I 1111111111111111 11111 1111111111 111111111111111 IIIII IIIII IIIIII IIII IIII IIII
`US00903 724 7B2
`
`c12) United States Patent
`Simon et al.
`
`(IO) Patent No.:
`(45) Date of Patent:
`
`US 9,037,247 B2
`May 19, 2015
`
`(54) NON-INVASIVE TREATMENT OF
`BRONCHIAL CONSTRICTION
`
`(75)
`
`Inventors: Bruce J. Simon, Mountain Lakes, NJ
`(US); Joseph P. Errico, Green Brook,
`NJ (US); John T. Raffle, Austin, TX
`(US); Steven Mendez, Brookside, NJ
`(US)
`
`(73) Assignee: Electrocore, LLC, Basking Ridge, NJ
`(US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`(21) Appl. No.: 12/859,568
`
`(22) Filed:
`
`Aug. 19, 2010
`
`(65)
`
`Prior Publication Data
`
`Feb. 24, 2011
`US 2011/0046432 Al
`Related U.S. Application Data
`
`23/02 (2013.01); A61H 23/0236 (2013.01);
`A61H 31/00 (2013.01); A61H 39/002
`(2013.01); A61H 2201/123 (2013.01); A61H
`2201/1604 (2013.01); A61H 2201/1609
`(2013.01); A61H 2201/165 (2013.01); A61N
`1/3601 (2013.01); A61N 1/36114 (2013.01);
`A61N 1140 (2013.01); A61N 21006 (2013.01);
`A61N 2102 (2013.01); A61N 510603 (2013.01);
`A61N 510622 (2013.01); A61N 2005/0605
`(2013.01); A61N 2007/0026 (2013.01); A61N
`113758 (2013.01); A61N 113787 (2013.01)
`(58) Field of Classification Search
`USPC ........................................................ 607/42, 2
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`3,946,745 A
`3,949,743 A
`
`3/1976 Hsiang-Lai et al.
`4/1976 Shanbrom
`(Continued)
`
`FOREIGN PATENT DOCUMENTS
`
`(63) Continuation-in-part of application No. 12/408,131,
`filed on Mar. 20, 2009, which is a continuation-in-part
`of application No. 11/591,340, filed on Nov. 1, 2006,
`now Pat. No. 7,747,324.
`
`(60) Provisional application No. 60/736,001, filed on Nov.
`10, 2005, provisional application No. 60/736,002,
`filed on Nov. 10, 2005, provisional application No.
`60/772,361, filed on Feb. 10, 2006, provisional
`application No. 60/814,313, filed on Jun. 16, 2006,
`provisional application No. 60/786,564, filed on Mar.
`28, 2006.
`
`(51)
`
`Int. Cl.
`A61N 1118
`A61N 1136
`
`(2006.01)
`(2006.01)
`(Continued)
`
`(52) U.S. Cl.
`CPC ............ A61N 1136014 (2013.01); A61H 23100
`(2013.01); A61H 23/004 (2013.01); A61H
`
`JP
`WO
`
`10/2009
`2009233024 A
`2/1993
`WO 93/01862
`(Continued)
`OTHER PUBLICATIONS
`Sammon, M. et al. "Bifurcations of the respiratory pattern produced
`with phasic vagal stimulation in the rat". J Appl Physio/7 5: 912-926,
`1993.
`
`(Continued)
`
`Primary Examiner - Brian T Gedeon
`(74) Attorney, Agent, or Firm - Dentons US LLP
`
`ABSTRACT
`(57)
`Devices, systems and methods for treating bronchoconstric(cid:173)
`tion associated with asthma, anaphylaxis or chronic obstruc(cid:173)
`tive pulmonary disease. The treatment comprises transmit(cid:173)
`ting impulses of energy non-invasively to selected nerve
`fibers that are responsible for smooth muscle dilation, such as
`the vagus nerve.
`28 Claims, 17 Drawing Sheets
`
`NS Device 300
`
`Impulse
`Generator
`310
`
`Control
`Unit
`330
`
`Power
`Source
`320
`
`LUMENIS EX1052
`Page 1
`
`

