Granted Patent
B2
US 12,264,187 · App. 18/046,810 · Granted Apr 1, 2025
Compositions and methods for targeted therapeutic delivery to bone
Inventors:
Luis Alvarez (Lexington, MA); David Stewart (Monrovia, MD); Hyeon Park (Clarksburg, MD); Todd Heil (Mt. Airy, MD)
Assignee:
Theradaptive, Inc.
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Abstract
Provided herein are polypeptides comprising a therapeutic targeted for delivery to an organ or tissue, and uses thereof.
Claims (19)
1. A polypeptide composition comprising: a targeting polypeptide comprising a sequence at least 95% identical to SEQ ID NO: 22 (LLADTTHHRPWT VIGESTHHRPWS IIGESSHHKPFT GLGDTTHHRPWG ILAESTHHKPWT), connected to a therapeutic polypeptide comprising a sequence at least 95% identical to a sequence selected from the group consisting of SEQ ID NOs: 32, 55, 58, 59, 60, 61, 62, 64, 65 and 71, wherein the targeting polypeptide binds to calcium phosphate.
2. The polypeptide composition of claim 1 , wherein the targeting polypeptide comprises the sequence of SEQ ID NO: 22.
3. The polypeptide composition of claim 1 , wherein therapeutic polypeptide comprises the sequence of SEQ ID NO: 32, 55, 58, 59, 60, 61, 62, 64, 65 or 71.
4. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 32.
5. The polypeptide composition of claim 4 , wherein the therapeutic polypeptide comprises the sequence of SEQ ID NO: 32.
6. The polypeptide composition of claim 4 , wherein the targeting polypeptide connected to the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 502 or SEQ ID NO: 503.
7. The polypeptide composition of claim 6 , wherein the targeting polypeptide connected to the therapeutic polypeptide comprises the sequence of SEQ ID NO: 502 or SEQ ID NO: 503.
8. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 55.
9. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 58.
10. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 59.
11. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 60.
12. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 61.
13. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 62.
14. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 64.
15. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 65.
16. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 71.
17. The polypeptide composition of claim 1 , wherein the therapeutic polypeptide has osteogenic activity.
18. A polypeptide composition comprising: a targeting polypeptide comprising a sequence at least 95% identical to SEQ ID NO: 22 (LLADTTHHRPWT VIGESTHHRPWS IIGESSHHKPFT GLGDTTHHRPWG ILAESTHHKPWT), connected to a therapeutic polypeptide comprising a sequence at least 95% identical to SEQ ID NO: 46, 47, 48, 49, 50, 53, 54 or 75, wherein the targeting polypeptide binds to calcium phosphate.
19. A polypeptide composition comprising: a targeting polypeptide comprising a sequence at least 95 % identical to SEQ ID NO: 22 (LLADTTHHRPWT VIGESTHHRPWS IIGESSHHKPFT GLGDTTHHRPWG ILAESTHHKPWT), connected to a therapeutic polypeptide comprising a sequence at least 95 % identical to a sequence selected from the group consisting of SEQ ID NOs: 82- 100, wherein the targeting polypeptide binds to calcium phosphate.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 28, 2023
From: ALVAREZ, LUIS; STEWART, DAVID; PARK, HYEON; HEIL, TODD
To: THERADAPTIVE, INC.
Reel/Frame 063482/0718 →
CONFIRMATORY LICENSE
Recorded Mar 7, 2023
From: THERADAPTIVE, INC.
To: UNITED STATES GOVERNMENT
Reel/Frame 062967/0563 →
Continuity (3)
Continuation
PCTUS2021027230
· Apr 14, 2021
Provisional Application
63010639
· Apr 15, 2020
References Cited (219)
US 5122458A
· Post et al.
· 1992
[cited by applicant]
US 5152791A
· Hakamatsuka et al.
· 1992
[cited by applicant]
US 5219740A
· Miller et al.
· 1993
[cited by applicant]
US 5491082A
· Suzuki et al.
· 1996
[cited by applicant]
US 5820632A
· Constantz et al.
· 1998
[cited by applicant]
US 5906828A
· Cima et al.
· 1999
[cited by applicant]
US 6207453B1
· Maass et al.
· 2001
[cited by applicant]
US 6455495B1
· Orgel et al.
· 2002
[cited by applicant]
US 6949251B2
· Dalal et al.
