmaceutical composition comprising the phosphatase of claim 53.

### Claim 56 (depends on 36)

A method for treating a subject suffering from sepsis, inflammatory bowel disease, inflammation of the epithelial lining of the gut, other inflammatory disease, reduced renal function, and/or renal failure, the method comprising: administering to the subject an effective amount of the alkaline phosphatase of claim 36.

### Claim 57 (depends on 38)

A method for dephosphorylating a substrate in an environment having a Zn2+ concentration lower than 10 μM, the method comprising: utilizing the alkaline phosphatase of claim 38 to dephosphorylate the substrate.

### Claim 58 (depends on 37)

A method for treating a subject suffering from or believed to be suffering from reduced renal function, renal failure and/or a disease which is accompanied by Zn2+ deficiency, the method comprising: administering an effective amount of the alkaline phosphatase of claim 37 to the subject.

### Claim 59 (depends on 58)

The method according to claim 58, wherein the disease comprises an inflammatory disease and/or is accompanied by intestinal integrity damage.

### Claim 60 (depends on 59)

The method according to claim 59, wherein the disease is selected from the group consisting of autoimmune diseases, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel disease, inflammation of the epithelial lining of the gut, sepsis, neurodermitis, osteitis, and diseases identified in Table 10.

### Claim 61 (depends on 36)

The alkaline phosphatase of claim 36, wherein at least one of the different alkaline phosphatases is a human phosphatase.

### Claim 62 (depends on 40)

The isolated or recombinant phosphatase of claim 40, wherein the isolated or recombinant phosphatase is a human phosphatase and/or an alkaline phosphatase.

### Claim 63 (depends on 51)

The method according to claim 51, wherein the host cell is a mammalian cell.

### Claim 64 (depends on 56)

The method according to claim 56, wherein the subject is a human.

### Claim 65 (depends on 57)

The method according to claim 57, wherein the substrate is an adenosine phosphate.

### Claim 66 (depends on 58)

The method according to claim 58, wherein the subject is a human.