WO2009135142A1 - Electrode lead system - Google Patents

Electrode lead system Download PDF

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Publication number
WO2009135142A1
WO2009135142A1 PCT/US2009/042546 US2009042546W WO2009135142A1 WO 2009135142 A1 WO2009135142 A1 WO 2009135142A1 US 2009042546 W US2009042546 W US 2009042546W WO 2009135142 A1 WO2009135142 A1 WO 2009135142A1
Authority
WO
WIPO (PCT)
Prior art keywords
lead
nerve
lead portion
cuff
anchor
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2009/042546
Other languages
English (en)
French (fr)
Inventor
Eric H. Bonde
Roy L. Testerman
Timothy P. Herbert
Mark A. Christopherson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medtronic Inc
Original Assignee
Medtronic Inc
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 Medtronic Inc filed Critical Medtronic Inc
Priority to AU2009242504A priority Critical patent/AU2009242504A1/en
Priority to EP09739944.8A priority patent/EP2310084B1/en
Priority to CA2722987A priority patent/CA2722987A1/en
Priority to US12/990,705 priority patent/US20110160827A1/en
Priority to JP2011507688A priority patent/JP5538367B2/ja
Priority to CN2009801256760A priority patent/CN102202726A/zh
Publication of WO2009135142A1 publication Critical patent/WO2009135142A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551Spinal or peripheral nerve electrodes
    • A61N1/0556Cuff electrodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551Spinal or peripheral nerve electrodes
    • A61N1/0558Anchoring or fixation means therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526Head electrodes

