Claims for Patent: 8,795,147

Summary for Patent: 8,795,147

Title:	Modifying the genetic regulation of bone and cartilage cells and associated tissue by EMF stimulation fields and uses thereof
Abstract:	An apparatus and method to modify the genetic regulation of mammalian tissue, bone, or any combination. The method may be comprised of the steps of tuning at least one predetermined profile associated with at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of predetermined tuned figures of merit is comprised of a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination to said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or plurality of tuned exposure time sequences.
Inventor(s):	Goodwin; Thomas J. (Houston, TX), Shackelford; Linda C. (Webster, TX)
Assignee:	The United States of America as represented by the Administrator of the National Aeronautics and Space Administration (Washington, DC) N/A (N/A)
Application Number:	12/899,815
Patent Claims:	1. A method to modulate an increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family comprising the steps of: tuning at least one predetermined profile of at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said step of tuning is comprised of, providing at least one set of cellular samples in at least one rotating wall vessel; exposing said at least one set of cellular samples to at least one experimental time-varying stimulation field comprising at least one experimental predetermined profile; conducting at least one gene expression analyses of said at least one set of cellular samples; examining and determining an anabolic effect, catabolic effect, or no effect from the results of said at least one gene expression analyses; generating at least one conclusion from said step of examining and determining; comparing said at least one conclusion with predetermined criteria; if said at least one conclusion does not meet said predetermined criteria, adjusting said at least one experimental predetermined profile based on said at least one conclusion and repeating said steps of providing, exposing, conducting, examining and determining, generating, and comparing; and if said at least one conclusion does meet said predetermined criteria, selecting said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or a plurality of tuned exposure time sequences, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through manipulation of at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of tuned predetermined figures of merit is comprised of two or more of the following: a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; controlling said at least one tuned predetermined profile comprised of manipulating said tuned B-Field magnitude to a first value between about 0.6 G to about 200 G and said tuned falling slew rate to a second value between about 2.0 kG/s and about 500.0 kG/s thereby resulting in a controlled at least one tuned time-varying stimulation field comprised of a controlled at least one tuned predetermined profile; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof to said controlled at least one tuned time-varying stimulation field comprised of said controlled at least one tuned predetermined profile for said predetermined tuned exposure time or said plurality of tuned exposure time sequences thereby resulting in said increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family selected from the group consisting of Wnt signaling family, WSP family, forkhead box (FOX) family, sex determining region Y (SRY) SOX family, parathyroid hormone (PTH) family, transforming growth factor (TGF) beta (TGF-.beta.) super family, latent TGF family (ECM), integrin family (Cell Sulfur-Based (SUR): ECM), interleukin (IL) family (cellular cytokine response), thrombospodin family (COMPs), laminin family, proteoglycan family, osteoglycin, collagen family, insulin family, a disintegrin and metalloproteinase (ADAM) family, ADAM with thrombospondin motifs (ADAMTS) family, matrix metallopeptidase (MMP) family, actin family, catenin family, cadherin super family, B-cell lymphoma (BCL) family, calmodulin calcium-modulated gene, calumenin, cathepsin family, clusterin, cytochrome P 450 super family, endoglin, fibrillin family, fibroblast growth factor (FGF) family, leptin, MAP kinase activated protein kinases (MAPKAP) family, MSX homeobox family, NOTCH family, myotilin-myopalladin-palladin family, peroxisome proliferator-activated receptors (PPARA), Platelet Derived Growth Factor (PDGF) family, reticulocalbin, RUNX runt related transcription factors, signal transducer and activator of transcription (STAT) family, SMAD family, stanniocalcin family, SOD super oxide dismutase family, syndecan family, tumor necrosis factor (TNF) super family, AKT/PKB signaling family, and importin family. 2. The method of claim 1, wherein said step of controlling is further comprised of manipulating at least one of the following said plurality of tuned predetermined figures of merit: said tuned rising slew rate, said tuned rise time, said tuned fall time, said tuned frequency, said tuned wavelength, and said tuned duty cycle. 3. The method of claim 1, wherein said at least one set of cellular samples is selected from the group consisting of human chondrocytes, nucleus pulposus, osteoblasts, osteoclasts, and osteocytes as well as associated tissue. 