# US 11,299,724 B2 · Fusion protein, polynucleotide, genetic construct, producer, preparation for regeneration of cartilage

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- Number: US 11,299,724 B2
- Document ID: US11299724B2
- Status: Granted
- Kind: B2
- Application number: 16/316,254
- Filed: 2017-07-13
- Published: 2019-07-18
- Granted: 2022-04-12
- Earliest claimed: 2016-07-14
- Assignees: Limited Liability Company Biochemical Agent
- Applicants: Limited Liability Company Biochemical Agent
- Inventors: Ilya Vladimirovich Dukhovlinov; Ekaterina Alekseevna Fedorova
- Web page: https://patentgrep.com/patent/US11299724B2

## CPC

- C12N 9/6459: {t-plasminogen activator (3.4.21.68), i.e. tPA}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/475: Growth factors; Growth regulators
- C07K 14/485: Epidermal growth factor [EGF], i.e. urogastrone
- C07K 14/495: Transforming growth factor [TGF]
- C07K 14/50: Fibroblast growth factor [FGF]
- C07K 14/503: {basic FGF [bFGF]}
- C07K 14/65: Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- C07K 14/79: Transferrins, e.g. lactoferrins, ovotransferrins
- C12N 15/62: DNA sequences coding for fusion proteins
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/02: containing a signal sequence
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/70: containing domain for protein-protein interaction
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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

The invention relates to molecular biology, biotechnology, medicine, veterinary science. A group of inventions is proposed: a fusion protein comprising a ligand to MATN1 protein, and a growth factor of EGF, TGF, FGF, IGF, connected via a flexible link; such fusion protein further comprising the Fc-fragment of an antibody or a polypeptide binding with FcRn and/or transferrin or a fragment thereof, connected via a flexible link; encoding polynucleotide, a genetic construct for the synthesis of the fusion protein in producer cells, or cells of a target organism, the fusion protein producer, a producer of the genetic construct, a preparation for the regeneration of cartilage containing at least 1 fusion protein or genetic construct, for parenteral or, in the case of the preparation based on at least 1 fusion protein containing the transport domain, —oral administration, in the latter case the preparation is enclosed in an enteric coating.

## Claims

### Claim 1

A fusion protein comprising a ligand to matrilin (MATN1) set forth as the amino acid sequence of SEQ ID NO: 1 and a growth factor selected from the group consisting of Epidermal Growth Factor (EGF), Transforming Growth Factor (TGF), Fibroblast Growth Factor (FGF), and Insulin-like Growth Factor (IGF) set forth as the amino acid sequence of SEQ ID NO: 2, 3, 4 or 5, respectively, wherein the ligand to MATN1 and the growth factor are connected via a flexible linker set forth as the amino acid sequence of SEQ ID NO: 6.

### Claim 2 (depends on 1)

The fusion protein of claim 1, which is further connected via a flexible linker set forth as the amino acid sequence of SEQ ID NO: 6 to at least one of: (i) the Fc-fragment of an antibody set forth as the amino acid sequence of SEQ ID NO: 7 or a polypeptide which binds with FcRn set forth as the amino acid sequence of SEQ ID NO: 8, and (ii) transferrin set forth as the amino acid sequence of SEQ ID NO: 9 or a fragment thereof set forth as the amino acid sequence of SEQ ID NO: 10, wherein the connection between (i) and (ii) is also via the flexible linker.

### Claim 3 (depends on 1)

A preparation for regeneration of cartilage, containing at least one fusion protein of claim 1 as an active agent in an effective amount, and a physiologically acceptable carrier and a buffer solution, wherein the preparation is for parenteral administration.

### Claim 4 (depends on 2)

A preparation for regeneration of cartilage, containing at least one fusion protein of claim 2 as an active agent in an effective amount, and a physiologically acceptable carrier and a buffer solution, wherein the preparation is for parenteral administration.

### Claim 5 (depends on 2)

A preparation for regeneration of cartilage, containing at least one fusion protein of claim 2 as an active agent in an effective amount, and a physiologically acceptable carrier and a buffer solution, wherein the preparation is enclosed in an enteric coating for oral administration.

### Claim 6 (depends on 1)

A preparation for regeneration of cartilage containing:
as an active agent:
an effective amount of at least one fusion protein of claim 1; and
an effective amount of at least one fusion protein of claim 1 which is further connected via a flexible linker set forth as the amino acid sequence of SEQ ID NO: 6 to at least one of: (i) the Fc-fragment of an antibody set forth as the amino acid sequence of SEQ ID NO: 7 or a polypeptide which binds with FcRn set forth as the amino acid sequence of SEQ ID NO: 8, and (ii) transferrin set forth as the amino acid sequence of SEQ ID NO: 9 or a fragment thereof set forth as the amino acid sequence of SEQ ID NO: 10, wherein the connection of between (i) and (ii) is also via the flexible linker;
a physiologically acceptable carrier; and
a buffer solution,
wherein the preparation is for parenteral administration.