Confidential
`
`MEMORANDUM
`
`To:
`
`John Pafford .
`David Brumfield
`
`From:
`
`Larry Boyd
`
`Date:
`
`January 11, 1994
`
`cc: Ted Bird
`Ron· Pickard
`Alex Lukianov
`Rick Duer
`v"Brad Estes
`Roger White
`
`Subject: MEETING WITH DR. GARY KARLIN MICHELSON
`
`On Tuesday, January 11, Ron Pickard, Rick Duerr, Mark Merrill, and I met with Dr.
`Michelson and his attorneys. While the attorneys worked out the details of the various
`agreements, Ron Pickard and I were able to meet with Dr. Michelson to review his various
`ideas on interbody fusion and spinal surgery. Dr. Michelson reviewed with us the many
`assorted prototype implants and 4lstruments covering a wide range of subjects.
`
`Initially, Dr. Michelson pointed out that there are generally three steps performed in a
`spinal surgery. These would be a discectomy, an interbody fusion via either posterior or
`anterior approach, and some form of instrumentation for additional stability. Dr.
`Michelson pointed out that the ideal case would be to eliminate the need for additional
`instrumentation via improving the biomechanical performance of the implant used for.
`interbody fusion. This would appear to be the ultimate goal of the various implant and
`instrumentation systems for interbody fusion that we were to'discus with Dr. Michelson..
`
`Next, Dr. Michelson reviewed step-by-step some oI the details of the surgical procedure for
`posterior interbody fusion approach:
`
`1.) The fust step involved detailed pre-operative planning. This would be via templates of·
`the various implant sizes that would be available in various magnification ranges. A
`lateral X-ray would be used to .pre-operatively assess the anticipated implant depth and
`allow the surgeon to assess the anticipated implant height required in order to restore
`normal anatomy. An axial CT scan would be used to clarify the actual disc space available
`and the true anticipated implant depth to be used.
`
`I...ub~~·
`~HIBIT NO.J;;..:~:II
`"/4.lt c>
`J. HOSTETLER
`
`Conlldentla' Inlannttlon
`
`MSD 1041411
`
`PX0114-0001
`
`PX0114
`
`WARSAW2005
`NuVasive, Inc. v. Warsaw Orthopedic, Inc.
`Case IPR2013-00206
`
`Page 1
`
`

`
`Meeting with Dr. Gary Michelson
`January 11, 1994
`Page 2
`
`2.) The second step would involve removing some small portion of disc after an exposure
`of the disc froIn a posterior approach. A simple curette 01' rongeur could be used to
`remove enough disc to allow for placement of the initial bullet-nosec;i long distractors.
`
`3.) The third portion of the procedure involves placement incrementally of various bullet(cid:173)
`nose long distractors. These will indicate to the surgeon when the normal disc height has
`been restored. The surgeon will be able to feel as the disc space becomes inaeasingly taut
`and stable. The long distractors also assure that a central axis parallel to the endplates is
`achieved prior to any drilling. Dr. Michelson pointed out that this predistraction phase is
`It is important that the patient be fused in the fully extended, distracted
`very critical.
`position, as opposed to some surgeons who have accidentally fused patients in a collapsed
`p·osition resulting in eventual degeneration of adJacent disc levels. This predistraction is
`critical also to giving the necessary working space for insertion of the instrumentation and
`implant.
`.
`
`4.) The next phase involves impacting into the vertebral body an external
`tubular
`distractor (with engagement teeth) which will be the working channel for the rest of the
`procedure. This helps to maintain distraction throughout the procedure, along with the
`contralateral distractor. At this pomt, Dr. Michelson pointed out that it will be necessary to
`lock the surgeon into a given depth and diameter instrumentation set. Dr. Michelson
`suggested that the various depths used be color coded and that the surgeon be locked into
`using a given set for a predetermined diameter, also. At this point, the surgeon would
`then work with a specific set of reaming and tapping instrumentation, in order to avoid
`for mixing of different sized i!:lstrumentation.
`any potential
`
`5.) The next phase is the insertion of the diameter-reducing inner sleeve and the protected
`drilling of the disc and bone in preparation for the implant. Having set the stage in terms
`of the surgical procedure, Dr. Michelson discuSsed some of the more specific details of the
`design. He mentioned that cutting an arc is a means of increasing the surface area contact
`and therefore reducing the likelihood of subsidence. He mentioned some data and
`analysis via computer modeling that was performed that clearly shows the advantage of
`both the domed shape. as· well as a tooth thread engagement into the vertebral bodies as
`opposed to simply placing a flat member in contact with the vertebral bodies. We will
`need to examine this information, now that the agreement is in place.
`
`Dr. MiChelson also mentioned that the device used to remove the disc and bone is riot a
`typical sharp-pointed drill, but a side-cutting reamer that actually draws the disc and bony
`debris .into the internal diameter-reducing sleeve. This captures the debris which would
`otherwise migrate about the body and perhaps cause further inflammation.
`
`CDntldential InlDmation
`
`MaD 1041472
`
`PX0114-0002
`
`Page 2
`
`

