IP Library Granted Patent US 7,981,862
Granted Patent B2
US 7,981,862 · App. 11/767,391 · Granted Jul 19, 2011

Composition comprising BMP-2 amplifier/co-activator for enhancement of osteogenesis

Assignee: BioSurface Engineering Technologies, Inc.
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Quick Facts
Patent No.
US 7,981,862
App. No.
11/767,391
Granted
Jul 19, 2011
Kind
B2
Abstract

A composition comprising a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor and an osteoconductive material where the synthetic growth factor analogue is attached to and can be released from the osteoconductive material and is an amplifier/co-activator of osteoinduction.

Claims (32)

1. A composition of formula II:

wherein:

X is a peptide chain that (i) has a minimum of three amino acid residues, (ii) has a maximum of about fifty amino acid residues, and (iii) binds specifically to a cell surface receptor, wherein X is selected from the group consisting of SEQ ID NOs: 7-19;

R 1 is independently hydrogen, such that the terminal group is NH 2 ;

R 4 is OH such that the terminal group is a carboxyl;

R 5 is lysine;

R 6 is lysine;

Y is Hx-Hx-Hx covalently bonded to R 5 and Z; and

Z is a non-signaling peptide chain that includes a heparin binding domain comprising an amino acid sequence that comprises (i) a minimum of one heparin binding motif, (ii) a maximum of about ten heparin binding motifs, and (iii) a maximum of about thirty amino acids, wherein Z is selected from the group consisting of SEQ ID NOs: 1-6.

2. The composition of claim 1 wherein the structure of the composition is AISMLYLDENEKVVLKK(AISMLYLDENEKVVLK)HxHxHxRKRLDRIAR wherein X is AISMLYLDENEKVVL (SEQ ID NO:7); and Z is RKRLDRIAR (SEQ ID NO: 5).

3. A composition comprising:

a synthetic growth factor analogue having the structure shown in formula II:

wherein:

X is SEQ ID NO: 7;

Y is Hx-Hx-Hx;

Z is SEQ ID NO: 5;

R 1 is independently hydrogen such that the N-terminal group is NH 2 ;

R 4 is OH such that the terminal group is a carboxyl;

R 5 is Lysine; and

R 6 is lysine; and

an osteoconductive material comprising one or more of an inorganic material, a synthetic polymer, a natural polymer, an allograft bone, or combination thereof,

wherein the synthetic growth factor analogue is attached to and can be released from the osteoconductive material and is an amplifier/co-activator of osteoinduction.

4. The composition of claim 3 wherein the growth factor analogue modulates the response to bone morphogenetic proteins.

5. The composition of claim 3 wherein the growth factor analogue modulates the ostetoinductive environment by amplifying or co-activating cell growth, chemotaxis, or cell attachment.

6. The composition of claim 3 wherein the osteoconductive material is selected from hydroxyapaptite, tricalcium phosphate, collagen, hyaluronate, calcium sulfate, polyglycolic acid fibers, polylactic-co-glycolic acid, allograft or any combination thereof.

7. The composition of claim 3 , comprising a calcium sulfate salt as the osteoconductive material.

8. The composition of claim 7 wherein the calcium sulfate salt is between about 30-80 wt %.

9. The composition of claim 3 wherein the osteoconductive material contains hydroxyapatite or tricalcium phosphate, or both.

10. The composition of claim 3 wherein the osteoconductive material contains about 20 wt % hydroxyapatite and about 80 wt % tricalcium phosphate.

11. The composition of claim 3 wherein the osteoconductive material is formed into a granule, a putty, a powder, a gel, a block or a combination thereof.

12. The composition of claim 11 wherein the granule further comprises silicate substituting a portion of the phosphate ions in the hydroxyapatite lattice.

13. The composition of claim 3 which contains excipients which do not interfere with the growth factor analogue binding to the osteoconductive matrix.

Assignments (5)
CONFIRMATORY LICENSE Recorded Jun 5, 2026
From: BROOKHAVEN SCIENCE ASSOCIATES, LLC
To: U.S. DEPARTMENT OF ENERGY
Reel/Frame 074861/0349 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 26, 2017
From: PEÑA, LOUIS A; LIN, XINHUA
To: BROOKHAVEN SCIENCE ASSOCIATES, LLC
Reel/Frame 042817/0098 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 10, 2015
From: FERRING INTERNATIONAL CENTER S.A.
To: FERRING B.V.
Reel/Frame 036062/0499 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2015
From: BIOSURFACE ENGINEERING TECHNOLOGIES, INC.
To: FERRING INTERNATIONAL CENTER S.A.
Reel/Frame 035769/0122 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2007
From: ZAMORA, PAUL O.; ATKINSON, BRENT LEE
To: BIOSURFACE ENGINEERING TECHNOLOGIES, INC.
Reel/Frame 019830/0215 →
Continuity (7)
Continuation In Part 11064039 · Feb 22, 2005
Continuation In Part 10644703 · Aug 19, 2003
Continuation In Part 10224268 · Aug 20, 2002
Continuation In Part 11064039
Provisional Application 60805594 · Jun 22, 2006
Provisional Application 60547012 · Feb 20, 2004
Related Publication 20080063622A1 · Mar 13, 2008