· 2005
[cited by applicant]
US 7172629B2
· McKay
· 2007
[cited by applicant]
US 7323542B2
· Balian
· 2008
[cited by applicant]
US 7572766B2
· Beyer, Jr. et al.
· 2009
[cited by applicant]
US 7871978B2
· Balian
· 2011
[cited by applicant]
US 7977313B2
· Gron et al.
· 2011
[cited by applicant]
US 8022040B2
· Bertozzi et al.
· 2011
[cited by applicant]
US 8075562B2
· Murphy et al.
· 2011
[cited by applicant]
US 8137664B2
· Nycz et al.
· 2012
[cited by applicant]
US 8383769B2
· Peled et al.
· 2013
[cited by applicant]
US 8420774B2
· Murphy et al.
· 2013
[cited by applicant]
US 8778869B2
· Murphy et al.
· 2014
[cited by applicant]
US 8846860B2
· Murphy et al.
· 2014
[cited by applicant]
US 9295755B2
· Murphy
· 2016
[cited by applicant]
US 9809635B2
· Qin et al.
· 2017
[cited by applicant]
US 20040197892A1
· Moore et al.
· 2004
[cited by applicant]
US 20050084962A1
· Simon
· 2005
[cited by applicant]
US 20060040354A1
· O'Keefe
· 2006
[cited by applicant]
US 20060193916A1
· Lazarova et al.
· 2006
[cited by applicant]
US 20100049322A1
· McKay
· 2010
[cited by applicant]
US 20100080850A1
· Hubbell et al.
· 2010
[cited by applicant]
US 20100260673A1
· Cao et al.
· 2010
[cited by applicant]
US 20190322702A1
· Alvarez et al.
· 2019
[cited by applicant]
US 20200031896A1
· Cao
· 2020
[cited by applicant]
US 20200102458A1
· Alemseghed et al.
· 2020
[cited by applicant]
US 20210023269A1
· Taira et al.
· 2021
[cited by applicant]
US 20210214408A1
· Low et al.
· 2021
[cited by applicant]
US 20220323641A1
· Alvarez et al.
· 2022
[cited by applicant]
US 20220395610A1
· Taira et al.
· 2022
[cited by applicant]
US 20230203115A1
· Alvarez et al.
· 2023
[cited by applicant]
US 20230233740A1
· Alvarez et al.
· 2023
[cited by applicant]
US 20240018187A1
· Alvarez
· 2024
[cited by applicant]
US 20240131228A1
· Alvarez et al.
· 2024
[cited by applicant]
CN 102532272A
· 2012
[cited by applicant]
CN 104193803A
· 2014
[cited by applicant]
JP 2014508555A
· 2014
[cited by applicant]
WO WO0202593A2
· 2002
[cited by applicant]
WO WO03026590A2
· 2003
[cited by applicant]
WO WO2005039616A1
· 2005
[cited by applicant]
WO WO2006012414A2
· 2006
[cited by applicant]
WO WO2006078464A2
· 2006
[cited by applicant]
WO WO2009020550A2
· 2009
[cited by applicant]
WO WO2009108934A2
· 2009
[cited by applicant]
WO WO2009126648A1
· 2009
[cited by applicant]
WO WO2010051032A1
· 2010
[cited by applicant]
WO WO2010052715A2
· 2010
[cited by applicant]
WO WO2012078671A2
· 2012
[cited by applicant]
WO WO2017096328A1
· 2017
[cited by applicant]
WO WO2020077265A1
· 2020
[cited by applicant]
WO WO2020139901A1
· 2020
[cited by applicant]
WO WO2020163766A1
· 2020
[cited by applicant]
WO WO2021194604A2
· 2021
[cited by applicant]
WO WO2021211683A2
· 2021
[cited by applicant]
Bang et al., Scientific Reports, 2020, vol. 10: 10576.
[cited by examiner]
Karoulias et al., Bone Reports, 2021, vol. 14: 101092.
[cited by examiner]
Osta et al., Front. Immunol., 2014, vol. 5, Article 48.
[cited by examiner]
Peng et al., Comp. Biochem. Physiol., Part A, 2009, vol. 153(1):83-87.
[cited by examiner]
Qu et al., J. Biol. Chem., 2019, vol. 294(52):19877-19888.
[cited by examiner]
Alonso-Camino et al.: CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors. Mol. Ther. Nucleic Acids. 2(5):e93 (2013).