`

`(51)
`
`Int. Cl.
`A61H 23100
`A61H 31/00
`A61H 39/00
`A61N 1140
`A61N2/00
`A61N2/02
`A61N5/06
`A61N 11375
`A61N 11378
`A61H 23/02
`A61N 7/00
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`4,196,737 A
`4,305,402 A
`4,319,584 A
`4,351,330 A
`4,503,863 A
`4,621,642 A
`4,649,935 A
`4,765,322 A
`4,904,472 A
`4,945,910 A
`4,966,164 A
`4,989,604 A
`5,054,486 A
`5,107,835 A
`5,109,846 A
`5,123,413 A
`5,131,409 A
`5,135,480 A
`5,152,286 A
`5,167,235 A
`5,381,796 A
`5,405,362 A
`5,405,366 A
`5,437,291 A
`5,454,840 A
`5,458,141 A
`5,514,175 A
`5,540,730 A
`5,620,463 A
`5,658,322 A
`5,674,205 A
`5,690,692 A
`5,707,400 A
`5,718,662 A
`5,766,124 A
`5,790,586 A
`5,814,078 A
`5,849,026 A
`5,891,182 A
`5,903,516 A
`5,911,218 A
`5,931,806 A
`5,956,501 A
`5,972,026 A
`5,983,131 A
`5,995,873 A
`6,006,134 A
`6,043,273 A
`6,060,454 A
`6,083,249 A
`6,083,255 A
`6,087,394 A
`6,101,412 A
`6,125,301 A
`6,127,410 A
`6,141,589 A
`6,198,970 Bl
`6,200,333 Bl
`6,203,562 Bl
`
`4/1980 Bevilacqua
`12/1981 Katims
`3/1982 McCall
`9/1982 Scarberry
`3/1985 Katims
`11/1986 Chen
`3/1987 Charmillot et al.
`8/1988 Charmillot et al.
`2/1990 Belardinelli et al.
`8/1990 Budyko et al.
`10/1990 Olsen et al.
`2/1991 Fang
`10/1991 Yamada
`4/1992 Thomas
`5/1992 Thomas
`6/1992 Hasegawa et al.
`7/1992 Lobarev et al.
`8/1992 Bannon et al.
`10/1992 Sitko et al.
`12/1992 Seacord et al.
`1/1995 Pompei
`4/1995 Kramer et al.
`4/1995 Fox et al.
`8/1995 Pasricha et al.
`10/1995 Krakovsky et al.
`10/1995 Neil
`5/1996 Kim et al.
`7/1996 Terry, Jr. et al.
`4/1997 Drolet
`8/1997 Fleming
`10/1997 Pasricha et al.
`11/1997 Fleming
`1/1998 Terry, Jr. et al.
`2/1998 Jalinous
`6/1998 Polson
`8/1998 Hilton, Jr. et al.
`9/1998 Zhou et al.
`12/1998 Zhou et al.
`4/1999 Fleming
`5/1999 Green! eaf et al.
`6/1999 DiMarco
`8/1999 Shimada
`9/1999 Brown
`10/1999 Laufer et al.
`11/1999 Weaver et al.
`11/1999 Rhodes
`12/1999 Hill et al.
`3/2000 Duhaylongsod
`5/2000 Duhaylongsod
`7/2000 Familoni
`7/2000 Laufer et al.
`7/2000 Duhaylongsod
`8/2000 Duhaylongsod
`9/2000 Capel
`10/2000 Duhaylongsod
`10/2000 Duhaylongsod
`3/2001 Freed et al.
`3/2001 Laufer
`3/2001 Ohkubo
`
`US 9,037,247 B2
`Page 2
`
`6,212,432 Bl
`6,230,052 Bl
`6,258,087 Bl
`6,272,375 Bl
`6,273,886 Bl
`6,273,907 Bl
`6,283,988 Bl
`6,283,989 Bl
`6,299,633 Bl
`6,325,798 Bl
`6,327,503 Bl
`6,341,236 Bl
`6,342,221 Bl
`6,356,786 Bl
`6,356,787 Bl
`6,363,937 Bl
`6,366,814 Bl
`6,402,744 B2
`6,411,852 Bl
`6,414,018 Bl
`6,423,058 Bl
`6,424,864 Bl
`6,438,423 Bl
`6,440,128 Bl
`6,463,327 Bl
`6,464,697 Bl
`6,485,416 Bl
`6,547,776 Bl
`6,549,808 Bl
`6,562,034 B2
`6,587,719 Bl
`6,609,030 Bl
`6,610,713 B2
`6,629,951 B2
`6,633,779 Bl
`6,656,960 B2
`6,675,047 Bl
`6,676,686 B2
`6,681,136 B2
`6,711,436 Bl
`6,712,074 B2
`6,738,667 B2
`6,743,371 B2
`6,752,765 Bl
`6,755,849 Bl
`6,778,854 B2
`6,819,956 B2
`6,838,429 B2
`6,853,862 Bl
`6,869,402 B2
`6,871,092 B2
`6,871,099 Bl
`6,872,206 B2
`6,885,888 B2
`6,913,616 B2
`6,934,583 B2
`6,937,896 Bl
`6,937,903 B2
`6,957,106 B2
`6,961,622 B2
`6,970,742 B2
`7,044,917 B2
`7,142,910 B2
`7,264,002 B2
`7,292,890 B2
`7,310,552 B2
`7,386,347 B2
`7,396,326 B2
`7,548,779 B2
`7,591,776 B2
`7,657,310 B2
`7,699,768 B2
`7,740,017 B2
`7,744,523 B2
`7,753,847 B2
`2002/0002387 Al
`2002/0010495 Al
`2002/0016344 Al
`2002/0072738 Al
`
`4/2001 Matsuura
`5/2001 Wolff et al.
`7/2001 Edwards et al.
`8/2001 Katzir et al.
`8/2001 Edwards et al.
`8/2001 Laufer
`9/2001 Laufer et al.
`9/2001 Laufer et al.
`10/2001 Laufer
`12/2001 Edwards et al.
`12/2001 Familoni
`1/2002 Osorio et al.
`1/2002 Thorpe et al.
`3/2002 Rezai et al.
`3/2002 Rezai et al.
`4/2002 Hovda et al.
`4/2002 Boveja et al.
`6/2002 Edwards et al.
`6/2002 Danek et al.
`7/2002 Duhaylongsod
`7/2002 Edwards et al.
`7/2002 Matsuura
`8/2002 Rezai et al.
`8/2002 Edwards et al.
`10/2002 Lurie et al.
`10/2002 Edwards et al.
`11/2002 Platt et al.
`4/2003 Gaiser et al.
`4/2003 Gisel et al.
`5/2003 Edwards et al.
`7/2003 Barrett et al.
`8/2003 Rezai et al.
`8/2003 Tracey
`10/2003 Laufer et al.
`10/2003 Schuler et al.
`12/2003 Puskas
`1/2004 Konoplev et al.
`1/2004 Naganuma
`1/2004 Schuler et al.
`3/2004 Duhaylongsod
`3/2004 Edwards et al.
`5/2004 Deno et al.
`6/2004 John et al.
`6/2004 Jensen et al.
`6/2004 Gowda et al.
`8/2004 Puskas
`11/2004 DiLorenzo
`1/2005 Paslin
`2/2005 Marchal et al.
`3/2005 Arnold
`3/2005 Piccone
`3/2005 Whitehurst et al.
`3/2005 Edwards et al.
`4/2005 Rezai
`7/2005 Hamilton et al.
`8/2005 Weinberg et al.
`8/2005 Kroll
`8/2005 Schuler et al.
`10/2005 Schuler et al.
`11/2005 Gilbert
`11/2005 Mann eta!.
`5/2006 Arnold
`11/2006 Puskas
`9/2007 Danek et al.
`11/2007 Whitehurst et al.
`12/2007 Puskas
`6/2008 Chung et al.
`7/2008 Ghiron et al.
`6/2009 Konchitsky
`9/2009 Phillips et al.
`2/2010 Buras
`4/2010 Kishawi et al.
`6/2010 Danek et al.
`6/2010 Epstein
`7/2010 Greenleaf et al.
`1/2002 Naganuma
`1/2002 Freed et al.
`2/2002 Tracey
`6/2002 Edwards et al.
`
`LUMENIS EX1052
`Page 2
`
`