Definitions

  • the present disclosure relates generally to an implantable stimulation system for stimulating and monitoring soft tissue in a patient, and more particularly, the present disclosure relates to a lead system for positioning an electrode and lead body of an implantable stimulation system within a body.
  • Sleep apnea generally refers to the cessation of breathing during sleep.
  • One type of sleep apnea referred to as obstructive sleep apnea (OSA)
  • OSA obstructive sleep apnea
  • One treatment for obstructive sleep apnea has included the delivery of electrical stimulation to the hypoglossal nerve, located in the neck region under the chin. Such stimulation therapy activates the upper airway muscles to maintain upper airway patency.
  • increased respiratory effort resulting from the difficulty in breathing through an obstructed airway is avoided by synchronized stimulation of an upper airway muscle or muscle group that holds the airway open during the inspiratory phase of breathing.
  • the genioglossus muscle is stimulated during treatment of sleep apnea by a cuff electrode place around the hypoglossal nerve.
  • a related challenge in maintaining the proper positioning of the electrode includes making a proper placement of a lead body that extends from the electrode to an implantable pulse generator, which is typically located in the pectoral region of the patient.
  • FIG. 1 is a schematic diagram of an implantable stimulation system, according to an embodiment of the present disclosure
  • FIG. 2 is a side view of a lead system utilized in an implantable stimulation system, according to an embodiment of the present disclosure
  • FIG. 3 is a perspective view of an expandable cuff electrode, according to an embodiment of the present disclosure.
  • FIG. 4 is a sectional view of the cuff electrode as taken along lines 4 — 4 of Figure 3, according to an embodiment of the present disclosure
  • FIG. 5 is a sectional view of an expandable electrode cuff in a larger diameter, fully engaged position, according to an embodiment of the present disclosure; 1618.111.101
  • FlG. 6 is a side plan view of a lead assembly including a cuff electrode and a lead body, according to an embodiment of the present disclosure.
  • FIG. 7 is plan view schematically illustrating deployment of the lead assembly of FIG. 6, according to an embodiment of the present disclosure.
  • Embodiments of the present disclosure provide a lead system including a cuff electrode configured to be secured on a nerve and a lead body extending from the cuff electrode to connect with an implantable pulse generator located remotely from the location of the nerve.
  • the lead body includes a first lead portion, an anchor, and a second lead portion.
  • the anchor is secured relative to a non-nerve anatomical structure, such as a tendon, in close proximity to the location of the cuff electrode on the nerve.
  • the first lead body is configured with a length substantially greater than a distance between the secured cuff electrode and the secured anchor.
  • the first lead portion includes a generally serpentine configuration formed of a resilient material.
  • a strain relief mechanism is established to prevent the cuff electrode from being dislodged from the nerve, or from placing undue stress on the nerve, on the cuff electrode, and/or on the lead body.
  • FIG. 1 is a schematic diagram of an implantable stimulation system 12, according to an embodiment of the present disclosure.
  • an example of an implantable stimulation system 12 includes an implantable pulse generator (IPG) 55, capable of being surgically positioned within a pectoral region of a patient 10, and a stimulation lead 52 electrically coupled with the IPG 55 via a connector (not shown) positioned within a connection port of the IPG 55.
  • the lead 52 includes an electrode or electrode system 65 and extends from the IPG 55 so that the electrode system 65 is position around a desired nerve, such as the hypoglossal nerve 53 of the patient 10, to enable stimulation of the nerve 53, as described below in detail.
  • lead 52 may be utilized, for example, is described in U.S. Patent No. 6,572,543 to Christopherson et al., incorporated herein by reference in its entirety, and further includes a sensor lead 57 electrically coupled to the IPG 55 and extending from the IPG 55 so that a sensor or transducer 60 can be positioned in the patient 10 for sensing of respiratory effort.
  • the sensor 60 may be a pressure sensor that is surgically implanted in a region that has pressure continuity with the intrapleural space, such as the suprasternal notch, the space between the trachea and esophagus, or by being attached to either of the trachea or esophagus.
  • the sensor 60 may also be positioned intercostally, or secured in a position for sensing pressure at the posterior side of the manubrium.
  • the suprasternal notch 62 and manubrium 63 of the sternum 64 are well known structures on the upper chest that are in anatomical continuity with the intrapleural space. It is also well known that 1618.111.101
  • the location for placement of the sensor 60 is, at least in part, chosen as a function of a delay, i.e. the propagation time associated with a pressure waveform characteristic of respiratory effort propagating from the respiratory point of origin to the sensor position.
  • the chosen location is also a function of the amount of filtering necessary to achieve a usable sensed signal at a particular location, i.e. the amount of filtering that is necessary to remove waveforms other than the waveform associated with the desired sensed characteristic, such as the filtering required to remove cardiac waveform activity, for example.
  • the positioning of the sensor 60 enables the IPG 55 to receive respiratory effort waveform information utilized to determine increased respiratory effort, which is then used by the IPG 55 to control delivery of therapy in response to determined increases in respiratory effort.
  • FIG. 2 is a side view of a lead system 80 utilized in the implantable stimulation system, according to an embodiment of the present disclosure, with lead system 80 being used in place of lead 52 of FIG. 1.
  • the lead system 80 includes a lead body 82, connector 88, and an expandable cuff electrode 90.
  • the lead body 82 extends from a proximal end 84 to a distal end 86, with the connector 88 being positioned at the proximal end 84 of the lead body 82 for electrically connecting the lead body 82 to the IPG 55.
  • the expandable electrode cuff 90 is located at the distal end 86 of the lead body 82 and is configured to be positioned around a target nerve, such as a hypoglossal nerve or other nerve.