[cited by applicant]
Batt et al.: Characterization of the Polyomavirus Late Polyadenylation Signal. Mol. Cell Biol. 15(9):4783-4790 (1995).
[cited by applicant]
Boris-Lawrie et al.: Recent advances in retrovirus vector technology. Cur. Opin. Genet. Development. 3:102-109 (1993).
[cited by applicant]
Burns et al., “Vesicular Stomatitis Virus G Glycoprotein Pseudotyped Retroviral Vectors: Concentration to Very High Titer and Efficient Gene Transfer into Mammalian and Nonmammalian Cells,” Proc. Natl. Acad. Sci. USA 90…
[cited by applicant]
Carlens et al.: Ex vivo T lymphoccyte expansion for retroviral transduction: Influence of serum-free media on variations in cell expansion rates and lymphocyte subset distribution. Exp. Hematol. 28(10):1137-1146 (2000).
[cited by applicant]
Cavalieri, et al., Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence. Blood 102(2):497-505 (2003).
[cited by applicant]
Chhabra et al.: BMP-14 Deficiency Inhibits Long Bone Fracture Healing. A Biochemical, Histologic, and Radiographic Assessment. J Orthop Trauma 19(9):629-634 (2005).
[cited by applicant]
Cooper, et al. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood. Feb. 15, 2003;101(4):1637-44. Epub Oct. 10, 2002.
[cited by applicant]
Drosse et al.: Tissue Engineering Part C 14(1):79-88 (2008).
[cited by applicant]
Histing et al.: Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting. Bone. 49:591-599 (2011).
[cited by applicant]
Kim et al.: In vitro and in vivo osteogenic activity of licochalcone A. Amino Acids. 42:1455-1465 (2012).
[cited by applicant]
Lee et al.: In Vitro and In Vivo Osteogenic Activity of Largazole. ACS Med. Chem. Lett. 2(3):248-251 (2011).
[cited by applicant]
Levitt et al.: Definition of an efficient synthetic poly(A) site. Genes Dev. 3(7):1019-1025 (1989).
[cited by applicant]
Makley et al.: The Effect of Reduced Barometric Pressure on Fracture Healing in Rats. J Bone Joint Surg Am 49(5):903-914 (1967).
[cited by applicant]
Marino et al.: Fracture Healing in Rats Exposed to Extremely Low-Frequency Electric Fields. Clin Orthop Relat Res. (145):239-244 (1979).
[cited by applicant]
Miller, A.D. “Retrovirus packaging cells.” Human Gene Therapy 1990; 1(1): 5-14.
[cited by applicant]
Miller et al., “Improved retroviral vectors for gene transfer and expression.” Biotechniques Oct. 1989; 7(9):980-982; 984-986; 989-990.
[cited by applicant]
Orkin et al.: Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. EMBO J. 4(2):453-456 (1985).
[cited by applicant]
Park et al., “Treating cancer with genetically engineered T cells,” Trends Biotechnol., 29(11):550-557, 2011.
[cited by applicant]
PCT/US2021/027230 International Invitation to Pay Additional Fees dated Jul. 20, 2021.
[cited by applicant]
PCT/US2021/027230 International Search Report and Written Opinion dated Oct. 4, 2021.
[cited by applicant]
Poser et al.: A Standardized Critical Size Defect Model in Normal and Osteoporotic Rats to Evaluate Bone Tissue Engineered Constructs. Hindawi Publishing Corporation. BioMed Research International; Article ID 348635 (20…
[cited by applicant]
Scarpa et al.: Characterization of recombinant helper retroviruses from moloney-based vectors in ecotropic and amphotropic packaging cell lines. Virology. 180(2):849-852 (1991).
[cited by applicant]
Schek et al.: Definition of the Upstream Efficiency Element of the Simian virus 40 Late Polyadenylation Signal by Using In Vitro Analyses. Mol. Cell Biol. 12(12):5386-5393 (1992).
[cited by applicant]
Szymanski et al.: Development and Validation of a Robust and Versatile One-plasmid Regulated Gene Expression System. Mol. Therapy. 15(7):1340-1347 (2007).
[cited by applicant]
Verhoeyen et al., “Lentiviral Vector Gene Transfer into Human T Cells,” Methods in Molecular Biology, Methods and Protocols 506:97-114, 2009.
