# US 11,998,590 B2 · Use of Mullerian inhibiting substance (MIS) proteins for contraception and ovarian reserve preservation

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- Number: US 11,998,590 B2
- Document ID: US11998590B2
- Status: Granted
- Kind: B2
- Application number: 16/988,248
- Filed: 2020-08-07
- Published: 2020-12-03
- Granted: 2024-06-04
- Earliest claimed: 2013-12-11
- Assignees: The General Hospital Corporation
- Applicants: The General Hospital Corporation
- Inventors: Patricia K. Donahoe; David Pepin
- Web page: https://patentgrep.com/patent/US11998590B2

## CPC

- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- 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 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 15/18: Feminine contraceptives
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 2750/14142: virus or viral particle as vehicle, e.g. encapsulating small organic molecule
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2750/14171: Demonstrated in vivo effect
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

One aspect of the invention provides a method of contraception by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). The MIS can be produced endogenously in the subject by a vector, where the vector comprises a polynucletide encoding a recombinant MIS protein. In some embodiments, the contraception is permanent and only requires administration of the composition once. Another aspect of the invention relates to a method of preserving an ovarian reserve, the method comprising administering to a female subject a composition comprising MIS or an inducible vector that comprises a polynucleotide encoding a recombinant MIS protein.

## Claims

### Claim 1

A method of permanent contraception in a female cat comprising administering to the female cat an effective amount of a composition comprising a viral vector comprising one or more regulatory elements operatively linked to a nucleic acid encoding a wild-type Mullerian Inhibiting Substance (MIS) protein for permanent contraception in the female cat, wherein the effective amount of the composition administered to the female cat increases the concentration of MIS protein in the blood of the female cat to a MIS serum concentration of about 0.3 μg/ml to about 5 μg/ml.

### Claim 2 (depends on 1)

The method of claim 1, wherein the MIS protein is a wild-type feline MIS protein.

### Claim 3 (depends on 2)

The method of claim 2, wherein the viral vector is an AAV vector.

### Claim 4 (depends on 1)

The method of claim 1, wherein the viral vector is an adenoviral vector, an adeno-associated virus (AAV) vector, a poxvirus vector, or a lentiviral vector.

### Claim 5 (depends on 1)

The method of claim 1, wherein the viral vector is an AAV vector.

### Claim 6 (depends on 1)

The method of claim 1, wherein the one or more regulatory elements comprise a promoter element.

### Claim 7 (depends on 1)

The method of claim 1, wherein the one or more regulatory elements comprise a promoter element and an enhancer element.

### Claim 8 (depends on 1)

The method of claim 1, wherein the one or more regulatory elements comprise a constitutively active promoter.

### Claim 9 (depends on 1)

The method of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier.

### Claim 10 (depends on 1)

The method of claim 1, wherein the administering is a one-time injection.

### Claim 11 (depends on 1)

The method of claim 1, wherein the administering is via injection.

### Claim 12 (depends on 1)

The method of claim 1, wherein the administering is intravenous, subcutaneous, or intramuscular administration.

### Claim 13 (depends on 1)

The method of claim 1, wherein the administering is intramuscular administration.

### Claim 14

A method of arresting folliculogenesis in a female cat comprising administering to the female cat an effective amount of a composition comprising a viral vector comprising one or more regulatory elements operatively linked to a nucleic acid encoding a wild-type Mullerian Inhibiting Substance (MIS) protein, wherein folliculogenesis is arrested in the female cat, wherein the effective amount of the composition administered to the female cat increases the concentration of MIS protein in the blood of the female cat to a MIS serum concentration of about 0.3 μg/ml to about 5 μg/ml.

### Claim 15 (depends on 14)

The method of claim 14, wherein the MIS protein is a wild-type feline MIS protein.

### Claim 16 (depends on 14)

The method of claim 14, wherein the viral vector is an adenoviral vector, an adeno-associated virus (AAV) vector, a poxvirus vector, or a lentiviral vector.

### Claim 17 (depends on 15)

The method of claim 15, wherein the viral vector is an AAV vector.

### Claim 18 (depends on 14)

The method of claim 14, wherein the administering is a one-time injection.

### Claim 19 (depends on 14)

The method of claim 14, wherein the administering is intravenous, subcutaneous, or intramuscular administration.

### Claim 20

A method of permanent contraception in a female cat comprising administering to the female cat an effective amount of a composition comprising a viral vector comprising one or more regulatory elements operatively linked to a nucleic acid encoding a wild-type Mullerian Inhibiting Substance (MIS) protein for permanent contraception in the female cat, wherein the effective amount of the composition administered to the female cat increases the concentration of MIS protein in the blood of the female cat to a MIS serum concentration of about 0.3 μg/ml to about 1.5 μg/ml.

### Claim 21 (depends on 20)

The method of claim 20, wherein the MIS protein is a wild-type feline MIS protein.

### Claim 22 (depends on 20)

The method of claim 20, wherein the viral vector is an adenoviral vector, an adeno-associated virus (AAV) vector, a poxvirus vector, or a lentiviral vector.

### Claim 23 (depends on 20)

The method of claim 20, wherein the viral vector is an AAV vector.

### Claim 24 (depends on 20)

The method of claim 20, wherein the one or more regulatory elements comprise a promoter element.

### Claim 25 (depends on 20)

The method of claim 20, wherein the one or more regulatory elements comprise a promoter element and an enhancer element.

### Claim 26 (depends on 20)

The method of claim 20, wherein the one or more regulatory elements comprise a constitutively active promoter.

### Claim 27 (depends on 20)

The method of claim 20, wherein the composition further comprises a pharmaceutically acceptable carrier.

### Claim 28 (depends on 20)

The method of claim 20, wherein the administering is a one-time injection.

### Claim 29 (depends on 20)

The method of claim 20, wherein the administering is via injection.

### Claim 30 (depends on 20)

The method of claim 20, wherein the administering is intravenous, subcutaneous, or intramuscular administration.

### Claim 31 (depends on 20)

The method of claim 20, wherein the administering is intramuscular administration.