4. The method of claim 1, wherein said step of examining and determining is comprised of: selecting at least one gene or gene family selected from the group consisting of Wnt signaling family, WSP family, forkhead box (FOX) family, sex determining region Y (SRY) SOX family, parathyroid hormone (PTH) family, transforming growth factor (TGF) beta (TGF-.beta.) super family, latent TGF family (ECM), integrin family (Cell Sulfur-Based (SUR): ECM), interleukin (IL) family (cellular cytokine response), thrombospodin family (COMPs), laminin family, proteoglycan family, osteoglycin, collagen family, insulin family, a disintegrin and metalloproteinase (ADAM) family, ADAM with thrombospondin motifs (ADAMTS) family, matrix metallopeptidase (MMP) family, actin family, catenin family, cadherin super family, B-cell lymphoma (BCL) family, calmodulin calcium-modulated gene, calumenin, cathepsin family, clusterin, cytochrome P 450 super family, endoglin, fibrillin family, fibroblast growth factor (FGF) family, leptin, MAP kinase activated protein kinases (MAPKAP) family, MSX homeobox family, NOTCH family, myotilin-myopalladin-palladin family, peroxisome proliferator-activated receptors (PPARA), Platelet Derived Growth Factor (PDGF) family, reticulocalbin, RUNX runt related transcription factors, signal transducer and activator of transcription (STAT) family, SMAD family, stanniocalcin family, SOD super oxide dismutase family, syndecan family, tumor necrosis factor (TNF) super family, AKT/PKB signaling family, and importin family; calculating a fold change for each gene in said selected at least one gene or gene family from the results of said at least one gene expression analyses; and classifying each of said fold change as said anabolic effect, catabolic effect, or no effect. 5. The method of claim 4, wherein said step of generating is comprised of: establishing a relative value for each of said anabolic effect or catabolic effect; comparing each of said relative value in combination; and selecting at least one conclusion comprised of either a substantive net anabolic effect, a substantive net catabolic effect, or no determinative effect. 6. The method of claim 1, wherein said step of exposing is comprised of: providing a stimulation field generator apparatus capable of generating said controlled at least one tuned time-varying stimulation field and located in proximate spatial relationship to said mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof; and generating said controlled at least one tuned time-varying stimulation field through operation of said stimulation field generator apparatus. 7. The method of claim 6, wherein said stimulation field generator apparatus is comprised of: a power source; a control component operably connected to said power source; and a transmission component operably connected to said control component and said power source, wherein in said step of providing a stimulation field generator apparatus in proximate spatial relationship to said mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof, said transmission component is in proximate spatial relationship to said mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof. 8. The method of claim 1, wherein said first value is between about 0.6 G to about 50 G and wherein said step of controlling is further comprised of manipulating said rising slew rate having a third value between about 2.0 kG/s and about 50.0 kG/s. 9. The method of claim 1, wherein said first value is between about 0.6 G to about 50 G and wherein said step of controlling is further comprised of manipulating said rising slew rate having a third value between about 2.5 kG/s and about 15.5 kG/s. 10. The method of claim 9, wherein said first value is about 0.65 G and said at least one tuned predetermined profile is comprised of substantially a square wave. 11. The method of claim 1, wherein said first value is between about 0.6 G to about 100 G. 12. The method of claim 11, wherein second value is between about 2.5 kG/s and about 15.5 kG/s. 13. The method of claim 1, wherein said first value is between about 0.6 G to about 100 G and wherein said step of controlling is further comprised of manipulating said tuned duty cycle having a fourth value between about 65% to about 80%. 14. The method of claim 1, wherein said step of controlling is further comprised of manipulating said tuned frequency having a fifth value between about 9 Hz to about 200 Hz. 15. The method of claim 14, wherein said fifth value is between about 10 Hz to about 16 Hz. 16. The method of claim 1, wherein said predetermined tuned exposure time is from about 1 hour to about 1200 hours. 17. The method of claim 1, wherein said first value is about 0.65 G, and said second value is between about 4.5 kG/s to about 15.5 kG/s, and wherein said step of controlling is further comprised of manipulating: said tuned frequency having a fifth value between about 10 Hz to about 16 Hz, said tuned wavelength having a sixth value between about 250 ms to about 600 ms, and said tuned duty cycle having a fourth value between about 65% to about 80%. 