[cited by applicant]
Wang et al.: In vivo osteogenic activity of bone marrow stromal stem cells transfected with Ad-GFP-hBMP-2. Genetics Mol. Res. 13(2):4456-4465 (2014).
[cited by applicant]
Wang et al.: Phenotypic and Functional Attributes of Lentivirus-modified CD19-specific Human CD8+ Central Memory T Cells Manufactured at Clinical Scale. J. Immunother. 35(9):689-701 (2012).
[cited by applicant]
Woychik et al.: Requirement for the 3′ flanking region of the bovine growth hormone gene for accurate polyadenylylation. Proc. Natl. Acad. Sci. U.S.A. 81(13):3944-3948 (1984).
[cited by applicant]
Alvarez et al., Tethering of epidermal growth factor (EGF) to beta tricalcium phosphate (βTCP) via fusion to a high affinity, multimeric βTCP-binding peptide: effects on human multipotent stromal cells/connective tissue…
[cited by applicant]
Bateman et al., Platelet-derived growth factor enhancement of two alloplastic bone matrices. J. Periodontology 76(11):1833-1841 (2005).
[cited by applicant]
Bradshaw et al., SPaRC-null mice exhibit increased adiposity without significant differences in overall body weight. PNaS 100(10):6045-6050 (2003).
[cited by applicant]
Bublil et al., The EGF receptor family: spearheading a merger of signaling and therapeutics. Current Opinion in Cell Biology 19:124-134 (2007).
[cited by applicant]
Cao et al.: Phage display peptide probes for imaging early response to bevacizumab treatment. Amino Acids. 41(5):1103-1112 (2011).
[cited by applicant]
Carrodeguas et al., Alpha-tricalcium phosphate: synthesis, properties and biomedical applications. Acta Biomaterialia 7:3536-3546 (2011).
[cited by applicant]
Chan et al., Expression of epidermal growth factor in transgenic mice causes growth retardation. Journal of Biological Chemistry 275(49):38693-38698 (2000).
[cited by applicant]
Cheng et al., A new protocol for high-yield purification of recombinant human CXCL8(3-72)K11R/G31P expressed in
[cited by applicant]
Cho et al., The effects of synthetic peptide derived from hBMP-2 on bone formation in rabbit calvarial defect. Tissue Engineering and Regenerative Medicine 5(3):488-497 (2008).
[cited by applicant]
Citri et al., EGF-ERBB signalling: towards the systems level. Molecular Cell Biology 7:505-516 (2006).
[cited by applicant]
Dickens et al., Crystallographic studies of the role of Mg as a stabilizing impurity in beta-Ca3(PO4)2. I. The crystal structure of pure beta-Ca3(PO4)2. Journal of Solid State Chemistry 10(3):232-248 (1974).
[cited by applicant]
Dickerson et al., Identification and design of peptides for the rapid, high-yield formation of nanoparticulate TiO2 from aqueous solutions at room temperature. Chemistry of Materials 20(4):1578-1584 (2008).
[cited by applicant]
Dudak et al., Enhancing the affinity of SEB-binding peptides by repeating their sequence. Biopolymers 98(2):145-154 (2011).
[cited by applicant]
Erbe et al., Potential of an ultraporous beta-tricalcium phosphate synthetic cancellous bone void filler and bone marrow aspirate composite graft. Eur. Spine J. 10:S141-S146 (2001).
[cited by applicant]
Fan et al., Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells. Stem Cells 25:1241-1251 (2007).
[cited by applicant]
Fleming Jr. et al.: Intraoperative harvest and concentration of human bone marrow osteoprogenitors for enhancement of spinal fusion. In Orthopedic Tissue Engineering Basic Science and Practice, V.M. Goldberg and A.I. Ca…
[cited by applicant]
Freeman M., Reiterative use of the EGF receptor triggers differentiation of all cell types in the
[cited by applicant]
Friedlaender et al., Osteogenic protein-1 (bone morphogenctic protein-7) in the treatment of tibial nonunions. J. Bone Joint Surg. Am., 83(A Suppl 1, Pt 2):S151-S158 (2001).
[cited by applicant]
Gao et al., Molecular cloning, structure, expression, and chomosomal localization of the human osterix (SP7) gene. Gene 2341:101-110 (2004).
[cited by applicant]
Gibbs et al., Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation. Wound Repair and Regeneration 8(3):192-203 (2000).
[cited by applicant]
Glick et al., Ligand recognition by influenza virus. The Journal of Biological Chemistry 266(35):23660-23669 (1991).