`

`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`2002/0091379 Al
`2002/0099417 Al
`2002/0107515 Al
`2002/0111386 Al
`2002/0116030 Al
`2002/0143373 Al
`2002/0151888 Al
`2002/0183237 Al
`2002/0183682 Al
`2002/0198570 Al
`2002/0198574 Al
`2003/0023287 Al
`2003/0074039 Al
`2003/0093128 Al
`2003/0144572 Al
`2003/0181949 Al
`2003/0216791 Al
`2003/0216792 Al
`2004/0010289 Al
`2004/0029849 Al
`2004/0030368 Al
`2004/0044390 Al
`2004/0059383 Al
`2004/0073278 Al
`2004/0088030 Al
`2004/0088036 Al
`2004/0106954 Al
`2004/0116981 Al
`2004/0122488 Al
`2004/0122489 Al
`2004/0127942 Al
`2004/0127958 Al
`2004/0147969 Al
`2004/0147988 Al
`2004/0162597 Al
`2004/0167580 Al
`2004/0172075 Al
`2004/0172080 Al
`2004/0172084 Al
`2004/0176803 Al
`2004/0176805 Al
`2004/0204747 Al
`2004/0215289 Al
`2004/0220621 Al
`2004/0230251 Al
`2004/0230252 Al
`2004/0243182 Al
`2004/0249416 Al
`2005/0004609 Al
`2005/0004631 Al
`2005/0010263 Al
`2005/0010270 Al
`2005/0015117 Al
`2005/0021092 Al
`2005/0059153 Al
`2005/0065553 Al
`2005/0065562 Al
`2005/0065567 Al
`2005/0065573 Al
`2005/0065574 Al
`2005/0075701 Al
`2005/0075702 Al
`2005/0076909 Al
`2005/0080461 Al
`2005/0090722 Al
`2005/0107829 Al
`2005/0125044 Al
`2005/0143788 Al
`2005/0149146 Al
`2005/0153885 Al
`2005/0159736 A9
`2005/0165456 Al
`2005/0177192 Al
`2005/0182288 Al
`2005/0187579 Al
`
`7/2002 Danek et al.
`7/2002 Naritoku et al.
`8/2002 Edwards et al.
`8/2002 Sekins et al.
`8/2002 Rezai
`10/2002 Courtnage et al.
`10/2002 Edwards et al.
`12/2002 Puskas
`12/2002 Darvish et al.
`12/2002 Puskas
`12/2002 Gumpert
`1/2003 Edwards et al.
`4/2003 Puskas
`5/2003 Freed et al.
`7/2003 Oschman et al.
`9/2003 Whale
`11/2003 Schuler et al.
`11/2003 Levin et al.
`1/2004 Biggs et al.
`2/2004 Schatzberg et al.
`2/2004 Kemenyetal.
`3/2004 Szeles
`3/2004 Puskas
`4/2004 Pachys
`5/2004 Jung, Jr.
`5/2004 Gilbert
`6/2004 Whitehurst et al.
`6/2004 Mazar
`6/2004 Mazar et al.
`6/2004 Mazar et al.
`7/2004 Yomtov et al.
`7/2004 Mazar et al.
`7/2004 Mann eta!.
`7/2004 Stephens
`8/2004 Hamilton et al.
`8/2004 Mann eta!.
`9/2004 Shafer et al.
`9/2004 Stadler et al.
`9/2004 Knudson et al.
`9/2004 Whelan eta!.
`9/2004 Whelan eta!.
`10/2004 Kemenyetal.
`10/2004 Fukui
`11/2004 Zhou et al.
`11/2004 Schuler et al.
`11/2004 Kullok et al.
`12/2004 Cohen
`12/2004 Yun eta!.
`1/2005 Stahmann et al.
`1/2005 Benedict
`1/2005 Schauerte
`1/2005 Laufer
`1/2005 Gerber
`1/2005 Yun eta!.
`3/2005 George et al.
`3/2005 Ben Ezra et al.
`3/2005 Rezai
`3/2005 Lee et al.
`3/2005 Rezai
`3/2005 Rezai
`4/2005 Shafer
`4/2005 Shafer
`4/2005 Stahmann et al.
`4/2005 Stahmann et al.
`4/2005 Perez
`5/2005 Edwards et al.
`6/2005 Tracey
`6/2005 Yun eta!.
`7/2005 Boveja et al.
`7/2005 Yun eta!.
`7/2005 Danek et al.
`7/2005 Mann eta!.
`8/2005 Rezai et al.
`8/2005 Zahara
`8/2005 Danek et al.
`
`US 9,037,247 B2
`Page 3
`
`2005/0216062 Al
`2005/0222628 Al
`2005/0222635 Al
`2005/0222651 Al
`2005/0228054 Al
`2005/0228460 Al
`2005/0234523 Al
`2005/0238693 Al
`2005/0240241 Al
`2005/0245992 Al
`2005/0251213 Al
`2005/0256028 Al
`2005/0261542 Al
`2005/0261747 Al
`2005/0267536 Al
`2005/0277993 Al
`2005/0283197 Al
`2006/0074284 Al
`2006/0100666 Al
`2006/0100671 Al
`2006/0122675 Al
`2006/0135998 Al
`2006/0167498 Al
`2006/0173510 Al
`2006/0178703 Al
`2006/0247683 Al
`2006/0259028 Al
`2006/0259029 Al
`2006/0259030 Al
`2006/0287679 Al
`2007/0027496 Al*
`2007/0060954 Al
`2007/0106337 Al
`2007/0123952 Al
`2007/0150006 Al
`2007/0150024 Al
`2007/0191902 Al
`2007/0225768 Al
`2007/0276449 Al
`2008/0021512 Al
`2008/0027 513 Al
`2008/0045776 Al
`2008/0058892 Al*
`2008/0071329 Al
`2008/0114199 Al
`2008/0177128 Al
`2008/0177190 Al
`2008/0208266 Al *
`2008/0224808 Al
`2008/0288016 Al
`2008/0306325 Al
`2009/0157149 Al
`2009/0177252 Al
`2009/0281593 A9
`2009/0287035 Al
`2010/0004716 Al
`2010/0057154 Al
`2011/0046432 Al
`2011/0213295 Al
`2011/0224749 Al
`2011/0230701 Al
`2012/0283697 Al
`2012/0303080 Al
`
`9/2005 Herbst
`10/2005 Krakousky
`10/2005 Krakovsky
`10/2005 Jung, Jr.
`10/2005 Tatton
`10/2005 Levin et al.
`10/2005 Levin et al.
`10/2005 Whyte
`10/2005 Yun eta!.
`11/2005 Persen et al.
`11/2005 Freeman
`11/2005 Yun eta!.
`11/2005 Riehl
`11/2005 Schuler et al.
`12/2005 Freeman et al.
`12/2005 Mower
`12/2005 Daum et al.
`4/2006 Juola et al.
`5/2006 Wilkinson
`5/2006 Ridder
`6/2006 Libbus et al.
`6/2006 Libbus et al.
`7/2006 DiLorenzo
`8/2006 Besio et al.
`8/2006 Huston
`11/2006 Denek
`11/2006 Utley
`11/2006 Utley
`11/2006 Utley
`12/2006 Stone
`2/2007 Parnis et al.
`3/2007 Cameron
`5/2007 Errico
`5/2007 Strother et al.
`6/2007 Libbus et al.
`6/2007 Leyde et al.
`8/2007 Errico et al.
`9/2007 Dobak, III
`11/2007 Gunter et al.
`1/2008 Knudson et al.
`1/2008 Carbunaru
`2/2008 Fischell et al.
`3/2008 Haefner et al.
`3/2008 Giuntoli et al.
`5/2008 Riehl et al.
`7/2008 Riehl et al.
`7/2008 Libbus et al.
`8/2008 Lesser et al. ...................... 607/2
`9/2008 Ghiron et al.
`11/2008 Amurthur et al.
`12/2008 Burnett et al.
`6/2009 Wahlgren et al.
`7/2009 Craig
`11/2009 Errico et al.
`11/2009 Dietrich et al.
`1/2010 Zimmerling et al.
`3/2010 Dietrich et al.
`2/2011 Simon eta!.
`9/2011 Henley et al.
`9/2011 Ben-David et al.
`9/2011 Simon eta!.
`11/2012 Kim et al.
`11/2012 Ben-David et al.
`
`. ................... 607/42
`
`................. 607/45
`
`FOREIGN PATENT DOCUMENTS
`
`WO 01/89526 Al
`WO
`WO WO 2004/078252 A2
`WO WO 2009/135693
`
`11/2001
`9/2004
`11/2009
`
`OTHER PUBLICATIONS
`
`Sims, H.S. et al. "Assessing the clinical utility of the magnetic stimu-
`lator for measuring response latencies in the laryngeal muscles".
`Otolaryngol Head Neck Surg 1996; 114:761-7.
`Al-Mutawaly, N. et al. "The Effects of Pulse Configuration on Mag-
`netic Stimulation". Journal of Clinical Neurophysiology 20(5):361-
`370, 2003.
`
`LUMENIS EX1052
`Page 3
`
`

