Mitigating tissue damage and fibrosis via latent transforming growth factor beta binding protein (LTBP4)

• US 9,873,739 B2
• Filed: 08/01/2013
• Issued: 01/23/2018
• Est. Priority Date: 08/01/2012
• Status: Active Grant

• Current Assignee: Ikaika Therapeutics, LLC
• Original Assignee: Ikaika Therapeutics, LLC
• Inventors: McNally, Elizabeth, Heydemann, Ahlke, Ceco, Ermelinda
• Primary Examiner(s): Gangle, Brian J
• Assistant Examiner(s): MCCOLLUM, ANDREA K
• Application Number:
  US13/957,100
• Publication Number:
  US 20140037637A1
• Time in Patent Office: 1,636 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/26 against hormones ; against hormone releasing or inhibiting factors
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

The disclosure relates to compositions and methods of mitigating tissue damage and fibrosis in a patient by modulating latent transforming growth factor beta binding protein (LTBP4)-induced proteolysis of a Transforming Growth Factor-beta (TGFβ) superfamily protein.

Claims

1. An isolated antibody that specifically binds to the sequence set forth in SEQ ID NO:

6.

2. A pharmaceutical formulation comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or diluent.

3. The formulation of claim 2, further comprising a second agent, wherein the second agent is selected from the group consisting of a modulator of an inflammatory response, a promoter of muscle growth, a chemotherapeutic agent and a modulator of fibrosis.

4. A kit comprising the antibody of claim 1, a pharmaceutically acceptable carrier or diluent, and instructions for use.

5. The kit of claim 4, further comprising a second agent, wherein the second agent is selected from the group consisting of a modulator of an inflammatory response, a promoter of muscle growth, a chemotherapeutic agent and a modulator of fibrosis.

6. A method of treating a patient having Duchenne Muscular Dystrophy, Limb Girdle Muscular Dystrophy, Becker Muscular Dystrophy, myopathy, pulmonary fibrosis, cardiomyopathy, acute lung injury, acute skeletal muscle injury, or acute myocardial injury, comprising administering the antibody of claim 1 to the patient.

7. The method of claim 6 further comprising administering a second agent, wherein the second agent is selected from the group consisting of a modulator of an inflammatory response, a promoter of muscle growth, a chemotherapeutic agent, and a modulator of fibrosis.

8. The method of claim 7 wherein the promoter of muscle growth is selected from the group consisting of insulin-like growth factor-1 (IGF-1), Akt/protein kinase B, clenbuterol, creatine, decorin, a steroid, and testosterone.

9. The method of claim 7 wherein the second agent is selected from the group consisting of an antibody to growth and differentiation factor-8 (GDF-8), an antibody to a GDF-8 receptor, a soluble GDF-8 receptor, a GDF-8 propeptide, follistatin, and a follistatin-domain-containing protein.

10. The method of claim 7 wherein the modulator of an inflammatory response is cyclosporin.

11. The method of claim 7 wherein the chemotherapeutic agent is selected from the group consisting of an alkylating agent, a nitrosourea, a ethylenimines/methylmelamine, an alkyl sulfonate, a triazine, an antimetabolite, a pyrimidine analog, a purine analog, an antimitotic drug, an epipodophylotoxin, an antibiotic, L-asparaginase, interferon-alpha, interleukin-2 (IL-2), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), cisplatin, carboplatin, en anthracenedione, substituted urea, a methylhydrazine derivative, an adrenocortical suppressant, an adrenocorticosteroid antagonist, progestin, estrogen, antiestrogen, an androgen, an antiandrogen, a gonadotropin-releasing hormone analog, and a non-steroidal antiandrogen.

12. The method of claim 7 wherein the modulator of fibrosis is selected from the group consisting of pirfenidone, an angiotensin-converting-enzyme (ACE) inhibitor, an angiotensin receptor blocker, and an aldosterone antagonist.