Delivery of therapeutic agents by a collagen binding protein

Patent metadata

Field	Value
Publication number	US-11001820-B2
Application number	US-201715407589-A
Country	US
Kind code	B2
Filing date	Jan 17, 2017
Priority date	Dec 14, 2011
Publication date	May 11, 2021
Grant date	May 11, 2021

Abstract

Methods of delivering therapeutic agents by administering compositions including a bacterial collagen-binding polypeptide segment linked to the therapeutic agent to subjects in need of treatment with the therapeutic agent are provided. In these methods, the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist, basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). The bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen. Methods of treating collagenopathies using a composition including a collagen-binding polypeptide and a PTH/PTHrP receptor agonist are also provided. In addition, methods of treating hyperparathyroidism, and hair loss using compositions comprising a collagen binding polypeptide and a PTH/PTHrP receptor agonist are provided. Finally, methods of reducing hair regrowth by administering a composition including a collagen binding polypeptide and a PTH/PTHrP receptor antagonist are provided.

First claim

We claim:

1. A method of delivering a therapeutic agent comprising:
(a) selecting a subject in need of treatment for a disease selected from the group consisting of osteogenesis imperfecta, Stickler's syndrome, Ehlers-Danlos syndrome, Alport's syndrome, and Caffey's disease, and
(b) administering a composition comprising a bacterial collagen-binding polypeptide segment linked to a therapeutic agent to the subject,
wherein the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist, and
wherein the bacterial collagen-binding polypeptide segment binds to sites of partially untwisted or under-twisted collagen and delivers the agent thereto, and
wherein the bacterial collagen-binding polypeptide segment comprises a collagen-binding polypeptide derived from an M9 peptidase selected from the group consisting of Clostridium, Bacillus and Vibrio , one of SEQ ID NOs: 6, 13-34, a fragment of at least 8 consecutive amino acids of one of SEQ ID NOs: 6, 13-34, residues 34-158 of SEQ ID NO: 1, a fragment of at least 8 consecutive amino acids from residues 34-158 of SEQ ID NO: 1, a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1, and a peptide that is at least 90% identical to one of SEQ ID NOs: 13-34.

2. The method of claim 1 , wherein the therapeutic agent is an agent capable of promoting bone growth, decreasing inflammation, or promoting collagen stability.

3. The method of claim 1 , wherein the therapeutic agent is selected from the group consisting of BMP-2, BMP-3, FGF-2, FGF-4, anti-sclerostin antibody, growth hormone, IGF-1, VEGF, TGF-β, KGF, FGF-10, TGF-α, TGF-β1, TGF-β receptor, GM-CSF, EGF, PDGF and connective tissue growth factors.

4. The method of claim 1 , wherein the bacterial collagen-binding polypeptide segment comprises a collagen-binding polypeptide selected from the group consisting of residues 34-158 of SEQ ID NO: 1, a fragment of at least 8 consecutive amino acids from residues 34-158 of SEQ ID NO: 1, and a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1.

5. The method of claim 1 , wherein the collagen-binding polypeptide segment and the therapeutic agent are chemically cross-linked to each other or are polypeptide portions of a fusion protein.

6. The method of claim 1 , wherein the therapeutic agent is a polypeptide and the N-terminus of the collagen-binding polypeptide segment is linked directly or through a linker polypeptide segment to the C-terminus of the therapeutic agent polypeptide.

7. The method of claim 1 , wherein the composition has at least 50% greater activity in the subject than the therapeutic agent administered alone.

8. The method of claim 1 , wherein the composition is administered intramuscularly, intradermally, intravenously, subcutaneously, intraperitoneally, topically, orally, parenteral, or intranasally.

9. The method of claim 1 , wherein the subject is a human.

10. The method of claim 1 , wherein the composition is administered in aqueous solution at pH below about 5.0 or above about 6.0.

11. The method of claim 6 , wherein the linker polypeptide includes a polycystic kidney disease (PKD) domain of the collagen-binding protein.

12. The method of claim 11 , wherein the PKD domain comprises residues 807-901 of SEQ ID NO: 6.

13. The method of claim 1 , wherein the collagen-binding polypeptide includes residues 894-1008, 894-1021, 901-1021, or 901-1008 of SEQ ID NO: 6 or a homolog thereof.

14. The method of claim 6 , wherein collagen binding polypeptide include residues 37-251 of SEQ ID NO: 2 or residues 807-1021 of SEQ ID NO: 6.

15. The method of claim 1 , wherein the collagen binding polypeptide comprises residues 34-158 of SEQ ID NO: 1.

16. The method of claim 1 , wherein the collagen binding polypeptide comprises a peptide that is at least 90% identical to one of SEQ ID NOs: 13-34.

17. The method of claim 1 , wherein the collagen binding polypeptide is a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1.

Assignees

• Univ Arkansas
• The Kitasato Inst
• Montefiore Med Center
• Univ Kagawa Nat Univ Corp

Inventors

• Ponnapakkam Tulasi
• Philominathan Sagaya Theresa Leena
• Sakon Joshua
• Katikaneni Ranjitha
• Koide Takaki
• Matsushita Osamu
• Gensure Robert C
• Nishi Nozomu

Classifications

• A61K38/193

  Colony stimulating factors [CSF] · CPC title

• C07K14/61

  Growth hormone [GH], i.e. somatotropin · CPC title

• A61K38/00

  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) · CPC title

• C12N9/52 Primary

  derived from bacteria {or Archaea} · CPC title

• A61Q7/00

  Preparations for affecting hair growth · CPC title