[cited by applicant]
Griffith L.G., Emerging design principles in biomaterials and scaffolds for tissue engineering. Ann. N.Y. Acad. Sci. 961:83-95 (2002).
[cited by applicant]
Gronthos et al., The growth factor requirements of STRO-1-positive human bone marrow stromal precursosrs under serum-deprived conditions in vitro. Blood 85(4):929-940 (1995).
[cited by applicant]
Gungormus et al., Regulation of in vitro calcium phosphate mineralization by combinatorially selected hydroxyapatite-binding peptides. Biomacromolecules 9(3):966-973 (2008).
[cited by applicant]
Hamilton et al., Improved bone morphogenetic protein-2 retention in an injectable collagen matrix Using Bifunctional Peptides. PLoS One 8(8):e70715 [1-10] (2013).
[cited by applicant]
Handl et al., Hitting multiple targets with multimeric ligands. Expert Opin. 8(6):565-586 (2004).
[cited by applicant]
Hoang et al., Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature 425:977-980 (2003).
[cited by applicant]
Huang et al., MimoDB 2.0: a mimotope database and beyond. Nucleic Acids Research 40(Database issue):D271-D277 (2012).
[cited by applicant]
Jay et al., Engineered bivalent ligands to bias ErbB receptor-mediated signaling and phenotypes. J. Biol. Chem. 286:27729-27740 (2011).
[cited by applicant]
Kenan et al., Peptide-PEG amphiphiles as brief communication cytophobic coatings for mammalian and bacterial cells. Chemistry & Biology 13:695-700 (2006).
[cited by applicant]
Kim et al., Extracellular calcium-binding peptide-modified ceramics stimulate regeneration of calvarial bone defects. Tissue Engineering and Regenerative Medicine 13:57-65 (2016).
[cited by applicant]
Kimura et al., Effects of platelet derived growth factor, epidermal growth factor and transforming growth factor-beta on the growth of human marrow fibroblasts. British Journal of Haematology 69(1):9-12 (1988).
[cited by applicant]
Kitov et al., Optimization of tether length in nonglycosidically linked bivalent ligands that target sites 2 and 1 of a shiga-like toxin. J. Am. Chem. Soc. 125:3284-3294 (2003).
[cited by applicant]
Kratchmarova et al., Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation. Science 308:1472-1477 (2005).
[cited by applicant]
Krueger et al., Tailoring chimeric ligands for studying and biasing ErbB receptor family interactions. Angew. Chem. Int. Ed. 53:2662-2666 (2014).
[cited by applicant]
Kuhl et al., Tethered epidermal growth factor as a paradigm for growth factor-induced stimulation from the solid phase. Nature Medicine 2(9):1022-1027 (1996).
[cited by applicant]
Kuznetsov et al., Factors required for bone marrow stromal fibroblast colony formation in vitro. British Journal of Haematology 97:561-570 (1997).
[cited by applicant]
Maheshwari et al., Biophysical integration of effects of epidermal growth factor and fibronectin on fibroblast migration. Biophysical Journal 76:2814-2823 (1999).
[cited by applicant]
Marcantonio et al., The influence of tethered epidermal growth factor on connective tissue progenitor colony formation. Biomaterials 30(27):4629-4638 (2009).
[cited by applicant]
Martino et al., Extracellular matrix-inspired growth factor delivery systems for bone regeneration. Advanced Drug Delivery Reviews 94:41-52 (2015).
[cited by applicant]
Martino et al., Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343(6173):885-888 (2014).
[cited by applicant]
Martyre et al., Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-β in patients with myelofibrosis with myeloid metaplasia. British Journal of Haematology. 77:80-86 (1991).
[cited by applicant]
Matsubara et al., BMP2 regulates osterix through Msx2 and Runx2 during osteoblast differentiation. Journal of Biological Chemistry 283:29119-29125 (2008).
[cited by applicant]
Mehta et al., Synergistic effects of tethered growth factors and adhesion ligands on DNA synthesis and function of primary hepatocytes cultured on soft synthetic hydrogels. Biomaterials 31(17):4657-4671 (2010).
[cited by applicant]
Miettinen et al., Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure. Nature Genetics 22:69-73 (1999).
[cited by applicant]
Mikami et al., Inductive effects of dexamethasone on the mineralization and the osteoblastic gene expressions in mature osteoblast-like ROS17/2.8 cells. Biochem Biophys Res Comm 362(2):368-372 (2007).
