# US 12,421,513 B2 · Compositions and methods for induced tissue regeneration in mammalian species

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- Number: US 12,421,513 B2
- Document ID: US12421513B2
- Status: Granted
- Kind: B2
- Application number: 17/177,747
- Filed: 2021-02-17
- Published: 2022-04-14
- Granted: 2025-09-23
- Earliest claimed: 2013-06-05
- Assignees: Reverse BioEngineering, Inc.
- Applicants: Reverse Bioengineering, Inc.
- Inventors: Michael D. West; Karen Chapman; Hal Sternberg
- Web page: https://patentgrep.com/patent/US12421513B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/715: Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/18: against material from animals or humans
- C12N 2310/14: interfering nucleic acids [NA]
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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)

## Abstract

Aspects of the present invention include methods and compositions related to the modulation of molecules regulating the regenerative potential of cells and tissues in the embryonic state and the loss thereof in later fetal and adult stages of development. Said methods and compositions have uses in research in stem cell biology and in increasing regenerative potential in fetal and adult tissues otherwise incapable of regeneration.

## Claims

### Claim 1

A method of increasing regenerative potential of mammalian connective tissue comprising administering to the one or more cells of the connective tissue a composition comprising a de-differentiation gene of OXTR and one or more de-differentiation genes selected from the group consisting of PCDHB2, PCDHB17, Nbla10527, RAB3IP, DLX1, DRD11P, FOXD1, LOC728755, AFF3, F2RL2, MN1, CBCAQH03 5′, LOC791120, SIX1, and WSB1,
wherein the administering the composition to the one or more cells of the connective tissue is ex vivo or in vitro, and
wherein one or more viral vectors comprise the OXTR gene and the one or more de-differentiation genes.

### Claim 2 (depends on 1)

The method of claim 1, wherein the connective tissue is from human.

### Claim 3 (depends on 1)

The method of claim 1, wherein the connective tissue is from an ear.

### Claim 4 (depends on 1)

The method of claim 1, wherein the connective tissue is from an endocrine gland, wherein the endocrine gland is selected from the group consisting of thyroid, parathyroid, adrenal, and endocrine portion of pancreas.

### Claim 5 (depends on 1)

The method of claim 1, wherein the connective tissue is from a bone, a skeletal muscle, a limb or a digit.

### Claim 6 (depends on 1)

The method of claim 1, wherein the connective tissue involves a hair follicle or an epithelial cell.

### Claim 7 (depends on 1)

The method of claim 1, wherein the one or more de-differentiation genes is SIX1.

### Claim 8 (depends on 1)

The method of claim 1, wherein the one or more viral vectors are a retroviral vector, a lentiviral vector, or an adenoviral vector.

### Claim 9 (depends on 1)

The method of claim 1, wherein the connective tissue is skin.

### Claim 10

A kit for enhancing regenerative potential of mammalian connective tissue, wherein the kit comprises a composition comprising a de-differentiation gene of OXTR and one or more de-differentiation genes selected from the group consisting of PCDHB2, PCDHB17, Nbla10527, RAB3IP, DLX1, DRD11P, FOXD1, LOC728755, AFF3, F2RL2, MN1, CBCAQH03 5′, LOC791120, SIX1, and WSB1, one or more viral vectors comprise the OXTR gene and the one or more de-differentiation genes.

### Claim 11 (depends on 10)

The kit of claim 10, further comprising one or more compounds that form a hydrogel.

### Claim 12 (depends on 11)

The kit of claim 11, wherein the one or more compounds that form the hydrogel comprises a monomer, polymer, initiating agent, cross-linking agent or any combination thereof.
