IP Library Granted Patent US 8,883,964
Granted Patent B2
US 8,883,964 · App. 13/605,534 · Granted Nov 11, 2014

Compositions comprising modified collagen and uses therefor

Inventors: Michael Yu (Timonium, MD); Jennifer H. Elisseeff (Baltimore, MD); Allen Yi-Lan Wang (Vienna, VA); Hyeseung Janice Lee (Washington, DC); Xiao Mo (Lutherville, MD)
Assignee: The Johns Hopkins University
A61K38/10A61K38/16
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Quick Facts
Patent No.
US 8,883,964
App. No.
13/605,534
Granted
Nov 11, 2014
Kind
B2
Abstract

The invention provides modified collagen and related therapeutic and diagnostic methods.

Claims (25)

1. A collagen mimetic peptide conjugate, wherein the peptide is an amino acid sequence selected from the group consisting of:

Gly 3 -(ProHypGly) 6 (SEQ ID NO: 13),

Gly 3 -(ProHypGly) 7 (SEQ ID NO: 14),

Gly 3 -(ProHypGly) 8 (SEQ ID NO: 15),

Gly 3 -(ProHypGly) 9 (SEQ ID NO: 16),

(ProHypGly) 6 -Tyr (SEQ ID NO: 17),

(ProHypGly) 7 -Tyr (SEQ ID NO: 18),

(ProHypGly) 8 -Tyr (SEQ ID NO: 19),

Cys-(Pro-Hyp-Gly) 3 (SEQ ID NO: 20),

Cys-(Pro-Hyp-Gly) 5 (SEQ ID NO: 21), and

Cys-(Pro-Hyp-Gly) 7 (SEQ ID NO: 22), and wherein the conjugate is selected from the group consisting of a cell adhesion molecule, a detectable label, a growth factor, a component of the extracellular matrix, a polymer, polyethylene glycol (PEG), and a small molecule.

2. The collagen mimetic peptide conjugate of claim 1 , wherein the peptide comprises: carboxyfluorescein-Gly 3 -(Pro-Hyp-Gly) 9 (SEQ ID NO: 23), carboxyfluorescein-Gly 3 -1ys-(Pro-Hyp-Gly) 8 (SEQ ID NO: 24), PEG 2000 -Gly 3 -(Pro-Hyp-Gly) 7 (SEQ ID NO: 25), Methoxy PEG 2000 -Gly 3 -(Pro-Hyp-Gly) 7 (SEQ ID NO: 6), (Pro-Hyp-Gly) 8 -Gly 3 -PEG 5000 -OH (SEQ ID NO: 26), [AcGly-Gly 2 -Lys-Gly 3 -(Pro-Hyp-Gly) 8 ] 4 -star shaped PEG (core sequence disclosed as SEQ ID NO: 27), [CF-Gly 3 -Lys-Gly 3 -(Pro-Hyp-Gly) 8 ] 4 -star shaped PEG (core sequence disclosed as SEQ ID NO: 28),

AcGly-Gly 2 -Lys-Gly 3 -(Pro-Hyp-Gly) 8 (SEQ ID NO: 29), FL-PEG 2000 -Gly 3 -(Pro-Hyp-Gly) 7 (SEQ ID NO: 30), and

5 carboxyfluorescein-Gly 3 (Pro-Hyp-Gly) 8 -Gly 3 -PEG 5000 -OH (SEQ ID NO: 31).

3. The collagen mimetic peptide conjugate of claim 1 , wherein the detectable label is 5-carboxy-fluorescein.

4. The collagen mimetic peptide conjugate of claim 1 , wherein the cell adhesion molecule is selected from the group consisting of a cadherin, fibronectin, integrin, laminin, and selectin.

5. The collagen mimetic peptide conjugate of claim 1 , wherein the detectable label is selected from the group consisting of a colloidal particle, an enzyme, an electron- dense reagent, a fluorescent dye, a hapten, an immunogen, a magnetic bead, and a radiolabel, gadolinium complex, gadodiamide derivative, ferric ammonium citrate, or mangafodipar trisodium.

6. The collagen mimetic peptide conjugate of claim 1 , wherein the growth factor promotes an activity selected from the group consisting of angiogenesis, cell growth, differentiation, proliferation, neurogenesis, osteogenesis, stem cell renewal, and cell survival.

7. The collagen mimetic peptide conjugate of claim 1 , wherein the component of the extracellular matrix is selected from the group consisting of collagen, elastin, fibrillin, fibronectin, laminin; proteoglycans, hyaluronan, chondroitin sulfate, dermatan sulfate, heparin sulfate, heparin, keratan sulfate, and aggrecan.

8. The collagen mimetic peptide conjugate of claim 1 , wherein the polymer is selected from the group consisting of collagen, poly(ethylene oxide) diacrylate (PEODA), poly(ethylene glycol), poly(2-hydroxyethyl methacrylate), polyacrylic alcohol, and polyvinyl alcohol.

9. The collagen mimetic peptide conjugate of claim 1 , wherein the PEG is selected from the group consisting of a star shaped PEG, a multi-armed PEG, a graft linear PEG.

10. The collagen mimetic peptide conjugate of claim 1 , wherein the small molecule is selected from the group consisting of anti-thrombotics, anti-atherosclerosis agents, and cartilage repair agents.

11. The collagen mimetic peptide conjugate of claim 10 , wherein the anti-thrombotic is selected from the group consisting of heparin-CMP, Hirudin-CMP, Saratin-CMP, TenectaplaseCMP, Lanoteplase-CMP, Monteplase-CMP, Pamiteplase-CMP, Abciximab-CMP, Tirofiban-CMP, Epitfibatide-CMP, and Tifacogin-CMP.

12. The collagen mimetic peptide conjugate of claim 10 , wherein the antiatherosclerosis agent is selected from the group consisting of heparin-CMP, Hirudin- CMP, SaratinCMP, Tenectaplase-CMP, Lanoteplase-CMP, Monteplase-CMP, Pamiteplase-CMP, AbciximabCMP, Tirofiban-CMP, Epitfibatide-CMP, and Tifacogin-CMP.

13. The collagen mimetic peptide conjugate of claim 10 , wherein the cartilage repair agent is chondroitin sulfate.

Continuity (4)
Division 11791425
Provisional Application 60630271 · Nov 23, 2004
Provisional Application 60722079 · Sep 29, 2005
Related Publication 20130116405A1 · May 9, 2013