# US 2020/0399309 A1 · Therapeutic agents for reducing parathyroid hormone levels

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- Number: US 2020/0399309 A1
- Document ID: US20200399309A1
- Status: Published application
- Kind: A1
- Application number: 17/010,773
- Filed: 2020-09-02
- Published: 2020-12-24
- Earliest claimed: 2009-07-29
- Assignees: KAI Pharmaceuticals, Inc.
- Applicants: Kai Pharmaceuticals, Inc.
- Inventors: Felix Karim; Amos Baruch; Derek Maclean; Kanad Das; Qun Yin
- Web page: https://patentgrep.com/patent/US20200399309A1

## CPC

- C07K 7/06: having 5 to 11 amino acids
- 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 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/14: for calcium homeostasis (vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04)
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 5/18: of the parathyroid hormones
- A61P 5/20: for decreasing, blocking or antagonising the activity of PTH
- A61P 13/12: of the kidneys
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 5/1013: {the side chain containing O or S as heteroatoms, e.g. Cys, Ser}
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- 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)
- 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)
- 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

Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

## Claims

### Claim 1

A compound comprising the formula:
X1-X2-X3-X4-X5-X6-X7
wherein
X1 is an amino acid comprising a thiol-containing group, D-penicillamine, d-homocysteine or mercaptopropionic acid;
X2, X3, X4, X5, X5, and X7 are each D-arginine.

### Claim 2 (depends on 1)

The compound of claim 1, wherein X1 is an amino acid comprising a thiol-containing group is selected from L-cysteine and D-cysteine.

### Claim 3 (depends on 1, 2)

The compound of claim 1 or claim 2, wherein the compound is chemically modified at the N-terminus, the C-terminus or both.

### Claim 4 (depends on 1, 2, 3)

The compound of any one of claims 1-3, wherein the N-terminus of the compound is acetylated and the C-terminus of the peptide is amidated.

### Claim 5 (depends on 1, 2, 3, 4)

The compound of any one of claims 1-4, wherein the compound is Ac-crrrrrr-NH2 (SEQ ID NO: 6).

### Claim 6 (depends on 1, 2, 3, 4)

The compound of any one of claims 1-4, wherein the compound is Ac-beta alanine-rrrrrr-NH2 (SEQ ID NO: 30).

### Claim 7 (depends on 1, 2, 3, 4)

The compound of any one of claims 1-4, wherein the compound is mercaptopropionic acid-rrrrrr-NH2 (SEQ ID NO: 31).

### Claim 8 (depends on 1, 2, 3, 4)

The compound of any one of claims 1-4, wherein the compound is Ac-d-homocysteine-rrrrrr-NH2 (SEQ ID NO: 32).

### Claim 9 (depends on 1, 2, 3, 4)

The compound of any one of claims 1-4, wherein the compound is Ac-D-penicillamin-rrrrrr-NH2 (SEQ ID NO: 33).

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A composition comprising the compound of any one of claims 1-9 and a pharmaceutically acceptable excipient.

### Claim 11 (depends on 10)

A composition comprising a compound according to any one of claim 10, for use in the treatment of a subject suffering from hyperparathyroidism or a hypercalcemic disorder.