Myostatin Inhibitor Comprising Extracellular Water-Soluble Domains of DLK1 As Active Ingredient

• US 20150030595A1
• Filed: 01/03/2013
• Published: 01/29/2015
• Est. Priority Date: 01/05/2012
• Status: Active Grant

• Current Assignee: Antibody and Receptor Therapeutics Co., Ltd.
• Original Assignee: Antibody and Receptor Therapeutics Co., Ltd.
• Inventors: Lee, Dong Hee, Jang, Myeong Hee, Park, Bum Chan, Park, Jae Eun, Yoo, Seok Ho, Kim, Hye Nan
• Granted Patent: US 9,388,223 B2
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/06 Anabolic agents androgens A61P5/26
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention relates to a myostatin inhibitor comprising extracellular water-soluble domains of delta-like 1 homolog (DLK1) as active ingredients. More particularly, the present invention relates to a composition for inhibiting myostatin activity, comprising, as active ingredients, extracellular water-soluble domains of DLK1 or a deletion mutant of extracellular water-soluble domains of DLK1. The myostatin inhibitor of the present invention is bonded to the myostatin or activin receptor type IIB so as to inhibit the action mechanism of the myostatin, to thereby promote myogenesis and prevent differentiation into fat cells. Therefore, the myostatin inhibitor of the present invention may be used in preventing and treating diseases such as muscular dysplasia that requires differentiation to muscular cells, or metabolic diseases.

Claims

1. A method for treating a myostatin-related disease, comprising administering an extracellular water-soluble domain of a delta-like 1 homolog (DLK1), a fragment of the extracellular water-soluble domain of DLK1, a mutant of the extracellular water-soluble domain of DLK1, or a fragment of the mutant as an active ingredient.

2. The method of claim 1, wherein the extracellular water-soluble domain of DLK1 consists of an amino acid sequence set forth in SEQ ID NO:

29.

3. The method of claim 1, wherein the mutant of the extracellular water-soluble domain of DLK1 is a deletion mutant of the extracellular water-soluble domain of DLK1.

4. The method of claim 3, wherein the deletion mutant of the extracellular water-soluble domain of DLK1 is a deletion mutant including an epidermal growth factor-like repeat (EGF-like repeat), or a juxtamembrane sequence.

5. The method of claim 3, wherein the deletion mutant of the extracellular water-soluble domain of DLK1 has one of amino acid sequences set forth in SEQ ID NO:

30 to SEQ ID NO;

34.

6. The method of claim 1, wherein the extracellular water-soluble domain of DLK1, the fragment of the extracellular water-soluble domain of DLK1, the mutant of the extracellular water-soluble domain of DLK1, or the fragment of the mutant binds to a myostatin or activin receptor type IIB (ACVR2B) to inhibit the action of myostatin.

7. The method of claim 1, wherein the extracellular water-soluble domain of DLK1 or a fragment thereof is conjugated to a human antibody Fc region.

8. The method of claim 1, wherein, the myostatin-related disease is at least one selected from the group consisting of a muscle wasting disease, a metabolic disease, a degenerative bone disease, hypogonadism, and cachexia.

9. The method of claim 8, wherein the muscle wasting disease is at least one selected from the group consisting of muscular dystrophy, a rigid spine syndrome, a muscle-eye-brain disease, amyotrophic lateral sclerosis (a Lou Gehrig'"'"'s disease), a Charcot-Marie-Tooth disease, chronic inflammatory neuropathy, and distal myopathy.

10. The method of claim 8, wherein the metabolic disease is at least one selected from the group consisting of type 2 diabetes, noninsulin-dependent diabetes mellitus, hyperglycemia, obesity, and diabetic complications.

11. The method of claim 8, wherein the degenerative bone disease is osteoporosis.

12. A kit for diagnosing a myostatin-related disease, comprising an antibody or an aptamer specifically binding to DLK1-myostatin, DLK1-ACVR2B or a soluble fragment thereof.

13. The kit of claim 12, wherein the kit is an enzyme-linked immunosorbent assay (ELISA) kit, or a sandwich ELISA kit.

14-20. -20. (canceled)