  • the electrode cuff 90 includes one or more electrodes 92 embedded within a wall of the electrode cuff 90 so that when the electrode cuff 90 is positioned around the nerve, the respective electrodes 92 are in contact with the nerve.
  • the lead body 82 includes conductors (not shown) extending within the lead body 82 to electrically connect the electrodes 92 and the connector 88 so that the electrodes 92 are electrically 1618.111.101
  • FIG. 3 is a perspective view of an expandable electrode cuff 100, according to one embodiment of the present disclosure, which can be deployed in place of the cuff electrode 90 in lead system 80.
  • cuff 100 includes a cuff body 101 and an array 102 of electrodes 103.
  • the cuff body 101 defines a lumen 140 through which a target nerve will extend.
  • the cuff body 101 includes a pair of resilient fingers 134, 150 (e.g., flange members) that have a generally arcuate shape and that extend from a base portion 120 of cuff body 101.
  • the cuff body 101 resumes the shape illustrated in FIG. 3.
  • the materials and construction of the fingers 134, 150 permit automatic expansion of the size of lumen 140 to accommodate expansion of the size of the nerve encircled by the cuff body 101.
  • the electrodes 103 are held in close contact against the nerve while allowing for expansion of a diameter of lumen 140 defined between fingers 134, 150 and base 120.
  • the array 102 of electrodes 103 are embedded within a wall of the cuff body 101 with the respective electrodes 103 spaced apart from each other along a length of the cuff body 101.
  • the electrodes 103 are aligned in series along a single longitudinal axis on a common side or portion of the cuff body 101.
  • cuff 100 additionally includes an outer flap or flange member that is biased and configured to maintain releasable coverage of at least a portion of an outer surface of the cuff body 101 and of the re-closable opening 109 between the distal ends of fingers 134, 150, as will be described in more detail in association with at least Figures 4-5.
  • an outer flap or flange member that is biased and configured to maintain releasable coverage of at least a portion of an outer surface of the cuff body 101 and of the re-closable opening 109 between the distal ends of fingers 134, 150, as will be described in more detail in association with at least Figures 4-5.
  • 1618.111.101 in other 1618.111.101
  • this outer flap is omitted.
  • Figure 3 illustrates cuff body 101 without an outer flap for illustrative clarity in viewing the features and attributes of cuff body 101 that would otherwise be obscured by the presence of an outer flap.
  • FIG. 4 is a sectional view of the expandable electrode cuff 100, as taken along lines 4 — 4 of FIG. 3, according to an embodiment of the present disclosure.
  • the cuff body 101 of the expandable electrode cuff 100 includes a base portion 120, a first flange member 130, a second flange member 134, and a third flange member 150.
  • FIG. 4 also illustrates one of the electrodes 103 that is embedded in cuff body 101 , as previously illustrated in FIG. 3.
  • electrode 103 includes a proximal trunk portion 110, a body portion 111 , and a distal hook portion 112 with the distal hook portion 112 defining a recess 114 that extends between a distal tip portion 115 and body portion 111.
  • the proximal trunk portion 110 extends within, and is embedded within, the base portion 120 of the cuff body 101 while the body portion 111 is embedded within the second flange member 134 to be exposed within lumen 140.
  • the base portion 102 includes a top wall 122, a bottom wall 124, a first side wall 126, and a second side wall 128.
  • the second flange member 134 and the third flange member 150 comprise arcuate shaped fingers that are shaped, biased, and have a length to define a generally circular shaped lumen 140.
  • the second flange member 134 extends generally outward from the second side wall 128 and from the top wall 122 of the base portion 120 with at least a portion of the second flange member 134 being spaced apart from the top wall 122 of the base portion 120.
  • the third flange member 150 extends generally outward from the first side wall 126 and from the top wall 122 of the base portion 120.
  • the first flange member 130 includes a proximal end 131 and a distal end or portion 132 with the proximal end 131 being bonded 1618.111.101
  • the first flange member 130 has a length sufficient to extend about, and be in releasable contact with, the periphery or outer surface of both the third flange member 150 and a majority of a length of the second flange member 134.
  • the first flange member 130 is biased to maintain coverage across the substantially re-closable opening 109 (between the distal ends 136, 152 of the respective second and third flange members 134, 150).
  • the free distal portion (including distal end 132) of the first flange member 130 extends in a first direction or orientation opposite to the direction (or orientation) in which the free distal portion (including distal end 136) of the second flange member 134 extends.
  • each of the distal ends 132, 136 of the respective first and second flange members 130, 134 will move in opposite directions upon expansion of the lumen 140 in response to a swollen nerve or during positioning of the cuff 100 about a nerve, as will be further described in association with at least FIG. 5.
  • the electrode cuff 100 is in a fully engaged position (shown in FIG. 4). Together, the distal ends 136, 152 of the respective second and third flange members 134, 150 form the substantially re-closable opening 109 that provides selective access to lumen 140 and that generally maintains a nerve securely within the lumen 140, unless affirmative steps are taken to remove the electrode cuff 100 from the nerve.
  • the electrode cuff 100 may be either in the fully engaged position of FIG. 5 or in a 1618.111.101
  • FIG. 5 the general configuration of the electrode cuff 100 remains generally the same as the fully engaged position except that, because the first flange member 130 is slidably movable relative to the second flange member 134 and because the generally flexible, distal portion of the second flange member 134 permits rotational movement of the second flange member 134 away from the third flange member 150, the distal end 132 of the first flange member 130 will be positioned along the outer side wall 146 of the second flange member 134 in a location spaced further away from the second side wall 128 than shown in FIG.
  • the substantially re-closable opening 109 between the distal end 136 of the second flange member 134 and the distal end 152 of the third flange member 150 will at least partially open as a gap between the distal ends 136, 152, as shown in FIG. 5. Nevertheless, despite this gap, in the partially fully engaged position the lumen 140 remains generally closed because the first flange member 130 has a length sufficient to still extend across the gap (in the substantially re-closable opening 109) between the respective distal ends 136, 152 and to extend further over (and in releasable contact with) substantial remaining portions of the second flange member 134.
