Matricryptic ECM peptides for tissue reconstruction

Patent metadata

Field	Value
Publication number	US-9340602-B2
Application number	US-201414248465-A
Country	US
Kind code	B2
Filing date	Apr 9, 2014
Priority date	Oct 9, 2009
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Chemoattractant polypeptide compounds for progenitor cells and compositions and drug products comprising the compounds are provided herein. Methods for attracting progenitor cells to a location in or on a patient also are provided along with methods of growing and repairing bone.

First claim

We claim:

1. A method of attracting progenitor cells to a location in a patient, comprising administering to a location in the patient one or more isolated and purified polypeptides that:
consist of or consist essentially of sequence IAG-R 1 -GR 2 -EK-R 3 -GG-R 4 , where R 1 is Ile or Val; R 2 is Gly or Ala, R 3 is Ser or Ala and R 4 is Phe or Tyr (SEQ ID NO: 3), e.g., IAGVGGEKSGGF (SEQ ID NO: 1); the sequence GPVGPSGPPGK (SEQ ID NO: 2); or the sequence GPVGPHGPPGK (SEQ ID NO: 7), or a pharmaceutically acceptable salt of thereof;
consist of or consist essentially of a sequence having 75% or greater identity with IAGVGGEKSGGF (SEQ ID NO: 1); a sequence having greater than 90% identity with GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt of thereof;
consist of or consist essentially one of the sequences IAGVGGEKSGGF (SEQ ID NO: 1) or GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt thereof; or consist of 12-50 amino acids comprising: the sequence IAG-R 1 -GR 2 -EK-R 3 -GG-R 4 , where R 1 is Ile or Val; R 2 is Gly or Ala, R 3 is Ser or Ala and R 4 is Phe or Tyr (SEQ ID NO: 3); a sequence having 75% or greater identity with IAGVGGEKSGGF (SEQ ID NO: 1); a sequence having greater than 90% identity with GPVGPSGPPGK (SEQ ID NO: 2); the sequence IAGVGGEKSGGF (SEQ ID NO: 1); the sequence GPVGPSGPPGK (SEQ ID NO: 2); or the sequence GPVGPHGPPGK (SEQ ID NO: 7), or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the one or more of the isolated and purified polypeptides:
consist of sequence IAG-R 1 -GR 2 -EK-R 3 -GG-R 4 , where R 1 is Ile or Val; R 2 is Gly or Ala, R 3 is Ser or Ala and R 4 is Phe or Tyr (SEQ ID NO: 3), e.g., IAGVGGEKSGGF (SEQ ID NO: 1); the sequence GPVGPSGPPGK (SEQ ID NO: 2); or the sequence GPVGPHGPPGK (SEQ ID NO: 7), or a pharmaceutically acceptable salt of thereof;
consist of a sequence having 75% or greater identity with IAGVGGEKSGGF (SEQ ID NO: 1); a sequence having greater than 90% identity with GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt of thereof; or
consist of one of the sequences IAGVGGEKSGGF (SEQ ID NO: 1) or GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt thereof thereby attracting progenitor cells to the location.

3. The method of claim 1 , comprising administering an isolated and purified polypeptide chosen from one or both of IAGVGGEKSGGF (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof, and GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt thereof to the location in the patient.

4. The method of claim 1 , wherein the polypeptide is administered in a concentration of at least 100 pM.

5. The method of claim 4 , wherein the polypeptide is administered in a concentration of between about 10 pM and 100 μM.

6. The method of claim 4 , wherein the polypeptide is administered in a concentration of between about 10 pM and less than or equal to about 10-50 μM.

7. The method of claim 1 , in which the progenitor cells are osteogenic.

8. The method of claim 1 , in which the isolated and purified polypeptide consists of 12-50 amino acids comprising: the sequence IAG-R 1 -GR 2 -EK-R 3 -GG-R 4 , where R 1 is Ile or Val; R 2 is Gly or Ala, R 3 is Ser or Ala and R 4 is Phe or Tyr (SEQ ID NO: 3); a sequence having 75% or greater identity with IAGVGGEKSGGF (SEQ ID NO: 1); the sequence IAGVGGEKSGGF (SEQ ID NO: 1); or the sequence GPVGPSGPPGK (SEQ ID NO: 2), or pharmaceutical salts thereof.

9. The method of claim 8 , wherein the one or more of the isolated and purified polypeptides:
consist of sequence IAG-R 1 -GR 2 -EK-R 3 -GG-R 4 , where R 1 is Ile or Val; R 2 is Gly or Ala, R 3 is Ser or Ala and R 4 is Phe or Tyr (SEQ ID NO: 3), e.g., IAGVGGEKSGGF (SEQ ID NO: 1); the sequence GPVGPSGPPGK (SEQ ID NO: 2); or the sequence GPVGPHGPPGK (SEQ ID NO: 7), or a pharmaceutically acceptable salt of thereof;
consist of a sequence having 75% or greater identity with IAGVGGEKSGGF (SEQ ID NO: 1); a sequence having greater than 90% identity with GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt of thereof; or
consist of one of the sequences IAGVGGEKSGGF (SEQ ID NO: 1) or GPVGPSGPPGK (SEQ ID NO: 2), or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 , wherein the polypeptide is administered in a concentration of at least 100 pM.

11. The method of claim 10 , wherein the polypeptide is administered in a concentration of between about 10 pM and 100 μM.

12. The method of claim 10 , wherein the polypeptide is administered in a concentration of between about 10 pM and less than or equal to about 10-50 μM.

13. The method of claim 1 , in which the one or more isolated and purified polypeptides are administered at or adjacent to a bone injury or defect.

14. The method of claim 1 , in which the one or more isolated and purified polypeptides are administered in a biological scaffold.

15. The method of claim 1 , in which the one or more isolated and purified polypeptides are administered by a transdermal device.

Assignees

• Univ Pittsburgh—Of The Commonwealth System Of Higher Education
• Univ Pittsburgh

Inventors

• Agrawal Vineet
• Badylak Stephen F
• Johnson Scott A
• Tottey Stephen

Classifications

• A61P19/10

  for osteoporosis · CPC title

• A61K35/22

  Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland · CPC title

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · 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

• A61P19/00

  Drugs for skeletal disorders · CPC title