# US 12,214,020 B2 · PTH prodrugs

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- Number: US 12,214,020 B2
- Document ID: US12214020B2
- Status: Granted
- Kind: B2
- Application number: 18/464,046
- Filed: 2023-09-08
- Published: 2024-04-18
- Granted: 2025-02-04
- Earliest claimed: 2016-03-01
- Assignees: Ascendis Pharma Bone Diseases A/S
- Applicants: Ascendis Pharma Bone Diseases A/S
- Inventors: Kennett Sprogøe; Felix Cleemann; Guillaume Maitro; Mathias Krusch; Thomas Wegge; Joachim Zettler
- Web page: https://patentgrep.com/patent/US12214020B2

## CPC

- A61K 38/29: Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
- 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)}
- A61K 47/54: the modifying agent being an organic compound
- A61K 47/545: {Heterocyclic compounds (A61K47/558 takes precedence)}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 5/18: of the parathyroid hormones
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 17/14: for baldness or alopecia
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07K 14/575: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695)
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention relates to PTH prodrugs, pharmaceutical compositions comprising such PTH prodrugs and their uses.

## Claims

### Claim 1

A method of treating a patient having hypoparathyroidism comprising administering to the patient a therapeutically effective amount of a compound according to formula 31
or a pharmaceutically acceptable salt thereof, thereby treating hypoparathyroidism in the patient,
wherein PTH(1-34) is parathyroid hormone of the amino acid sequence SEQ ID NO:51, NαS1 is the alpha amino group of the N-terminal serine of SEQ ID NO:51 and 2×10 kDa PEG comprises a branched polyethylene glycol polymer of two arms in which each arm has a molecular weight of about 10 kDa and is a moiety of formula (b)
wherein the dashed line indicates attachment to —S— in compound 31, and each of m and p of each moiety is independently an integer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound or the pharmaceutically acceptable salt thereof is administered to the patient by subcutaneous administration.

### Claim 3 (depends on 2)

The method of claim 2, wherein the subcutaneous administration is with a pen injector.

### Claim 4 (depends on 2)

The method of claim 2, wherein the subcutaneous administration is with a syringe and needle.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound or the pharmaceutically acceptable salt thereof is administered at intervals of at least 24 hours.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound or the pharmaceutically acceptable salt thereof is administered at intervals of one week.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound 31 is formed by reaction of the compound of formula 30:
with PEG 2×10 kDa maleimide.

### Claim 8

A method of parathyroid hormone replacement therapy, comprising administering a compound according to formula 31:
or a pharmaceutically acceptable salt thereof to a patient in need of the therapy, thereby alleviating symptoms relating to hypocalcemia, hypercalciuria, and hyperphosphatemia, without causing hypercalcemia,
wherein PTH(1-34) is parathyroid hormone of the amino acid sequence SEQ ID NO:51, Nαs1 is the alpha amino group of the N-terminal serine of SEQ ID NO:51 and 2×10 kDa PEG comprises a branched polyethylene glycol polymer of two arms in which each arm has a molecular weight of about 10 kDa and is a moiety of formula (b)
wherein the dashed line indicates attachment to —S— in compound 31, and each of m and p of each moiety is independently an integer.

### Claim 9 (depends on 8)

The method of claim 8, wherein the compound 31 is formed by reaction of the compound of formula 30:
with PEG 2×10 kDa maleimide.