WO2007150053B1 - Composition and method for delivery of bmp-2 amplifier/co-activator for enhancement of osteogenesis - Google Patents

Composition and method for delivery of bmp-2 amplifier/co-activator for enhancement of osteogenesis

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Publication number
WO2007150053B1
WO2007150053B1 PCT/US2007/071946 US2007071946W WO2007150053B1 WO 2007150053 B1 WO2007150053 B1 WO 2007150053B1 US 2007071946 W US2007071946 W US 2007071946W WO 2007150053 B1 WO2007150053 B1 WO 2007150053B1
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WO
WIPO (PCT)
Prior art keywords
composition
growth factor
osteoconductive material
osteoconductive
bone
Prior art date
Application number
PCT/US2007/071946
Other languages
French (fr)
Other versions
WO2007150053A3 (en
WO2007150053A2 (en
Inventor
Paul Zamora
Brent Lee Atkinson
Original Assignee
Biosurface Eng Tech Inc
Paul Zamora
Brent Lee Atkinson
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biosurface Eng Tech Inc, Paul Zamora, Brent Lee Atkinson filed Critical Biosurface Eng Tech Inc
Priority to CA2692240A priority Critical patent/CA2692240C/en
Priority to EP07798963A priority patent/EP2046350A4/en
Priority to JP2009516753A priority patent/JP2009541358A/en
Publication of WO2007150053A2 publication Critical patent/WO2007150053A2/en
Publication of WO2007150053A3 publication Critical patent/WO2007150053A3/en
Publication of WO2007150053B1 publication Critical patent/WO2007150053B1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Toxicology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Immunology (AREA)
  • Vascular Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Rheumatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Materials For Medical Uses (AREA)
  • Polymers & Plastics (AREA)

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

AMENDED CLAIMS received by the International Bureau on 06 February 2008
WHAT IS CLAIMED IS; 1. A compound of formula II:
Figure imgf000002_0001
wherein: the compound of formula II modulates the response to bone morphogenetic proteins;
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;
Ri is independently hydrogen, such that the terminal group is NH2, an acyl group with a linear or branched C1 to C17 alkyl, aryl, heteroaryl, alkene, alkenyl or aralkyl chain including an N-terminus NHa, NH3 +, or NH group or a corresponding acylated derivative, or is amino acid, a dipeptide or a tripeptide with an N-terminus NH2, NH3 +, or NH group;
Ru is independently a linker comprising a chain from 0 to about 15 backbone atoms covalently bonded to R3 when the linker is greater than 0 atoms;
Rs is a trifunctional alpha amino acid residue, wherein X is covalently bonded through a side chain of R3;
R4 is OH such that the terminal group is a carboxyl, NH2, an acyl group with a linear or branched Ci to Cn alkyl, aryl, heteroaryl, alkene, alkenyl or aralkyl chain including an N-terminus NH2, NH3 +, or NH group or a corresponding acylated derivative., or NH-R i ;
Y is a linker comprising a chain from 0 to about 50 backbone atoms covalently bonded to Rs 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 aboul ten heparin binding motifs, and (iii) a maximum of aboul thirty amino acids.
2. A composition comprising: a synthetic growth factor analogue of claim 3 ; and an osteoinductive 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 amplifter/co-activator of osteoinduction.
3. The compound of claim 2 wherein the osteoconductive material is formed into a granule, a putty, a powder, a gel, a block or a combination thereof.
4. The composition of claim 2 wherein the growth factor analogue is AISMLYLDENEKWLKK(AISMLYLDENEKWLK)HxHxHxREaILDRIARNH2
6. The composition of claim 2 wherein the growth factor analogue modulates the osteoconductive environment by amplifying or co-activating cell growth, chemotaxis, or cell attachment.
7. The composition of claim 2, further comprising a calcium sulfate salt as the osteoconductive material.
8. The composition of claim 7 wherein the calcium sulfate is between about 30-80 wt %.
9. The composition of claim 2 wherein the osteoconductive material contains about 0-300 wt % hydroxyapatite and about 0-100 wt % tricalcium phosphate.
10. The composition of claim 2 wherein the osteoconductive material contains about 20 wt % hydroxyapatite and about 80 wt % tricalcium phosphate.
11. The composition of claim 2 wherein the osteoconductive material is selected from hydroxyapaptitc, tricalcium phosphate, collagen, hyaluronate, calcium sulfate, polygiycolic actd fibers, polylactic-co-glycolic acid, allograft or any combination thereof.
12. The composition of claim 2 in which the formulation contains excipients which do not interfere with peptide binding to the osteoconductive matrix.
13. The composition of claim 2 wherein the granule further comprises silicate substituting a portion of the phosphate ions in the hydroxyapatite lattice.
14. A method for treating bone lesions comprising: coating an osteoinductive material of claim 2 with the synthetic growth factor analogue of claim 1 to generate an osteoconductive material with the growth factor analogue releasably attached thereto; and implanting the coated osteoconductive material in a bone lesion.
15. The method of claim 14 in which an exogenous or recombinant bone growth factor is added.
16. The method of claim 14 wherein the osteoconductive material comprises one or more inorganic material, collagen, hyaluronate, Polylaclic acid, Polyglycolic acid. allograft or any combination thereof.
17. The method of claim 14 wherein the osteoconductive material are formed from granules, polymers, powders, gel, cement, putty or any combination thereof.
IS. The method of claim 14 wherein the osteoconductive material is used in combination with a load bearing device to treat bone lesions.
19. The method of claim 18 wherein the load bearing device Is selected from cages, wedges, rods, pedicle screws, vertebral body replacement, intervertebral body fusion device or rings for bone fusion.
20. The method of claim 18 wherein the treatment of the bone lesion results in spine fusion.
21. The method of claim 14 wherein ihe method further comprises adding host bone chips or bone marrow aspirate with the graft material,
22. The method of claim 14 wherein the synthetic growth factor analogue comprises AISMLYLDENEKVVLKIC(AISMLYLDENEKVVLK)HXHXMXRKRLDRIARNH2.
23. The method of claim 14 wherein releasing the synthetic growth factor analogue is rate-controlled by manipulating the composition of the osteoconductive material, concentration of synthetic growth factor analogue attached to the osteoconductive material or the physical properties of the osteoconductive material.
24. A kit comprising: a lyophilized vial of synthetic growth factor analogue (with or without excipients); and a container of osteoconductive material.
PCT/US2007/071946 2006-06-22 2007-06-22 Composition and method for delivery of bmp-2 amplifier/co-activator for enhancement of osteogenesis WO2007150053A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CA2692240A CA2692240C (en) 2006-06-22 2007-06-22 Composition and method for delivery of bmp-2 amplifier/co-activator for enhancement of osteogenesis
EP07798963A EP2046350A4 (en) 2006-06-22 2007-06-22 Composition and method for delivery of bmp-2 amplifier/co-activator for enhancement of osteogenesis
JP2009516753A JP2009541358A (en) 2006-06-22 2007-06-22 Compositions and methods for delivering a BMP-2 amplification factor / co-activator to enhance bone formation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US80559406P 2006-06-22 2006-06-22
US60/805,594 2006-06-22

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WO2007150053A3 WO2007150053A3 (en) 2008-04-10
WO2007150053B1 true WO2007150053B1 (en) 2008-05-15

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EP (1) EP2046350A4 (en)
JP (1) JP2009541358A (en)
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