Protein-binding peptide isolated from placenta growth factor
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-039/00
A61K-039/385
A61K-038/18
C07K-014/475
A61K-038/24
C07K-014/51
C07K-014/495
C07K-014/52
A61K-038/00
출원번호
US-0933444
(2013-07-02)
등록번호
US-9879062
(2018-01-30)
발명자
/ 주소
Hubbell, Jeffrey A.
Martino, Mikael
Maithili Briquez, Priscilla S.
출원인 / 주소
Ecole Polytechnique Federale De Lausanne
대리인 / 주소
Christensen, Fonder, Dardi & Herbert PLLC
인용정보
피인용 횟수 :
0인용 특허 :
12
초록
Embodiments of the invention are described, including materials and methods for making molecules and materials that have a specific binding domain of a PlGF2. Embodiments include, for instance, medicaments, biomaterials, biomolecules, molecular fusions, and vaccines.
대표청구항▼
1. A biologic delivery vehicle comprising a molecular fusion of a cytokine that comprises a first endogenous heparin binding domain (HBD) and a peptide,wherein the cytokine is selected from the group consisting of a Vascular Endothelial Growth Factor (VEGF) that comprises an endogenous HBD that prov
1. A biologic delivery vehicle comprising a molecular fusion of a cytokine that comprises a first endogenous heparin binding domain (HBD) and a peptide,wherein the cytokine is selected from the group consisting of a Vascular Endothelial Growth Factor (VEGF) that comprises an endogenous HBD that provides said first HBD, an Epidermal Growth Factor (EGF) that comprises an endogenous HBD that provides said first HBD, a Platelet-Derived Growth Factor (PDGF) that comprises an endogenous HBD that provides said first HBD, a Fibroblast Growth Factor (FGF) that comprises an endogenous HBD that provides said first HBD, a Transforming Growth Factor-Beta (TGF-β) that comprises an endogenous HBD that provides said first HBD, and a Bone Morphogenetic Protein (BMP) that comprises an endogenous HBD that provides said first HBD,wherein the peptide consists of a second heparin binding domain having a sequence chosen from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO:5, SEQ ID NO: 60, and SEQ ID NO: 62, said peptide exhibiting specific binding to fibrinogen,with the biomolecule being free of wild-type full-length PlGF2. 2. The vehicle of claim 1 wherein the molecular fusion comprises a recombinant protein comprising the cytokine and the peptide;a linker covalently bonded with the cytokine and the peptide; ora particle that is joined to the cytokine and to the peptide. 3. The vehicle of claim 2 being soluble or a colloid in a physiological solution with all components of the vehicle being less than about 500 μm in maximum dimension. 4. The vehicle of claim 1 wherein the cytokine that has an endogenous HBD that provides said first HBD comprises VEGF-A, PDGF-AB, PDGF-BB, FGF-2, FGF-18, BMP-2, BMP-7, TGF-β1, or TGF-β2. 5. A biomolecule comprising a cytokine that comprises a first endogenous heparin binding domain (HBD) and a PlGF2 domain that comprises a second heparin binding domain, wherein the cytokine is selected from the group consisting of a Vascular Endothelial Growth Factor (VEGF) that comprises an endogenous HBD that provides said first HBD, an Epidermal Growth Factor (EGF) that comprises an endogenous HBD that provides said first HBD, a Platelet-Derived Growth Factor (PDGF) that comprises an endogenous HBD that provides said first HBD, a Fibroblast Growth Factor (FGF) that comprises an endogenous HBD that provides said first HBD, a Transforming Growth Factor-Beta (TGF-β) that comprises an endogenous HBD that provides said first HBD, and a Bone Morphogenetic Protein (BMP) that comprises an endogenous HBD that provides said first HBD,wherein the PlGF2 domain that comprises the second heparin binding domain consists of a sequence chosen from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 60, and SEQ ID NO: 62,with the biomolecule being free of wild-type full-length PlGF2. 6. The biomolecule of claim 5 wherein the endogenous HBD of the cytokine has been removed or disabled. 7. The biomolecule of claim 5 wherein the cytokine is selected from the group consisting of VEGF-A, PDGF-AB, PDGF-BB, FGF-2, FGF-18, BMP-2, BMP-7, TGF-β1, and TGF-β2. 8. The biomolecule of claim 5 further comprising another biological agent. 9. A fusion protein comprising the biomolecule of claim 5. 10. A biomaterial comprising a matrix, with the matrix comprising a peptide chosen from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 SEQ ID NO: 5, SEQ ID NO: 60, and SEQ ID NO: 62,said peptide exhibiting specific binding to the matrix,wherein the biomaterial is free of wild-type full-length PlGF2. 11. The biomaterial of claim 10 wherein the peptide is specifically bound to the matrix and is available for binding to biomolecules. 12. The biomaterial of claim 10 comprising a plurality of molecular fusions that each comprise one or more of the peptides, with each of the plurality of the molecular fusions having a distinct biologic agent. 13. A method of promoting wound healing in a patient need thereof, said method comprising administering a medicament comprising the biomolecule of claim 5 to the patient. 14. The method of claim 13 wherein the biomolecule provides for an extended release of the peptide. 15. The method of claim 13, with a site of administration of the medicament being chosen from the group consisting of a wound and skin. 16. A method of treating a bone defect in a patient in need thereof, said method comprising administering a medicament comprising the biologic delivery vehicle of claim 1 to the patient. 17. The vehicle of claim 1 with the second heparin binding domain consisting of SEQ ID NO: 4. 18. A method of treating a bone defect in a patient in need thereof, said method comprising administering a medicament comprising the biologic delivery vehicle of claim 17 to the patient. 19. A method of promoting wound healing in a patient in need thereof, said method comprising administering a medicament comprising the biomaterial of claim 10 to the patient. 20. The vehicle of claim 1 wherein the cytokine is VEGF-A165, PDGF-BB, BMP-2, TGF-β1, or TGF-β2. 21. The vehicle of claim 1 wherein the cytokine comprises VEGF-A. 22. The vehicle of claim 1 wherein the cytokine comprises VEGF. 23. The vehicle of claim 1 wherein the cytokine comprises BMP-2 or PDGF-BB. 24. The biomolecule of claim 5 wherein the cytokine is VEGF-A165, PDGF-BB, BMP-2, TGF-β1, or TGF-β2. 25. The biomolecule of claim 5 wherein the cytokine comprises VEGF-A. 26. The biomolecule of claim 5 wherein the cytokine comprises BMP-2 or PDGF-BB. 27. The method of claim 16, with a site of administration of the medicament being bone. 28. The method of claim 19, with a site of administration of the medicament being chosen from the group consisting of a wound skin.
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