`

`US 9,037,247 B2
`Page 4
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Arnold DH, et al. "Clinical measures associated with FEVl in per(cid:173)
`sons with asthma requiring hospital admission". Am J Emerg Med
`2007, 25:425-429.
`Arnold, D. H. et al. "Noninvasive assessment of asthma severity
`using pulse oximeter plethysmograph estimate ofpulsus paradoxus
`physiology". BMC Pulmonary Medicine 2010, 10: 17.
`Aziz et al. "Magnetic Stimulation of Efferent Neural Pathways to the
`Human Oesophagus". Gut 33: S53-S70 (Poster Session F218)
`(1992).
`Aziz, Q. et al. "Esophageal myoelectric responses to magnetic stimu(cid:173)
`lation of the human cortex and the extracranial vagus nerve". Am. J
`Physiol. 267 (Gastrointest. Liver Physiol. 30): G827-G835, 1994.
`Basham, E. et al. "Magnetic Stimulation of Neural Tissue: Tech(cid:173)
`niques and System Design". pp. 293-352, In: Implantable Neural
`Prostheses 1, Devices and Applications, D. Zhou and E. Greenbaum,
`eds., New York: Springer (2009).
`Binks, A.P. et al. "Oscillation of the lung by chest-wall vibration".
`Respiration Physiology 126 (2001) 245-249.
`Black, B. et al. "Basics of voice coil actuators". Power Conversion
`and Intelligent Motion (PCIM) Jul. 1993 44-46.
`Boldea, I. et al. "Linear electric actuators and generators". IEEE
`Transactions on Energy Conversion. vol. 14 Issue:3 (Sep. 1999):
`712-717.
`Bridge, P.D. et al. "A portable device based on the interrupter tech(cid:173)
`nique to measure bronchodilator response in schoolchildren". Eur
`Respir J, 1996, 9, 1368-1373.
`Canning, Brendan J. "Reflex regulation of airway smooth muscle
`tone". J Appl Physiol 101:971-985, 2006.
`Carbunaru, R. et al. "Toroidal coil models for transcutaneous mag(cid:173)
`netic stimulation of nerves". IEEE Transactions on Biomedical Engi(cid:173)
`neering. 48 (No. 4, Apr. 2001): 434-441.
`Datta, A. et al. "Transcranial current stimulation focality using disc
`and ring electrode configurations: FEM analysis". J Neural Eng. 5
`(2008) 163-174.
`Davey. "Magnetic Stimulation Coil and Circuit Design". IEEE
`Transactions on Biomedical Engineering, vol. 47 (No. 11, Nov.
`2000): 1493-1499.
`De Mayo et al. "Breathing type and body position effects on
`sternocleidomastoid and suprahyoid EMG activity". J of Oral Rehab
`2005 32:487-494.
`Faierstein, "Coil Designs for Localized and Efficient Magnetic
`Stimulation of the Nervous System". Ph.D. Dissertation, Department
`of Biomedical Engineering, Case Western Reserve, May 1999. (UMI
`Microform No. 9940153, UMI Company, Ann Arbor MI).
`Goldberger A. et al. "PhysioBank, PhysioToolkit, and PhysioNet:
`Components of a New Research Resource for Complex Physiologic
`Signals". Circulation 101(23):e215-e220.
`Goodwin. "Mechanical chest stimulation as a physiotherapy aid".
`Med. Eng. Phys., 1994, vol. 16, 267-272.
`Gruber, W. et al. "Laser acupuncture in children and adolescents with
`exercise induced asthma". Thorax 2002;57:222-225.
`Haas, F. et al. "Use of Maximum Expiratory Flow-Volume Curve
`Parameters in the Assessment of Exercise-induced Bronchospasm".
`Chest 1993; 103:64-68.
`Hamdy, S. et al. "Long-term reorganization of human motor cortex
`driven by short-term sensory stimulation". Nature Neuroscience 1
`(issue 1, May 1998):64-68.
`Hamdy, S. et al. "Cranial nerve modulation of human cortical swal(cid:173)
`lowing motor pathways". Am. J Physiol. 272 (Gastrointest. Liver
`Physiol. 35): G802-G808, 1997.
`Heimburg et al. "On soliton propagation in biomembranes and
`nerves". PNASvol. 102 (No. 28, Jul. 12, 2005):9790-9795.
`Hill. Stimulation of the vagus nerve and carotid sinus in man. Experi(cid:173)
`mental Physiology (1932) 22, 79-93.
`Homma. "Inspiratory inhibitory reflex caused by the chest wall vibra(cid:173)
`tion in man". Respiration Physiology (1980) 39, 345-353.
`Hovey, C. et al. The Guide to Magnetic Stimulation, The Magstim
`Company Ltd, Spring Gardens, Whitland, Carmarthenshire, SA34
`OHR, United Kingdom, 2006.
`
`Khedr, E. M. eta!. "Electrophysiological study of vocal-fold mobility
`disorders using a magnetic stimulator". European Journal of Neurol(cid:173)
`ogy 2002, 9: 259-267.
