# US 11,992,496 B1 · Oral testosterone therapy

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- Number: US 11,992,496 B1
- Document ID: US11992496B1
- Status: Granted
- Kind: B1
- Application number: 18/310,784
- Filed: 2023-05-02
- Granted: 2024-05-28
- Earliest claimed: 2016-11-30
- Applicants: Lipocine Inc.
- Inventors: Nachiappan Chidambaram; Satish K. Nachaegari; Mahesh V. Patel; Kilyoung Kim
- Web page: https://patentgrep.com/patent/US11992496B1

## CPC

- A61K 31/568: substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61P 5/24: of the sex hormones
- A61K 9/4858: {Organic compounds}
- 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

Disclosed are methods and compositions for testosterone replacement therapy, especially for use in administration to hypogonadal males. The methods and compositions employ an untitrated dose dosing regimen that does not require titration or dose adjustments and that can provide a therapeutically effective amount of a testosterone ester, such as a non-undecanoate testosterone ester, while avoiding unacceptably high testosterone levels.

## Claims

### Claim 1

A method of treating a subject having a condition associated with at least one of fatigue, a reduction in muscle size, and a reduction in muscle strength, said method comprising orally administering a pharmaceutical composition comprising a therapeutically effective amount of a non-undecanoate testosterone ester in an untitrated dose administration regimen with food.

### Claim 2 (depends on 1)

The method of claim 1, wherein said composition further comprises an additive.

### Claim 3 (depends on 1)

The method of claim 1, wherein said untitrated dose administration regimen provides a total daily dose of said non-undecanoate testosterone ester of at least one of a minimum of about 375 mg, a maximum of about 1150 mg, 375-1150 mg, 750-1150 mg, 800-1100 mg, 850-1050 mg, 900-1100 mg, 925-1075 mg, 950-1050 mg, 975-1025 mg, 985-1015 mg, 990-1010 mg, 995-1005 mg, about 750 mg, and about 1000 mg.

### Claim 4 (depends on 1)

The method of claim 1, wherein said untitrated dose administration regimen comprises administering said composition at least once daily.

### Claim 5 (depends on 1)

The method of claim 1, wherein said composition is in a form of at least one of a hard capsule, a soft capsule, a tablet, a caplet, a powder, a granulate, a particulate, a bead, a pellet, a sprinkle, a suspension, a solution, and a combination thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein a unit dosage form of said composition comprises about 100-500 mg of said non-undecanoate testosterone ester.

### Claim 7 (depends on 1)

The method of claim 1, further comprising measuring a therapy discontinuation criterion that indicates an advised discontinuation of therapy where serum testosterone (T) levels are consistently >2500 ng/dl.

### Claim 8 (depends on 1)

The method of claim 1, wherein said food comprises food having a fat content of at least one of at least 10 g, at least 15 g, at least 20 g, at least 30 g, and about 10-60 g.

### Claim 9 (depends on 1)

The method of claim 1, wherein said composition is administered to at least one of a eugonadal subject and a hypogonadal subject, and wherein said method causes daily average serum testosterone (Cavg) to be in a normal eugonadal range in at least 75% of subjects in a population having said condition.

### Claim 10

A method of treatment comprising orally administering with food at least one of:
an untitrated dose of about 100-500 mg of a non-undecanoate testosterone ester in an untitrated dose dosing regimen, and
a total daily dose of at least about 500 mg of a non-undecanoate testosterone ester in an untitrated dose dosing regimen.

### Claim 11 (depends on 10)

The method of claim 10, wherein said composition further comprises an additive.

### Claim 12 (depends on 10)

The method of claim 10, wherein said untitrated dose administration regimen provides a total daily dose of said non-undecanoate testosterone ester of at least one of a minimum of about 375 mg, a maximum of about 1150 mg, 375-1150 mg, 750-1150 mg, 800-1100 mg, 850-1050 mg, 900-1100 mg, 925-1075 mg, 950-1050 mg, 975-1025 mg, 985-1015 mg, 990-1010 mg, 995-1005 mg, about 750 mg, and about 1000 mg.

### Claim 13 (depends on 10)

The method of claim 10, wherein said untitrated dose administration regimen comprises administering said composition at least once daily.

### Claim 14 (depends on 10)

The method of claim 10, wherein said composition is in a form of at least one of a hard capsule, a soft capsule, a tablet, a caplet, a powder, a granulate, a particulate, a bead, a pellet, a sprinkle, a suspension, a solution, and a combination thereof.

### Claim 15 (depends on 10)

The method of claim 10, wherein a unit dosage form of said composition comprises about 100-500 mg of said non-undecanoate testosterone ester.

### Claim 16 (depends on 10)

The method of claim 10, further comprising measuring a therapy discontinuation criterion that indicates an advised discontinuation of therapy where serum testosterone (T) levels are consistently >2500 ng/dl.

