# US 11,898,175 B2 · Treatment of abnormal bone conditions in acid sphingomyelinase deficiency patients

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- Number: US 11,898,175 B2
- Document ID: US11898175B2
- Status: Granted
- Kind: B2
- Application number: 16/641,116
- Filed: 2018-08-22
- Published: 2021-05-13
- Granted: 2024-02-13
- Earliest claimed: 2017-08-24
- Assignees: Genzyme Corporation
- Applicants: Genzyme Corporation
- Inventors: Ana Cristina Scheidt-Puga
- Web page: https://patentgrep.com/patent/US11898175B2

## CPC

- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- C12N 9/16: acting on ester bonds (3.1)
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- C12Y 301/04: Phosphoric diester hydrolases (3.1.4)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES

## Abstract

The invention provides methods of using a human acid sphingomyelinase (e.g., olipudase alfa) in treating an abnormal bone condition in acid sphingomyelinase deficiency patients such as low bone density, high bone marrow burden, and other skeletal abnormalities presented in acid sphingomyelinase deficiency patients.

## Claims

### Claim 1

A method of treating an abnormal bone condition in a patient with acid sphingomyelinase deficiency (ASMD), comprising:
selecting a patient with ASMD for treatment of an abnormal bone condition,
administering to the patient a plurality of doses of recombinant human acid sphingomyelinase (rhASM) over a period of six to thirty months,
measuring a bone indicator of the patient, and
comparing the bone indicator of the patient to the baseline bone indicator of the patient before the administering step, wherein the patient's bone indicator improves after the plurality of doses of rhASM.

### Claim 2 (depends on 1)

The method of claim 1, wherein the bone indicator is
(i) bone mineral density (BMD), wherein the BMD improves after the plurality of doses of rhASM,
(ii) bone marrow burden (BMB), wherein the BMB decreases after the plurality of doses of rhASM,
(iii) bone maturation, wherein the bone maturation improves after the plurality of doses of rhASM, or
(iv) linear growth, wherein the linear growth improves after the plurality of doses of rhASM.

### Claim 3 (depends on 1)

The method of claim 1, wherein the abnormal bone condition is osteopenia or osteoporosis.

### Claim 4 (depends on 1)

The method of claim 1, wherein the patient has Niemann-Pick disease type B.

### Claim 5 (depends on 1)

The method of claim 1, wherein the patient has Niemann-Pick disease type A/B.

### Claim 6 (depends on 1)

The method of claim 1, wherein the patient is an adult patient.

### Claim 7 (depends on 1)

The method of claim 1, wherein the patient is a pediatric patient.

### Claim 8 (depends on 1)

The method of claim 1, wherein
(i) the first two or more doses are escalating doses and are administered at a successively increasing amount,
(ii) the doses after the escalating doses are maintenance doses and are administered in the same amount as or less than the last escalating dose,
(iii) the first dose is in the amount of 0.1 mg/kg and the patient is a pediatric patient,
(iv) the first dose is in the amount of 0.1 mg/kg and the patient is an adult patient,
(v) the highest maintenance dose is in the amount of 0.3 mg/kg to 3 mg/kg,
(vi) the highest maintenance dose is in the amount of 1 mg/kg,
(vii) the highest maintenance dose is in the amount of 2 mg/kg,
(viii) the highest maintenance dose is in the amount of 3 mg/kg,
(ix) the highest maintenance dose is the highest dose tolerated by the patient, and/or
(x) the escalating doses are administered in the order of 0.1 mg/kg, 0.3 mg/kg, 0.3 mg/kg, 0.6 mg/kg, 0.6 mg/kg, 1.0 mg/kg, 2.0 mg/kg, and 3.0 mg/kg.

### Claim 9 (depends on 1)

The method of claim 1, wherein the plurality of doses are administered at an interval of every 2 weeks.

### Claim 10 (depends on 1)

The method of claim 1, wherein the plurality of doses are administered through intravenous injection.

### Claim 11 (depends on 1)

The method of claim 1, wherein the rhASM is olipudase alfa.