  • FIG. 6 is a side plan view of a lead system, according to an embodiment of the present disclosure.
  • the lead system 200 comprises a cuff electrode 202, a first lead portion 204, a second lead portion 208, an anchor 206, and a connector 210.
  • the cuff electrode 202 of lead system 850 comprises a cuff electrode having substantially the same features and attributes as the embodiments of cuff electrode 100, as previously described in association with FIGS. 2-5.
  • the cuff electrode 202 comprises other features and attributes of conventional electrode cuffs. 1618.111.101
  • the first lead portion 204 extends proximally from the cuff electrode 202 and is formed of a resilient material to have a pre-formed, generally serpentine configuration.
  • the second lead portion 208 also is formed of a resilient material to have a pre-formed, generally serpentine configuration.
  • the second lead portion 208 has a length substantially greater than a length of the first lead portion 204.
  • the second lead portion 208 has a length about seven times the length of the first lead portion 204.
  • the second lead portion 208 has a length sufficient to extend from the placement location of the cuff electrode 202 at a target nerve (e.g. hypoglossal nerve) to the location of placement of the IPG 55 (FIG. 1) within a pectoral region.
  • a target nerve e.g. hypoglossal nerve
  • the generally serpentine configuration of the respective first and second lead portions 204, 208 comprises a generally sinusoidal pattern including a series of S-shaped curves.
  • the generally serpentine configuration of the respective first and second lead portions 204, 208 comprises other undulating or curvaceous shapes and patterns.
  • a respective one of the first and second lead portions 204, 208 has a first type of undulating or curvaceous pattern while the other respective one of the first and second lead portions 204, 208 have a second, different type of undulating or curvaceous pattern.
  • the anchor 206 is interposed between the first lead portion and the second lead portion 208 and is configured to be secured relative to a body structure adjacent to the target nerve on which the cuff electrode 202 is mounted.
  • the connector 210 extends proximally from the second lead portion 208 and is configured to electrically connect to an implantable pulse generator (such as IPG 55 in FIG. 1).
  • the first anchor 204 is not accompanied by a second anchor along the lead body. 1618.111.101
  • the lead system 200 additionally includes a second anchor interposed between the second lead portion 208 and the connector 210 at a location represented by reference numeral 220 (or another location closer to the first anchor 204).
  • This second anchor is configured to be secured relative to a body structure and is provided to provide strain relief for the lead system relative to the IPG 55 and relative to the first anchor 204 (when it is secured in close proximity to the cuff electrode and nerve).
  • FIG. 7 schematically illustrates a method 300 of placing or delivering the lead assembly 850.
  • the method 300 comprises first providing a lead assembly such as lead assembly 200 as previously described in association with FIG. 6.
  • the first lead portion 204 is maneuvered and arranged to extend proximally from the cuff electrode 202 to a non-nerve bodily structure 330 (such as a digastric tendon, other tendon, or bony structure) that is in close proximity to the hypoglossal nerve 310 and through the mylohyoid muscle (not shown).
  • a non-nerve bodily structure 330 such as a digastric tendon, other tendon, or bony structure
  • the first anchor 206 is secured the anchor (via sutures 333 or other biocompatible fasteners) to the non-nerve bodily structure 330 adjacent the target nerve 310 while maintaining at least a portion 341 of the first lead portion 204 in a generally serpentine or undulating configuration between the cuff electrode 202 and the anchor 206. In this arrangement, other portions 340 of the first lead portion 204 are no longer retain their pre-formed generally serpentine shape.
  • method 300 includes arranging the secured cuff electrode 202 and the secured anchor 206 in substantially the same vertical plane such that a majority of the first lead portion 204 extends generally perpendicular to the vertical plane. In one aspect, this arrangement helps to provide the strain relief described below in more detail. 1618.111.101
  • the second lead portion 208 is then maneuvered and arranged to extend proximally from the anchor toward an implantable pulse generator, using tunneling tools as known in the art. Finally, the connector is used to establish electrical communication and mechanical connection to the IPG 55.
  • the first lead portion 204 has an arcuate length (L1) of about three inches and an at-rest, end-to-end length (L2) of about one inch.
  • the arcuate length corresponds to the length of the first lead portion 204 from end-to-end if the first lead portion 204 were stretched out to eliminate the curved portions.
  • the end-to-end length (L2) corresponds to the length of the first lead portion 204 from its proximal end (at anchor 206) to its distal end (at cuff electrode 202) without accounting for the length of the curved portions between the respective ends of the first lead portion 204.
  • the first lead portion 204 has other lengths greater or less than the above-described dimensions provided that the selected length is substantially greater than an expected degree of movement or range of motion of the target nerve 310 relative to the adjacent non-nerve anatomical structure 330. 1618.111.101
  • the second lead portion 208 has an arcuate length (L3) of about ten to twelve inches (i.e., including the length of the curved portions) and an end-to-end length (i.e., excluding the length of the curved portions) of about seven inches.
  • the second lead portion 208 has other lengths greater or less than the above- described dimensions provided that the selected length is sufficiently long to provide compensate for some degree of bodily movement between the point at which anchor 206 is fastened and the location of the IPG 55 (FIG. 1) .
  • Embodiments of the present disclosure ensure long term, robust deployment of a cuff electrode on a nerve via a lead system.
  • this robust engagement is accomplished via placing a relatively long, generally serpentine lead portion between the secured cuff electrode and an anchor secured to a non-nerve anatomical structure close to the cuff electrode and nerve.

