# US 11,304,962 B2 · Methods of reducing risk of preterm birth

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- Number: US 11,304,962 B2
- Document ID: US11304962B2
- Status: Granted
- Kind: B2
- Application number: 17/364,028
- Filed: 2021-06-30
- Published: 2021-10-21
- Granted: 2022-04-19
- Earliest claimed: 2015-04-30
- Assignees: Covis Pharma GmbH
- Applicants: COVIS Pharma GmbH
- Inventors: Robert Birch; Michael J. Jozwiakowski
- Web page: https://patentgrep.com/patent/US11304962B2

## CPC

- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- 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 31/57: substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- 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)

## Abstract

This disclosure generally relates to methods for reducing the risk of preterm birth in a pregnant human female patient that include subcutaneous administration of HPC. The disclosure relates in part to the discovery that subcutaneous administration of HPC is actually feasible and can result in sufficient plasma levels of HPC in pregnant patients that can reduce the risk of preterm birth.

## Claims

### Claim 1

A method of reducing the risk of preterm birth in a pregnant human patient, comprising: subcutaneously administering to the posterior portion of the upper arm of a pregnant human patient a 1.1 mL dose comprising a pharmaceutically acceptable non-aqueous formulation comprising 275 mg 17-α hydroxyprogesterone caproate,
wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient an AUC0-t of between about 120% to about 88% compared to an AUC0-t of the patient administered the same dosage amount of hydroxyprogesterone caproate intramuscularly, and
wherein the dose is administered weekly, beginning about 16 weeks or later of gestation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient an AUC0-t of about 104% compared to an AUC0-t of the patient administered the same dosage amount of hydroxyprogesterone caproate intramuscularly.

### Claim 3 (depends on 1)

The method of claim 1, wherein the dose is subcutaneously administered beginning between about 16 weeks, zero days of gestation to about 20 weeks, six days of gestation, and continued until about 37 weeks of gestation or until delivery, whichever occurs first.

### Claim 4 (depends on 1)

The method of claim 1, wherein the pregnant human patient has a singleton pregnancy.

### Claim 5 (depends on 4)

The method of claim 4, wherein the pregnant human patient has a history of singleton spontaneous preterm birth.

### Claim 6 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable non-aqueous liquid formulation further comprises castor oil.

### Claim 7 (depends on 6)

The method of claim 6, wherein the pharmaceutically acceptable non-aqueous liquid formulation further comprises benzyl benzoate.

### Claim 8 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable non-aqueous liquid formulation consists essentially of 17-α hydroxyprogesterone caproate, castor oil, and benzyl benzoate.

### Claim 9

A method of reducing the risk of preterm birth in a pregnant human patient, comprising: subcutaneously administering to the posterior portion of the upper arm of a pregnant human patient a 1.1 mL dose comprising a pharmaceutically acceptable non-aqueous formulation comprising 275 mg 17-α hydroxyprogesterone caproate,
wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient at least one of:
a Cmax of about between about 96% to about 157% compared to a Cmax of the patient administered the same dosage amount of hydroxyprogesterone caproate intramuscularly;
an AUC0-t of between about 120% to about 88% compared to an AUC0-t of the patient administered the same dosage amount of hydroxyprogesterone caproate intramuscularly;
a Cmax of about 8 ng/mL; and
an AUC of about 2,770 hr ·ng/mL to about 2,900 hr ng/mL, and wherein the dose is administered weekly, beginning about 16 weeks or later of gestation.

### Claim 10 (depends on 9)

The method of claim 9, wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient a Cmax of about between about 96% to about 157% compared to a Cmax of the patient administered the same dosage amount of hydroxyprogesterone caproate intramuscularly.

### Claim 11 (depends on 9)

The method of claim 9, wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient an AUC0-t of between about 120% to about 88% compared to an AUC0-t of the patient administered the same dosage amount of hydroxyprogesterone caproate intramuscularly.

### Claim 12 (depends on 9)

The method of claim 9, wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient a Cmax of about 8 ng/mL.

### Claim 13 (depends on 9)

The method of claim 9, wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient an AUC of about 2,770 hr ·ng/mL to about 2,900 hr ng/mL.

### Claim 14

A method of reducing the risk of preterm birth in a pregnant human patient, comprising: subcutaneously administering to the posterior portion of the upper arm of a pregnant human patient a 1.1 mL dose comprising a pharmaceutically acceptable non-aqueous formulation comprising 275 mg 17-α hydroxyprogesterone caproate,
wherein between about 24 to 48 hours after administration of the hydroxyprogesterone caproate dose the patient has a mean plasma concentration of about 5 ng/mL to about 12 ng/mL, and
wherein the dose is administered weekly, beginning about 16 weeks or later of gestation.

### Claim 15 (depends on 14)

The method of claim 14, wherein between about 24 to 48 hours after administration of the hydroxyprogesterone caproate dose the patient has a mean plasma concentration of between about 6 ng/mL to 8 ng/mL.

### Claim 16

A method of reducing the risk of preterm birth in a pregnant human patient, comprising: subcutaneously administering to the posterior portion of the upper arm of a pregnant human patient a 1.1 mL dose comprising a pharmaceutically acceptable non-aqueous formulation comprising 275 mg 17-α hydroxyprogesterone caproate,
wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient a Tmax of between about 18 hours to about 168 hours.

### Claim 17 (depends on 16)

The method of claim 16, wherein the subcutaneous administration of hydroxyprogesterone caproate provides in the patient a Tmax of about 24 hours.

### Claim 18 (depends on 1)

The method of claim 1, wherein the dosage is administered by a healthcare professional.

### Claim 19 (depends on 9)

The method of claim 9, wherein the dosage is administered by a healthcare professional.

### Claim 20 (depends on 14)

The method of claim 14, wherein the dosage is administered by a healthcare professional.

### Claim 21 (depends on 16)

The method of claim 16, wherein the dosage is administered by a healthcare professional.