`Khedr, E.M. et al. "Dysphagia and hemispheric stroke: A transcranial
`magnetic study". Neurophysiologie Clinique/Clinical Neurophysiol(cid:173)
`ogy (2008) 38, 235-242.
`Kondo, T. et al. "Respiratory-related bronchial rhythmic constric(cid:173)
`tions in the dog with extracorporeal circulation". J Appl Physiol 88:
`2031-2036, 2000.
`Lambert et al. "Smooth muscle dynamics and maximal expiratory
`flow in asthma". J Appl Physiol 99: 1885-1890, 2005.
`Liboff, A.R. "Signal shapes in electromagnetic therapies: a primer".
`pp. 17-37 in: Bioelectromagnetic Medicine (Paul J. Rosch and Marko
`S. Markov, eds.). New York: Marcel Dekker (2004).
`Lopez-Lopez et al. "Magnetorheology for suspensions of solid par(cid:173)
`ticles dispersed in ferro fluids". J Phys.: Condens. Matter 18 (2006)
`S2803-S2813.
`Man et al. "Magnetic stimulation for the measurement of respiratory
`and skeletal muscle function". Eur Respir J2004; 24: 846-860.
`McCarney RW, et al. "Acupuncture for chronic asthma (Review)".
`The Cochrane Library 2009, Issue 3. John Wiley & Sons, Ltd.
`McCarren B, et al. "Vibration and its effect on the respiratory sys(cid:173)
`tem". Australian Journal of Physiotherapy 52: 39-43(2006).
`Merletti et al. "Technology and instrumentation for detection and
`conditioning of the surface electromyographic signal: State of the
`art". Clinical Biomechanics 24 (2009) 122-134.
`Mutch, M et al. "Fractal ventilation enhances respiratory sinus
`arrhythmia". Respiratory Research 2005, 6:41.
`Nilsson, J. et al. "Determining the site of stimulation during magnetic
`stimulation of the peripheral nerve". Electroencephalographs and
`clinical neurophysiology. vol. 85, pp. 253-264, 1992.
`Olney RK, et al. "A comparison of magnetic and electric stimulation
`of peripheral nerves". Muscle Nerve 1990: 13:957-963.
`Pilla. "Mechanisms and therapeutic applications of time varying and
`static magnetic fields". In Barnes F and Greenebaum B (eds), Bio(cid:173)
`logical and Medical Aspects of Electromagnetic Fields. Boca Raton
`FL: CRC Press, 351-411 (2006).
`Rafferty, G. F. et al. "Magnetic phrenic nerve stimulation to assess
`diaphragm function in children following liver transplantation".
`Pediatr Crit Care Med 2001, 2:122-126.
`Rattay F. "Analysis of models for extracellular fiber stimulation".
`IEEE Trans. Biomed. Eng. 36: 676-82 (1989).
`Rattay, F. "The basic mechanism for the electrical stimulation of the
`nervous system". Neuroscience vol. 89, No. 2, pp. 335-346, 1999.
`Rayner, J. et al. "Continuous Noninvasive Measurement of Pulsus
`Paradoxus Complements Medical Decision Making in Assessment of
`Acute Asthma Severity". Chest 2006; 130:754-765.
`Roy et al. "Reduction of TMD pain by high-frequency vibration: a
`spatial and temporal analysis". Pain 101 (2005) 267-274.
`Sawicki, B. et al. "Mathematical Modelling ofVagus Nerve Stimu(cid:173)
`lation". pp. 92-97 in: Krawczyk, A. Electromagnetic Field, Health
`and Environment: Proceedings of EHE '07. Amsterdam, IOS Press,
`2008.
`Shafik, A. "Functional magnetic stimulation of the vagus nerve
`enhances colonic
`transit
`time
`in healthy volunteers". Tech
`Coloproctol (1999) 3:123-12.
`Shannon, H. et al. "Repeatability of physiotherapy chest wall vibra(cid:173)
`tions applied spontaneously breathing adults". Physiotherapy 95
`(2009) 36-42.
`Shapira, M.Y. et al. "Short-term Acupuncture Therapy Is of No Ben(cid:173)
`efit in Patients With Moderate Persistent Asthma". Chest 2002;
`121: 1396-1400.
`Shusterman, V. et al. "Direct Mechanical Stimulation ofBrainstem
`Modulates Cardiac Rhythm and Repolarization in Humans". Journal
`ofElectrocardiology vol. 35 Supplement 2002, pp. 247-256.
`Similowski, T. et al. "Cervical magnetic stimulation: a new painless
`method for bilateral phrenic nerve stimulation in conscious humans".
`J Appl. Physiol. 67(4): 1311-1318, 1989.
`Simon, B. et al. "Vagal Nerve Stimulation for Relief of
`Bronchoconstriction: Preliminary Clinical Data and Mechanism of
`Action". Proceedings p. 119 ofN euromodulation: 2010 and Beyond;
`North American Neuromodulation Society 13th Annual Meeting,
`Dec. 3-6, 2009.
`
`LUMENIS EX1052
`Page 4
`
`

