# US 10,307,415 B2 · Epimorphic regeneration and related hydrogel delivery systems

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- Number: US 10,307,415 B2
- Document ID: US10307415B2
- Status: Granted
- Kind: B2
- Application number: 15/618,715
- Filed: 2017-06-09
- Published: 2017-09-28
- Granted: 2019-06-04
- Earliest claimed: 2013-11-13
- Assignees: Northwestern University; The Wistar Institute of Anatomy and Biology
- Applicants: Northwestern University; The Wistar Institute of Anatomy and Biology
- Inventors: Phillip B. Messersmith; Iossif A. Strehin; Ellen Heber-Katz
- Web page: https://patentgrep.com/patent/US10307415B2

## CPC

- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- C08G 65/332: containing carboxyl groups, or halides, or esters thereof
- C08G 65/333: containing nitrogen
- C08G 65/33331: {containing imide group}
- C08G 65/33337: {cyclic}
- C08G 65/33396: {having oxygen in addition to nitrogen}
- C08G 65/3342: {having sulfur bound to carbon and hydrogen}
- C08G 65/3344: {containing oxygen in addition to sulfur}
- C08G 65/3348: {containing nitrogen in addition to sulfur}
- C12N 9/0071: {acting on paired donors with incorporation of molecular oxygen (1.14)}
- C08G 2210/00: Compositions for preparing hydrogels
- C08G 2650/32: dendritic or similar
- C08G 2650/58: Ethylene oxide or propylene oxide copolymers, e.g. pluronics
- C08L 2203/02: for biomedical use
- C12Y 114/11002: Procollagen-proline dioxygenase (1.14.11.2), i.e. proline-hydroxylase
- 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)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- C12Y: ENZYMES

## Abstract

Methods and compositions are described for enhancing tissue regeneration or wound repair in a mammalian subject comprising a composition comprising (a) a proline hydroxylase inhibitor component or molecule that increases or upregulates HIF1a and (b) a carrier component comprising a hydrogel.

## Claims

### Claim 1

A method of modulating proline hydroxylase activity, said method comprising:
providing a composition comprising a prodrug of 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), said prodrug comprising a 1,4-DPCA component coupled to a cleavable polymer component, and a carrier component comprising a hydrogel comprising a chemical ligation product of
and wherein each of R1 and R2 is independently selected from hexaglycolic and tripentaerythritolic moieties, each of n1 and n2 is an integer independently selected from 1 to about 201, and Cys is an N-terminal cysteine residue; and
contacting said 1,4-DPCA component of said prodrug with a cellular medium expressing a proline hydroxylase, said cellular medium within a non-regenerative mammal presenting a tissue injury, said 1,4-DPCA component in an amount sufficient to modulate proline hydroxylase activity in said cellular medium and thereby induce a regenerative response.

### Claim 2 (depends on 1)

The method of claim 1 wherein said contact comprises administration of said composition, said administration selected from oral intake and subcutaneous, intramuscular, intravenous and intraperitoneal injection.

### Claim 3 (depends on 2)

The method of claim 2 wherein said administration comprises multiple doses over time.

### Claim 4 (depends on 2)

The method of claim 2 wherein said administration is at a site distal to said tissue injury.