# US 9,872,874 B2 · Dosage regimen for sapacitabine and seliciclib

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- Number: US 9,872,874 B2
- Document ID: US9872874B2
- Status: Granted
- Kind: B2
- Application number: 14/401,357
- Filed: 2013-05-14
- Published: 2015-06-18
- Granted: 2018-01-23
- Earliest claimed: 2012-05-15
- Assignees: Cyclacel Limited
- Applicants: Cyclacel Limited
- Inventors: Judy H. Chiao; David Blake; Daniella Zheleva; Susan Davis; Simon Green; Geoffrey Shapiro
- Web page: https://patentgrep.com/patent/US9872874B2

## CPC

- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/52: Purines, e.g. adenine
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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

A first aspect of the invention relates to a method of treating a proliferative disorder in a subject, said method comprising administering to the subject a therapeutically effective amount of (i) sapacitabine, or a metabolite thereof; and (ii) seliciclib; in accordance with a dosing regimen comprising at least one first treatment cycle and at least one second treatment cycle, wherein said first treatment cycle comprises: (a) administering a therapeutically effective amount of sapacitabine, or a metabolite thereof, for 3 to 5 consecutive days for 2 weeks, starting on day d, where d is the first day of treatment with sapacitabine, or the metabolite thereof, in said first treatment cycle; and (b) optionally administering a therapeutically effective amount of seliciclib for 3 to 5 consecutive days for 2 weeks, starting on day (d−1) relative to the administration of sapacitabine or the metabolite thereof, in said first treatment cycle; followed by a rest period of at least 2 weeks, or until treatment-related toxicities are resolved, whichever is longer; and wherein said second treatment cycle comprises: (a) administering a therapeutically effective amount of sapacitabine, or a metabolite thereof, for 3 to 5 consecutive days for 2 weeks, starting on day d, where d is the first day of treatment with sapacitabine, or the metabolite thereof, in said second treatment cycle; and (b) administering a therapeutically effective amount of seliciclib for 3 to 5 consecutive days for 2 weeks, starting on day (d−1) relative to the administration of sapacitabine or the metabolite thereof, in said second treatment cycle; followed by a rest period of at least 2 weeks, or until treatment-related toxicities are resolved, whichever is longer. Further aspects of the invention relate to a kit of parts, and corresponding uses.

## Claims

### Claim 1

A method of treating a proliferative disorder in a subject, wherein the proliferative disorder is a solid tumour selected from the group consisting of breast cancer, ovarian cancer, and pancreatic cancer, said method comprising administering to the subject a therapeutically effective amount of (i) sapacitabine, or a metabolite thereof, wherein the metabolite is 1-(-C-Cyano-2-deoxy-β-D-arabino-pentafuranosyl)-cytosine (CNDAC); and (ii) seliciclib; in accordance with a dosing regimen comprising at least one treatment cycle, wherein said treatment cycle comprises:
(a) administering sapacitabine, or metabolite thereof, twice a day in a dosage of from about 50 to about 300 mg per dose, for 7 consecutive days; and
(b) administering seliciclib twice a day in a dosage of from about 200 to about 1200 mg per dose for 3 consecutive days;
followed by a rest period of at least 10 days, or until treatment-related toxicities are resolved, whichever is longer,
wherein the seliciclib administered in step (b) is administered after the sapacitabine, or metabolite thereof, in step (a) without a rest period.

### Claim 2 (depends on 1)

A method according to claim 1 wherein the seliciclib administration starts the day after the sapacitabine administration has been completed.

### Claim 3 (depends on 1)

A method according to claim 1 wherein the treatment cycle is 21 days in length.

### Claim 4 (depends on 1)

A method according to claim 1 wherein the treatment cycle comprises:
(a) administering the sapacitabine, or metabolite thereof, for 7 consecutive days; followed by
(b) administering the seliciclib for 3 consecutive days;
followed by a rest period of 11 days.

### Claim 5 (depends on 1)

A method according to claim 1 wherein the treatment cycle is repeated two or more times.

### Claim 6 (depends on 1)

A method according to claim 1 wherein the sapacitabine is administered in an amount of about 50 mg twice daily (b.i.d.).

### Claim 7 (depends on 1)

A method according to claim 1 wherein the seliciclib is administered in an amount of about 200 mg to about 800 mg per dose.

### Claim 8 (depends on 1)

A method according to claim 1 wherein the seliciclib is administered in an amount of about 800 mg twice daily (b.i.d.).

### Claim 9 (depends on 1)

A method according to claim 1 wherein the sapacitabine is administered orally.

### Claim 10 (depends on 1)

A method according to claim 1 wherein the seliciclib is administered orally or intravenously.

### Claim 11 (depends on 1)

A method according to claim 1 wherein the cancer has a BRCA1 and/or a BRCA2 gene mutation.