`

`US 9,037,247 B2
`Page 5
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Smith et al. "Vibration anesthesia: A noninvasive method ofreducing
`discomfort prior to dermatologic procedures". Dermatology Online
`Journal 10(2): 1, http://dermatology.edlib.org/ 102/therapy/anesthe(cid:173)
`sia/comite.html.
`Suki, B. et al. "Life-support system benefits from noise". Nature 393
`(1998) 127-128.
`Tekdemir, I. et al. "A clinico-anatomic study of the auricular branch
`of the vagus nerve and Arnold's ear-cough reflex". Surg RadiolAnat
`1998; 20:253-257.
`Tracey. "The inflammatory reflex". Nature vol. 420 (Dec. 19/26,
`2002) 853-859.
`Vekas. "Ferrofluids and Magnetorheological Fluids". Advances in
`Science and Technology vol. 54 (2008) pp. 127-136.
`Wells, J. et al. "Biophysical Mechanisms of Transient Optical Stimu(cid:173)
`lation of Peripheral Nerve". Biophysical Journal vol. 93 Oct. 2007
`2567-2580.
`Whittaker. "Laser acupuncture: past, present, and future". Lasers in
`Medical Science (2004) 19: 69-80.
`Guarini et al., "Efferent Vagal Fibre Stimulation Blunts Nuclear
`Factor-kB Activation and Protects Against Hypovolemic Hemor(cid:173)
`rhagic Shock", Circulation 2003 vol. 107 pp. 1189-1194.
`International Search Report and Written Opinion for corresponding
`PCT application PCT/US2006/42752.
`International Search Report and Written Opinion of the International
`Searching Authority dated Mar. 16, 2007 oflnternational Application
`No. PCT/US2006/042823, International filing date Nov. 2, 2006.
`International Search Report and Written Opinion of the International
`Searching Authority dated Jun. 2, 2007 of International Application
`No. PCT/US2006/42828, International filing date Nov. 2, 2006.
`
`International Search Report and Written Opinion of the International
`Searching Authority dated May 20, 2009 oflnternational Application
`No. PCT/US2009/038081, International filing date Mar. 24, 2009.
`International Search Report and Written Opinion of the International
`Searching Authority dated Jan. 29, 2008 oflnternational Application
`No. PCT/US06/42752, International filing date Nov. 1, 2006.
`Supplemental European Search Report for EP Application No.
`06827343,Aug.21,2009.
`Supplemental European Search Report for EP Application No.
`06827386.1, Aug. 21, 2009.
`U.S. Appl. No. 60/206,364, Title: Vagus Nerve Stimulation Attenu(cid:173)
`ation of the Systemic Inflammatory Response to Endotoxin, filed
`May 23, 2000, Inventor: Tracey.
`International Search Report and Written Opinion of the International
`Searching Authority dated Dec. 3, 2011, PCT application PCT/
`USl 1/47509, International Filing Date Aug. 12, 2011.
`International Search Report and Written Opinion of the International
`Searching Authority dated Dec. 22, 2011, PCT application PCT/
`USl 1/49844, International Filing Date Aug. 30, 2011.
`Eriksson, Thomas. A Finite Element Study of the Electrode Configu(cid:173)
`ration for Nerve Conduction Block. Master's Thesis in Computer
`Science at the School of Microelectronics Royal Institute of Tech(cid:173)
`nology. 2008. Stockholm, Sweden.
`International Search Report and Written Opinion dated Dec. 22, 2011
`in related PCT Application No. PCT/US201 l/049844 filed Aug. 31,
`2011 (9 pages).
`International Search Report and Written Opinion dated Apr. 30, 2013
`in related PCT Application No. PCT/US2013/023014 filed Jan. 24,
`2013 (7 pages).
`
`* cited by examiner
`
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`U.S. Patent
`
`May 19, 2015
`
`Sheet 1 of 17
`
`US 9,037,247 B2
`
`350
`
`FIG. 1
`
`NS Device
`
`Generator
`310
`
`Control
`Unit
`330
`
`Power
`Source
`320
`
`FIG. 2
`
`400
`
`Activity
`
`Current
`
`Pulses
`410
`
`Time
`
`420
`
`Current
`
`I
`
`;
`
`410
`
`,---
`
`Time
`
`LUMENIS EX1052
`Page 6
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`