[cited by applicant]
Moll et al., Designed heterodimerizing leucine zippers with a range of pls and stabilities up to 10exp(-15) M. Protein Science 10:649-655 (2001).
[cited by applicant]
Muschler et al.: Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am 86-A:1541-1558 (2004).
[cited by applicant]
Muschler et al., Engineering principles of clinical cell-based tissue engineering. Journal of Bone Joint Surg. 86-A(7):1541-1558 (2004).
[cited by applicant]
NCBI. GenBank Accession No. NP_001191.1: Bone morphogentic protein 2 preproprotein [
[cited by applicant]
Nuschke et al., Epidermal growth factor tethered to beta-tricalcium phosphate bone scaffolds via a high-affinity binding peptide enhances survival of human mesenchymal stem cells/multipotent stromal cells in an immune-c…
[cited by applicant]
Ogose et al., Comparison of hydroxyapatite and beta tricalcium phosphate as bone substitutes after exclusion of bone tumors. Biomedical Materials Research Part B: Applied Biomaterials 72B:94-101 (2005).
[cited by applicant]
Orii et al., Beta-tricalcium phosphate (beta-TCP) graft combined with bone marrow stromal cells (MSCs) for posterolateral spine fusion. J Med Dent Sci 52:51-57 (2005).
[cited by applicant]
Owen et al., Clonal analysis in vitro of osteogenic differentiation of marrow DFU-F. J Cell Science 87:731-738 (1987).
[cited by applicant]
PCT/US2011/063592 international Preliminary Report on Patentability dated Jun. 20, 2013.
[cited by applicant]
PCT/US2011/063592 international Search Report and Written Opinion dated Feb. 14, 2013.
[cited by applicant]
PCT/US2019/055939 International Preliminary Report on Patentability dated Apr. 22, 2021.
[cited by applicant]
PCT/US2019/055939 International Search Report and Written Opinion dated Feb. 5, 2020.
[cited by applicant]
PCT/US2021/012219 International Invitation to Pay Additional Fees dated Aug. 27, 2021.
[cited by applicant]
PCT/US2021/012219 International Preliminary Report on Patentability dated Sep. 15, 2022.
[cited by applicant]
PCT/US2021/012219 International Search Report and Written Opinion dated Nov. 23, 2021.
[cited by applicant]
PCT/US2021/027230 International Preliminary Report on Patentability dated Oct. 26, 2022.
[cited by applicant]
Pickens et al., Nonspanning bivalent ligands as improved surface receptor binding inhibitors of the cholera toxin B pentamer. Chemistry & Biology 11:1205-1215 (2004).
[cited by applicant]
Pinkas-Kramarski et al., Diversification of neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. The EMBO Journal 15(10):2452-2467 (1996).
[cited by applicant]
Platt et al., Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells. J. Cell Physiol. 221(2):306-317 (2009).
[cited by applicant]
Qin et al., Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation. Journal of Biological Chemistry 280:3974-3981 (2005).
[cited by applicant]
Rieker et al., Molecular applications of fusions to leucine zippers. Methods in Enzymology 328:282-296 (2000).
[cited by applicant]
Roy et al.: Identification of a Highly Specific Hydroxyapatite-binding Peptide using Phage Display. Advanced Materials. VCH Publishers. 20(10):1830-1836 (2008).
[cited by applicant]
Sanghvi et al., Biomaterials functionalization using a novel peptide that selectively binds to a conducting polymer. Nature Materials 4:496-502 (2005).
[cited by applicant]
Satomura et al., Receptor tyrosine kinase expression in human bone marrow stromal cells. Journal of Cellular Physiology 177(3):426-438 (1998).
[cited by applicant]
Segvich, S.J. Design of peptides with targeted apatite and human bone marrow stromal cell adhesion for bone tissue engineering. (Doctoral Dissertation), Proquest UMI Publication No. 3343205 (2009).
[cited by applicant]
Seker et al., Quantitative affinity of genetically engineered repeating polypeptides to inorganic surfaces. Biomacromolecules 10:250-257 (2009).
[cited by applicant]
Shen et al., Tuning the erosion rate of artificial protein hydrogels through control of network topology. Nature Materials 5:153-158 (2006).
