# US 11,992,533 B2 · Methods of treatment of HLA-B27 related inflammatory diseases and compositions related to same

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- Number: US 11,992,533 B2
- Document ID: US11992533B2
- Status: Granted
- Kind: B2
- Application number: 17/673,543
- Filed: 2022-02-16
- Published: 2022-08-04
- Granted: 2024-05-28
- Earliest claimed: 2017-03-31
- Assignees: Michael Stalhamer
- Applicants: Alma Bio Therapeutics
- Inventors: Irun Cohen; Denis Ravel; Raanan Margalit; Binah Baum
- Web page: https://patentgrep.com/patent/US11992533B2

## CPC

- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 39/0008: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- 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

## Abstract

The present disclosure provides methods and compositions for treatment of an HLA-B27-associated autoimmune inflammatory disorder by administration of nucleic acid encoding HSP90 or an active fragment thereof.

## Claims

### Claim 1

A method of treating or preventing a spondyloarthropathy in a subject having, or at risk of developing, the spondyloarthropathy, the method comprising:
provided that the subject is HLA-B27 positive, administering to said subject a composition comprising a nucleic acid molecule encoding a mammalian heat shock protein 90 (HSP90), or an active fragment thereof, wherein the nucleic acid molecule is operatively linked to one or more transcription control sequences.

### Claim 2 (depends on 1)

The method of claim 1, comprising:
a) identifying said subject as being HLA-B27 positive, and
b) administering to said HLA-B27 positive subject, the composition comprising the nucleic acid molecule encoding the mammalian HSP90, or active fragment thereof, wherein the nucleic acid molecule is operatively linked to one or more transcription control sequences.

### Claim 3 (depends on 2)

The method of claim 2, wherein identifying said subject as being HLA-B27 positive comprises determining the HLA-B27 status of said subject by detection of the HLA-B27 antigen in a sample obtained from said subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein said composition is administered to said subject in an amount and for a period of time to provide for improvement in at least one disease symptom of said spondyloarthropathy.

### Claim 5 (depends on 1)

The method of claim 1, wherein the spondyloarthropathy is anklyosing spondylitis, reactive arthritis, psoriatic arthritis or enteropathic arthritis.

### Claim 6 (depends on 5)

The method of claim 5, wherein said spondyloarthropathy is anklyosing spondylitis.

### Claim 7 (depends on 1)

The method of claim 1, wherein said subject is a human.

### Claim 8 (depends on 7)

The method of claim 7, wherein said subject is male.

### Claim 9 (depends on 7)

The method of claim 7, wherein the mammalian HSP90 is human HSP90.

### Claim 10 (depends on 1)

The method of claim 1, wherein said administering is by injection.

### Claim 11 (depends on 4)

The method of claim 4, wherein the composition is administered weekly for a period of at least 4 weeks.

### Claim 12 (depends on 11)

The method of claim 11, wherein the composition is administered in an amount of from about 0.005 mg/kg to about 1 mg/kg of the nucleic acid molecule encoding the mammalian HSP90, or an active fragment thereof, to the body weight of the subject.

### Claim 13 (depends on 12)

The method of claim 12, wherein the composition is administered in an amount of from about 0.01 mg/kg to about 0.5 mg/kg of the nucleic acid molecule encoding the mammalian HSP90, or an active fragment thereof, to the body weight of the subject.

### Claim 14 (depends on 12)

The method of claim 12, wherein the composition is administered in an amount of from about 0.10 mg/kg to about 0.30 mg/kg of the nucleic acid molecule encoding the mammalian HSP90, or an active fragment thereof, to the body weight of the subject.

### Claim 15 (depends on 1)

The method of claim 1, wherein the nucleic acid molecule is not encapsulated and is not contained in a virus.

### Claim 16 (depends on 1)

The method of claim 1, wherein the composition comprises a pharmaceutically acceptable alkali metal salt.

### Claim 17 (depends on 16)

The method of claim 16, wherein the pharmaceutically acceptable alkali metal salt is sodium chloride.

### Claim 18 (depends on 1)

The method of claim 1, wherein the composition comprises a delivery vehicle selected from the group consisting of a liposome, a micelle, and an emulsion.

### Claim 19 (depends on 1)

The method of claim 1, wherein the composition comprises a lipid particle.

### Claim 20 (depends on 1)

The method of claim 1, wherein the composition comprises a cationic lipid, polyethylene glycol, polylysine, poloxamer, chitosan, polyL glutamate, or poly(lactide-co-glycolide) (PLG).