`

`U.S. Patent
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`May 19, 2015
`
`Sheet 2 of 17
`
`US 9,037,247 B2
`
`FIG. 3
`
`Linear Actuator 540
`
`NS Device 500
`
`Impulse
`Generator
`510
`
`Control
`Unit
`530
`
`Power
`Source
`520
`
`LUMENIS EX1052
`Page 7
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`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 3 of 17
`
`US 9,037,247 B2
`
`NS Device 800
`
`FIG. 4
`
`Gene rat.or
`810
`
`Control
`Unit
`830
`
`Power
`Source
`820
`
`Light-Emitting Earplug
`860
`
`866'\
`~w864 ~
`LI~
`868
`862
`
`854
`Light
`\. Modulator
`850
`
`Laser 840
`
`\
`844
`
`LUMENIS EX1052
`Page 8
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`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 4 of 17
`
`US 9,037,247 B2
`
`FIG. 5
`
`BP
`
`HR
`
`FIG. 6
`
`BP
`
`LUMENIS EX1052
`Page 9
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 5 of 17
`
`US 9,037,247 B2
`
`BP
`
`FIG. 7
`
`FIG. 8
`
`LUMENIS EX1052
`Page 10
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 6 of 17
`
`US 9,037,247 B2
`
`BP
`
`FIG. 9
`
`FIG. 10
`
`LUMENIS EX1052
`Page 11
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 7 of 17
`
`US 9,037,247 B2
`
`FIG. 11
`
`BP
`
`FIG. 12
`
`LUMENIS EX1052
`Page 12
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 8 of 17
`
`US 9,037,247 B2
`
`FIG. 13
`
`BP
`
`FIG. 14
`
`LUMENIS EX1052
`Page 13
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 9 of 17
`
`US 9,037,247 B2
`
`FIG. 15
`
`Stimulation at 7 V
`
`100
`
`95
`
`90 -'"O
`
`85
`
`80
`
`75
`
`(1)
`.......,
`(.)
`'"O
`,._
`(1)
`CL
`'+-
`0
`--.,.... 65
`'2ft.
`> w
`
`70
`
`•
`
`LL
`
`60
`
`I electrode removed
`
`electrode inserted
`
`55
`
`50
`
`0
`
`50
`
`100
`
`150
`
`200
`250
`Time (min)
`
`300
`
`350
`
`400
`
`450
`
`LUMENIS EX1052
`Page 14
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 10 of 17
`
`US 9,037,247 B2
`
`FIG. 16
`
`---FEV
`--e- Heart Rate
`---4:--- MAP/ 1 .4
`
`90
`
`85
`
`i 80
`
`:::,
`:!::::
`Cl.
`E
`<( 75
`
`70
`
`65----.---.----r----r----r----r-----r-----r~~---,---,.---,---~~-r--r-----,
`50
`1 00
`150
`200
`250
`300
`350
`400
`450
`0
`Time (min)
`
`LUMENIS EX1052
`Page 15
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 11 of 17
`
`US 9,037,247 B2
`
`FIG. 17
`
`Methacholine Challenge
`
`....
`, .~
`~
`~
`~ V
`
`!
`I
`I
`7
`I
`..,
`...,
`
`3.8
`
`3.6
`
`3.4
`
`3.2
`
`3
`
`.,..
`1l:i
`LL 2.8
`
`2.6
`
`2.4
`
`2.2
`
`2
`
`....
`
`T
`
`<:)
`
`LUMENIS EX1052
`Page 16
`
`