18. A method to modulate an increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family comprising the steps of: tuning at least one predetermined profile of at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through manipulation of at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of tuned predetermined figures of merit is comprised of two or more of the following: a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; controlling said at least one tuned predetermined profile comprised of manipulating, said tuned B-Field magnitude having a first value of about 0.65 G, said tuned falling slew rate having a second value between about 4.5 kG/s to about 15.5 kG/s, said tuned rising slew rate having a third value between about 2.0 kG/s and to about 4.5 kG/s, said tuned frequency having a fifth value between about 10 Hz to about 200 Hz, said tuned wavelength having a sixth value of about 500 ms, said tuned duty cycle having a fourth value between about 65% to about 80%, thereby resulting in a controlled at least one tuned time-varying stimulation field comprised of a controlled at least one tuned predetermined profile; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof to said controlled at least one tuned time-varying stimulation field comprised of said controlled at least one tuned predetermined profile for a tuned exposure time of about 720 hours thereby resulting in said increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family selected from the group consisting of Wnt signaling family, WSP family, forkhead box (FOX) family, sex determining region Y (SRY) SOX family, parathyroid hormone (PTH) family, transforming growth factor (TGF) beta (TGF-.beta.) super family, latent TGF family (ECM), integrin family (Cell Sulfur-Based (SUR): ECM), interleukin (IL) family (cellular cytokine response), thrombospodin family (COMPs), laminin family, proteoglycan family, osteoglycin, collagen family, insulin family, a disintegrin and metalloproteinase (ADAM) family. ADAM with thrombospondin motifs (ADAMTS) family, matrix metallopeptidase (MMP) family, actin family, catenin family, cadherin super family, B-cell lymphoma (BCL) family, calmodulin calcium-modulated gene, calumenin, cathepsin family, clusterin, cytochrome P 450 super family, endoglin, fibrillin family, fibroblast growth factor (FGF) family, leptin, MAP kinase activated protein kinases (MAPKAP) family, MSX homeobox family, NOTCH family, myotilin-myopalladin-palladin family, peroxisome proliferator-activated receptors (PPARA), Platelet Derived Growth Factor (PDGF) family, reticulocalbin, RUNX runt related transcription factors, signal transducer and activator of transcription (STAT) family, SMAD family, stanniocalcin family, SOD super oxide dismutase family, syndecan family, tumor necrosis factor (TNF) super family, AKT/PKB signaling family, and importin family. 19. A method to modulate an increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family comprising the steps of: tuning at least one predetermined profile of at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through manipulation of at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of tuned predetermined figures of merit is comprised of two or more of the following: a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; controlling said at least one tuned predetermined profile comprised of manipulating said tuned B-Field magnitude to a first value between about 0.6 G to about 200 G and said tuned falling slew rate to a second value between about 2.0 kG/s and about 500.0 kG/s thereby resulting in a controlled at least one tuned time-varying stimulation field comprised of a controlled at least one tuned predetermined profile; exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof to said controlled at least one tuned time-varying stimulation field comprised of said controlled at least one tuned predetermined profile for a predetermined tuned exposure time or plurality of tuned exposure time sequences thereby resulting in said increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family selected from the group consisting of Wnt signaling family, WSP family, forkhead box (FOX) family, sex determining region Y (SRY) SOX family, parathyroid hormone (PTH) family, transforming growth factor (TGF) beta (TGF-.beta.) super family, latent TGF family (ECM), integrin family (Cell Sulfur-Based (SUR): ECM), interleukin (IL) family (cellular cytokine response), thrombospodin family (COMPs), laminin family, proteoglycan family, osteoglycin, collagen family, insulin family, a disintegrin and metalloproteinase (ADAM) family, ADAM with thrombospondin motifs (ADAMTS) family, matrix metallopeptidase (MMP) family, actin family, catenin family, cadherin super family, B-cell lymphoma (BCL) family, calmodulin calcium-modulated gene, calumenin, cathepsin family, clusterin, cytochrome P 450 super family, endoglin, fibrillin family, fibroblast growth factor (FGF) family, leptin, MAP kinase activated protein kinases (MAPKAP) family, MSX homeobox family, NOTCH family, myotilin-myopalladin-palladin family, peroxisome proliferator-activated receptors (PPARA), Platelet Derived Growth Factor (PDGF) family, reticulocalbin, RUNX runt related transcription factors, signal transducer and activator of transcription (STAT) family, SMAD family, stanniocalcin family, SOD super oxide dismutase family, syndecan family, tumor necrosis factor (TNF) super family, AKTIPKB signaling family, and importin family, wherein said mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof are localized in a predetermined region of interest; and introducing Vitamin D, Vitamin K, or both to said region of interest. 20. The method of claim 1, further comprising the step of adding a predetermined amplification factor of predetermined value to said tuned B-Field magnitude.

Details for Patent 8,795,147

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2039-03-29