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  • Health & Medical Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Electrotherapy Devices (AREA)
  • Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
PCT/US2009/042546 2008-05-02 2009-05-01 Electrode lead system Ceased WO2009135142A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
AU2009242504A AU2009242504A1 (en) 2008-05-02 2009-05-01 Electrode lead system
EP09739944.8A EP2310084B1 (en) 2008-05-02 2009-05-01 Electrode lead system
CA2722987A CA2722987A1 (en) 2008-05-02 2009-05-01 Electrode lead system
US12/990,705 US20110160827A1 (en) 2008-05-02 2009-05-01 Electrode lead system
JP2011507688A JP5538367B2 (ja) 2008-05-02 2009-05-01 電極リードシステム
CN2009801256760A CN102202726A (zh) 2008-05-02 2009-05-01 电极引线系统

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4992708P 2008-05-02 2008-05-02
US61/049,927 2008-05-02

Publications (1)

Publication Number Publication Date
WO2009135142A1 true WO2009135142A1 (en) 2009-11-05

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Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2009/042546 Ceased WO2009135142A1 (en) 2008-05-02 2009-05-01 Electrode lead system
PCT/US2009/042539 Ceased WO2009135138A1 (en) 2008-05-02 2009-05-01 Self expanding electrode cuff

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2009/042539 Ceased WO2009135138A1 (en) 2008-05-02 2009-05-01 Self expanding electrode cuff

Country Status (7)

Country Link
US (3) US20110160827A1 (enExample)
EP (2) EP2310084B1 (enExample)
JP (2) JP5575113B2 (enExample)
CN (2) CN102112177A (enExample)
AU (2) AU2009242504A1 (enExample)
CA (2) CA2722987A1 (enExample)
WO (2) WO2009135142A1 (enExample)

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US8983572B2 (en) 2010-10-29 2015-03-17 Inspire Medical Systems, Inc. System and method for patient selection in treating sleep disordered breathing
US9227053B2 (en) 2008-05-02 2016-01-05 Medtronic, Inc. Self expanding electrode cuff
US9486628B2 (en) 2009-03-31 2016-11-08 Inspire Medical Systems, Inc. Percutaneous access for systems and methods of treating sleep apnea
US9889299B2 (en) 2008-10-01 2018-02-13 Inspire Medical Systems, Inc. Transvenous method of treating sleep apnea
US9888864B2 (en) 2010-03-12 2018-02-13 Inspire Medical Systems, Inc. Method and system for identifying a location for nerve stimulation
US10932682B2 (en) 2008-05-15 2021-03-02 Inspire Medical Systems, Inc. Method and apparatus for sensing respiratory pressure in an implantable stimulation system
US11298540B2 (en) 2017-08-11 2022-04-12 Inspire Medical Systems, Inc. Cuff electrode

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EP2310082A1 (en) 2011-04-20
US9227053B2 (en) 2016-01-05
WO2009135138A1 (en) 2009-11-05
JP5575113B2 (ja) 2014-08-20
AU2009242504A1 (en) 2009-11-05
CN102112177A (zh) 2011-06-29
EP2310084A1 (en) 2011-04-20
CN102202726A (zh) 2011-09-28
CA2722987A1 (en) 2009-11-05
US20110160827A1 (en) 2011-06-30
EP2310082B1 (en) 2015-10-21
EP2310084B1 (en) 2016-03-23
JP5538367B2 (ja) 2014-07-02
JP2011519627A (ja) 2011-07-14
US20110147046A1 (en) 2011-06-23
AU2009242500A1 (en) 2009-11-05
JP2011519630A (ja) 2011-07-14
CA2722982A1 (en) 2009-11-05
US20160184581A1 (en) 2016-06-30

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