`

` N
`
`�-:а'N�-:а =
`
`
`cj00\С
`
`.....
`
`
`
`..........:i
`
`Q
` N
`
`-....
`
`=­�
`
` �
`rFJ
`
`U1
`....
`
`с:>
`N
`
`....
`
`�
`�
`
`�
`� ��
`�
`
`�
`
`45.0
`
`105.0
`
`349
`
`59.З
`
`Average
`
`12% FEV1
`
`increase
`
`15
`
`Elapsed Тlme untll
`
`Peek FEV1 Jncreue
`Elapsed Tln1e (rnin) to
`
`90
`150
`75
`FEV1 from lnl tlal
`Peak % lncrease
`
`19.7
`
`41
`43.9
`
`HJstoric.ar
`
`FEV1 % Predicted
`
`01-002
`01-001
`03-001
`Patient ID FEV1 % Predicted
`Da:te minus patient 04-001 iil'ld 04-002
`
`66
`
`S1
`
`61
`IПttlll
`
`90
`
`33.0
`
`96.0
`
`51.1
`
`49.2
`
`Avera_ae
`
`12% Fl!!V 1 lncreue
`Etll)Qi Time unlil
`
`to
`
`15
`90
`15
`30
`16
`Peat lncrease
`Elapsed Tinte (min)
`
`fEV., l'rom lnltlll
`Pealk % lncrease
`
`15
`90
`150
`150
`75
`
`19.2
`19.7
`131.3
`41.2
`4:,Ц)
`
`Historlcal
`
`FEV1 % Pпdicted
`
`52
`66
`16
`51
`61
`FEV1 % Predicted
`lnitial
`
`01�001
`03--001
`Patient 10
`
`FIG. 18
`
`LUMENIS EX1052
`Page 17
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 13 of 17
`
`US 9,037,247 B2
`
`FIG. 19
`
`FIG. 20
`
`LUMENIS EX1052
`Page 18
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`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 14 of 17
`
`US 9,037,247 B2
`
`BP
`
`FIG. 21
`
`HR
`
`FIG. 22
`
`HR
`
`LUMENIS EX1052
`Page 19
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 15 of 17
`
`US 9,037,247 B2
`
`BP
`
`FIG. 23
`
`HR
`
`BP
`
`FIG. 24
`
`LUMENIS EX1052
`Page 20
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 16 of 17
`
`US 9,037,247 B2
`
`LO
`N
`■ (9
`LL
`
`LUMENIS EX1052
`Page 21
`
`

`

`U.S. Patent
`
`May 19, 2015
`
`Sheet 17 of 17
`
`US 9,037,247 B2
`
`(0
`N
`■ (9
`LL
`
`LUMENIS EX1052
`Page 22
`
`

`

`US 9,037,247 B2
`
`1
`NON-INVASIVE TREATMENT OF
`BRONCHIAL CONSTRICTION
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`The present application is a continuation-in-part of U.S.
`patent application Ser. No. 12/408,131 filed Mar. 20, 2009,
`which is a continuation-in-part ofU.S. patent application Ser.
`No. 11/591,340 filed Nov. 1, 2006, now U.S. Pat. No. 7,747,
`324 issued Jun. 29, 2010, which claims the benefit of U.S.
`Provisional Application Nos. 60/786,564 filed Mar. 28, 2006;
`60/814,313 filed Jun. 16, 2006; 60/772,361 filed Feb. 10,
`2006; 60/736,001 filed Nov. 10, 2005 and 60/736,002 filed
`Nov. 10, 2005, each of which is incorporated herein by ref(cid:173)
`erence in its entirety.
`
`BACKGROUND OF THE INVENTION
`
`The field of the present invention relates to the delivery of
`energy impulses ( and/or fields) to bodily tissues for therapeu(cid:173)
`tic purposes, and more specifically to non-invasive devices
`and methods for treating conditions associated with bronchial
`constriction. The energy impulses (and/or fields) comprise
`electrical and/or magnetic, mechanical and/or acoustic, and
`optical and/or thermal energy.
`There are a number of treatments for various infirmities
`that require the destruction of otherwise healthy tissue in
`order to affect a beneficial effect. Malfunctioning tissue is
`identified, and then lesioned or otherwise compromised in
`order to affect a beneficial outcome, rather than attempting to
`repair the tissue to its normal functionality. While there are a
`variety of different techniques and mechanisms that have
`been designed to focus lesioning directly onto the target nerve
`tissue, collateral damage is inevitable.
`Still other treatments for malfunctioning tissue can be
`medicinal in nature, in many cases leaving patients to become
`dependent upon artificially synthesized chemicals. Examples
`of this are anti-asthma drugs such as albuterol, proton pump
`inhibitors such as omeprazole (Prilosec ), spastic bladder 40
`relievers such as Ditropan, and cholesterol reducing drugs
`like Lipitor and Zocor. In many cases, these medicinal
`approaches have side effects that are either unknown or quite
`significant. For example, at least one popular diet pill of the
`late 1990' s was subsequently found to cause heart attacks and 45
`strokes. Unfortunately, the beneficial outcomes of surgery
`and medicines are, therefore, often realized at the cost of
`function of other tissues, or risks of side effects.
`The use of electrical stimulation for treatment of medical
`conditions has been well kuown in the art for nearly two
`thousand years. It has been recognized that electrical stimu(cid:173)
`lation of the brain and/or the peripheral nervous system and/
`or direct stimulation of the malfunctioning tissue, which
`stimulation is generally a wholly reversible and non-destruc(cid:173)
`tive treatment, holds significant promise for the treatment of
`many ailments.
`Electrical stimulation of the brain with implanted elec(cid:173)
`trodes has been approved for use in the treatment of various
`conditions, including pain and movement disorders including
`essential tremor and Parkinson's disease. The principle
`behind these approaches involves disruption and modulation
`of hyperactive neuronal circuit transmission at specific sites
`in the brain. As compared with the very dangerous lesioning
`procedure