### Claim 17 (depends on 10)

The method of claim 10, wherein said food comprises food having a fat content of at least one of at least 10 g, at least 15 g, at least 20 g, at least 30 g, and about 10-60 g.

### Claim 18 (depends on 10)

The method of claim 10, wherein said composition is administered to at least one of a eugonadal subject and a hypogonadal subject, and wherein said method causes daily average serum testosterone (Cavg) to be in a normal eugonadal range in at least 75% of subjects in a population having a condition associated with at least one of fatigue, a reduction in muscle size, and a reduction in muscle strength.

### Claim 19

A pharmaceutical composition comprising (i) a therapeutically effective amount of a non-undecanoate testosterone ester; (ii) at least one pharmaceutically acceptable carrier; and (iii) at least one additive, wherein said non-undecanoate testosterone ester comprises about 15%-45% w/w of said composition, wherein administration of said composition to a subject having a condition associated with at least one of fatigue, a reduction in muscle size, and a reduction in muscle strength, results in improving or preventing further worsening of said at least one of fatigue, said reduction in muscle size and said reduction in muscle strength.

### Claim 20 (depends on 19)

The composition of claim 19, wherein said composition comprises at least one of a lipophilic surfactant, a hydrophilic surfactant, a solidifying agent, a fatty acid, and a combination thereof.

### Claim 21 (depends on 20)

The composition of claim 20, wherein said lipophilic surfactant comprises at least one of a monoglyceride, a diglyceride, a triglyceride, and a combination thereof, and wherein said hydrophilic surfactant comprises at least one of a PEG-8 caprylic/capric glyceride, a lauroyl macrogol-32 glyceride, a stearoyl macrogol glyceride, a PEG-40 hydrogenated castor oil, a PEG-35 hydrogenated castor oil, a sodium lauryl sulfate, a sodium dioctyl sulfosuccinate, a polyethylene glycol fatty acid mono-ester mixture, a polyethylene glycol fatty acid di-ester mixture, a polysorbate 80, a polysorbate 20, a polyethylene glycol 1000 tocopherol succinate, a phytosterol, a phytosterol fatty acid ester, a lanosterol PEG-24 cholesterol ether, a PEG-30 soya sterol, a PEG-25 phyto sterol, a PEG-30 cholestanol, and a combination thereof, and wherein said solidifying agent comprises at least one of polyethylene glycol, sorbitol, gelatin, stearic acid, cetyl alcohol, cetosterayl alcohol, paraffin wax, bees wax, microcrystalline wax, polyvinyl alcohol, glyceryl stearate, glyceryl distearate, glyceryl monostearate, glyceryl palmitostearate, glyceryl behenate, hydrogenated castor oil, hydrogenated vegetable oil, a vitamin E derivative, sterol; phytosterol, a phytosterol fatty acid ester, and cholesterol, and a combination thereof, and wherein said fatty acid comprises at least one of a monoglyceride, a diglyceride, a triglyceride, and a combination thereof.

### Claim 22 (depends on 19)

The composition of claim 19, wherein said composition further comprises an additive.

### Claim 23 (depends on 19)

The composition of claim 19, wherein said composition comprises an untitrated dose administration regimen composition.

### Claim 24 (depends on 19)

The composition of claim 19, wherein said administration composition provides a total daily dose of said non-undecanoate testosterone ester of at least one of a minimum of about 375 mg, a maximum of about 1150 mg, 375-1150 mg, 750-1150 mg, 800-1100 mg, 850-1050 mg, 900-1100 mg, 925-1075 mg, 950-1050 mg, 975-1025 mg, 985-1015 mg, 990-1010 mg, 995-1005 mg, about 750 mg, and about 1000 mg.

### Claim 25 (depends on 19)

The composition of claim 19, wherein said composition comprises an at least once daily administration composition.

### Claim 26 (depends on 19)

The composition of claim 19, wherein said composition comprises a form of at least one of a hard capsule, a soft capsule, a tablet, a caplet, a powder, a granulate, a particulate, a bead, a pellet, a sprinkle, a suspension, a solution, and a combination thereof.

### Claim 27 (depends on 19)

The composition of claim 19, wherein a unit dosage form of said composition comprises about 100-500 mg of said non-undecanoate testosterone ester.

### Claim 28 (depends on 19)

The composition of claim 19, wherein said composition includes a discontinuation criterion that indicates an advised discontinuation of administration of said composition where serum testosterone (T) levels are consistently >2500 ng/dl.

### Claim 29 (depends on 19)

The composition of claim 19, wherein said composition comprises at least one of an administration with food composition and an administration without food composition, and wherein said food comprises food having a fat content of at least one of at least 10 g, at least 15 g, at least 20 g, at least 30 g, and about 10-60 g.

### Claim 30 (depends on 19)

The composition of claim 19, wherein said composition comprises an administration to at least one of a eugonadal subject and a hypogonadal subject composition, and wherein said administration causes daily average serum testosterone (Cavg) to be in a normal eugonadal range in at least 75% of subjects in a population having said condition.