[cited by applicant]
Sibilia et al., Mice humanized for the EGF receptor display hypomorphic phenotypes in skin, bone and heart. Development 130(19):4515-4525 (2003).
[cited by applicant]
Stemcell Technologies product description for human bone marrow stromal cells, frozen, Cat No. 70022 (2014; made of record).
[cited by applicant]
Su et al., Conformational Selectivity of Peptides for Single-Walled Carbon Nanotubes. J. Phys. Chem. B 110(47):23623-23627 (2006).
[cited by applicant]
Tamama et al., Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells 24:686-695 (2006).
[cited by applicant]
Termine et al., Osteonetin, a bone-specific protein linking mineral to collagen. Cell 26:99-105 (1981).
[cited by applicant]
Tokumaru et al., Ectodomain shedding of epidermal growth factor receptor ligands is required for keratinocyte migration in cutaneous wound healing. Journal of Cell Biology 151(2):209-219 (2000).
[cited by applicant]
Traverse et al., EGF triggers neuronal differentiation of PC12 cells that overexpress the EGF receptor. Curr Biol., 4(8):694-701 (1994).
[cited by applicant]
Tzahar et al., A hierarchical network of interreceptor interactions determines signal transduction by neu differentiation factor/neuregulin and epidermal growth factor. Molecular and Cellular Biology 16(10):5276-5287 (1…
[cited by applicant]
U.S. Appl. No. 13/991,842 Office Action dated Jul. 1, 2015.
[cited by applicant]
U.S. Appl. No. 13/991,842 Office Action dated Jul. 13, 2017.
[cited by applicant]
U.S. Appl. No. 13/991,842 Office Action dated Nov. 18, 2016.
[cited by applicant]
U.S. Appl. No. 13/991,842 Office Action dated Nov. 21, 2014.
[cited by applicant]
U.S. Appl. No. 16/892,141 Office Action dated Feb. 5, 2021.
[cited by applicant]
U.S. Appl. No. 16/892,141 Office Action dated Oct. 26, 2020.
[cited by applicant]
U.S. Appl. No. 16/892,141 Restriction Requirement dated Jul. 10, 2020.
[cited by applicant]
Wang et al., Epidermal growth factor receptor-deficient mice have delayed primary encochondral ossification because of defective ostcoclast recruitment. Journal of Biological Chemistry 279(51):53848-53856 (2004).
[cited by applicant]
Whaley et al., Selection of peptides with semiconductor binding specificity for directed nanocrystal assembly. Nature 405:665-668 (2000).
[cited by applicant]
Yashima et al., Crystal structure analysis of beta-tricalcium phosphate Ca3(PO4)2 by neutron powder diffraction. Journal of Solid State Chemistry 175(2):272-277 (2003).
[cited by applicant]
Yazici et al., Bi-functional chimeric peptide coatings for improved osteointegration of titanium implants. Minerals, Metals and Materials Society / AIME 2011 Meeting (2011).
[cited by applicant]
Yuca et al., In vitro labeling of hydroxyapatite minerals by an engineered protein. Biotechnology and Bioengineering 108:1021-1030 (2011).
[cited by applicant]
Zeltinger et al., Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. Tissue Engineering 7(5):557-572 (2001).
[cited by applicant]
Zhang et al., Artificial polypeptide scaffold for protein immobilization. J Am Chem Soc. 127:10136-10137 (2005).
[cited by applicant]
Zhang et al.: New Ouabain-Conjugated Peptide Found From Phage Displayed Peptide Library. American Journal of Hypertension, Ltd. 17:619-623.
[cited by applicant]
Ziros et al., The bone-specific transcriptional regulator Cbfal is a target of mechanical signals in osteoblastic cells, Journal of Biological Chemistry 277(26):23934-23941 (2002).
[cited by applicant]
Co-pending U.S. Application No. 202318451003, inventor Alvarez; Luis, filed on Aug. 16, 2023.
[cited by applicant]
Co-pending U.S. Application No. 202318547668, inventors Alvarez; Luis et al., filed on Aug. 23, 2023.
[cited by applicant]
U.S. Appl. No. 63/505,026, filed May 30, 2023 entitled Compositions and Methods for Localization of Immunomodulator Activity; Inventors Park et al.
[cited by applicant]
U.S. Appl. No. 63,598,496, filed Nov. 13, 2023 entitled Living Bioreactor Compositions and Methods of Use; Inventors Alvarez et al.
[cited by applicant]