Delivery of therapeutic agents by a collagen binding protein

Patent metadata

Field	Value
Publication number	US-9579273-B2
Application number	US-201214365226-A
Country	US
Kind code	B2
Filing date	Dec 14, 2012
Priority date	Dec 14, 2011
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

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 treating a subject having alopecia that is not chemotherapy-induced comprising administering a composition comprising a bacterial collagen-binding polypeptide segment linked to a PTH/PTHrP receptor agonist to the subject to increase hair growth in the subject in need thereof for treatment of alopecia that is not chemotherapy-induced, wherein the bacterial collagen-binding polypeptide segment comprises a collagen-binding polypeptide derived from an M9 peptidase from Clostridium, Bacillus and Vibrio selected from the group consisting of one of SEQ ID NOs: 13-34 or a fragment of at least 8 consecutive amino acids of SEQ ID NOs: 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, or a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1 or SEQ ID NOs: 13-34 and wherein the PTH/PTHrP receptor agonist comprises residues 1-33 of SEQ ID NO: 1, PTH (SEQ ID NO: 7), residues 1-14 of SEQ ID NO: 1, residues 1-34 of SEQ ID NO: 7 or a fragment of at least 8 consecutive amino acids from residues 1-34 of SEQ ID NO: 7.

2. The method of claim 1 , wherein the alopecia is alopecia areata or is related to male pattern baldness or polycystic ovarian syndrome.

3. The method of claim 1 , wherein the composition is administered locally.

4. The method of claim 3 , wherein the composition is administered topically.

5. The method of claim 1 , wherein the PTH/PTHrP receptor agonist 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 PTH/PTHrP receptor agonist polypeptide or 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 subject is a human.

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

8. The method of claim 1 , wherein the bacterial collagen-binding polypeptide segment comprises one of SEQ ID NOs: 13-34, residues 34-158 of SEQ ID NO: 1, or a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1 or SEQ ID NOs: 13-34.

9. The method of claim 1 , wherein the PTH/PTHrP receptor agonist comprises residues 1-33 of SEQ ID NO: 1, PTH (SEQ ID NO: 7), residues 1-14 of SEQ ID NO: 1, residues 1-34 of SEQ ID NO: 7.

10. The method of claim 1 , wherein the bacterial collagen-binding polypeptide segment linked to the PTH/PTHrP receptor agonist is a fusion protein comprising SEQ ID NO: 1.

11. The method of claim 1 , wherein the bacterial collagen-binding polypeptide segment linked to the PTH/PTHrP receptor agonist is a fusion protein comprising SEQ ID NO: 2.

12. The method of claim 1 , wherein the collagen-binding polypeptide segment further comprises residues 807-900 of SEQ ID NO: 6.

Assignees

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

Inventors

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

Classifications

• A61P5/18

  of the parathyroid hormones · CPC title

• A61P5/20

  for decreasing, blocking or antagonising the activity of PTH · CPC title

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title