`
`Meeting with Dr. Gary Michelson
`.
`January 11, 1994
`Page 3
`
`6.) The next step is to remove a dowel of iliac crest autograft bone and load the implant
`with bone via the implant bone loading device, followed by insertion of the implant. This
`device holds the implant and bone dowel and drives the bone into the device. The bone is
`compacted into the device and extrudes from the pores in the device. Bone tapping. is not
`normally required due to the fact that the implant is self tapping. Tapping could in fact
`result in potential cross threading and a less than ideal fit between the implant and bony
`interface. We will need to do some studies of our own to assess the need for tapping in the
`. various cervical, thoracic, and lumbar applications of the implant and instrwnentation.
`
`We then discussed some of the specific implant features. The implant holes were
`contrasted with the two large holes on the Spine Tech BAK system. The width to depth
`ratio has a clear affect on bone ingrowth and incorporation through the implant. Dr.
`Michelson mentioned some studies that exist showing that the' width aaoss a hole must
`be at least as great as the depth, or thickness, of the material through which the bone must
`bridge. However, he pointed out that beyond some certain ratio if the bone width is too
`great incorporation will be less than ideal, as will load bearing capacity. This apparently
`has to do with the amount of support vs. thrugrowth of bony trabeculae provided by the
`I asked Dr. Michelson about the reasons for the small holes along the side of the
`implant.
`implant. This is contrasted with some other devices (BAK, Ray) which have left the sides
`of the implant closed in order to, supposedly, prevent fibrous tissue migration into the
`device, Dr. Michelson pointed out that this was a very clear misunderstanding on some
`investigators part. He stated that, in actuality, the way that he has judged success of a
`fusion has been by noting bony bridging along the outside of the implant. As such, he feels
`that the side holes and the bone that extrudes through them act as an aid in allOWing the
`bone to grow not only through the implant but actually around and encasing the implant.
`
`Dr. Michelson also mentioned. that the HA coating is a preferred embodiment for the
`implant design, as this will further encourage active bone bonding and the migration of
`bone along the implant. He discussed the need to look into both short-tenn mcalcium
`phosphate and longer term hydroxyapatite coatings. The FDA's thoughts on a short-term
`vs. a long-term coating may weigh into this decision. Finally, he pointed out the good
`histology shown in animal studies that has demonstrated complete encasement of
`threaded implants in bone with bone bridging both through and arotUld the implant.
`
`I was
`Dr. Michelson reviewed all the implants and instruments already manufactured.
`most impressed with the manufacturing work done on all these components. Please see
`the attached copies of photographs given to me showing the complete instrumentation set
`for the posterior lumbar .interbody fusion technique. Some additional instruments are
`required for the anterior lumber interbody fusion. We will be in touch with Dr. Michelson
`with the completion of the final agreement to secure several full sets of implants and
`instruments for review with other surgeons and for further design and development of
`this concept.
`
`CDnfldBntll11ntormltion
`
`MSD1041473
`
`PX0114-0003
`
`Page 3
`
`

`
`Meeting with Dr. Gary Michelson
`January 11,1994
`Page 4
`
`Next, Dr. Michelson discussed application of his device for an anterior lumbar interbody
`fusion. He pointed out that during an anterior lumbar iriterbody fusion it is necessary to
`clearly visualize the posterior wall. in order to remove any extruded disc fragments and
`make sure that all extruded or herniated disc fragments have been retrieved.
`It was not
`extremely clear what method was preferred for disc evacuation. Dr. Michelson implied
`that the method used for the discectomy would be a typical rectangular incision in the
`annulus followed by a use of curette and rongeurs tor evacuation of the disc and exposure
`of the vertebral endplates. However, I was somewhat concerned about the lack of any
`ligament or medial
`central restraining structures such as the anterior longitudinal
`portions of the nucleus to prevent contact between the two. bilateral devices. This is a
`subject that I will hope to cover with Dr. Michelson and other surgeons using threaded
`dowel techniques via an anterior approach. It appears that contact between the devices is
`not a concern.
`
`Dr. Michelson pointed out a very interesting concept for attaching a threaded dowel to the
`vertebral.bodies via placement of an external staple. A figure of this is shown below.
`
`c
`
`'4
`.~'O
`
`This takes advantage of the fact that the threaded cage has a 1 degree of freedom method of
`extrusion, that is, via rotational unscrewing; The staple would have a 1 degree of freedom
`method of extruding via axial pull~out. When one combines these two fixation methods
`they act in concert to seemingly reduce the potential dislocation of the other. Additionally,
`the staples are placed such that they are driven into holes which over estimate their
`angulation and therefore compress down on the implant as they are driven into the
`vertebral bodies. A lock screw fixes the staple to the implant. The staples are low profile
`
`confldentlll h\latmlUan
`
`MSD 1041474
`
`PX0114-0004
`
`Page 4
`
`

`
`Meeting with Dr. Gary Michelson
`January 11, 1994
`PageS
`
`against the vertebral bodies. The round vertebral body is flattened via rongeurs or burrs to
`further encourage conformation of the staples to the vertebral body.
`.
`
`The methodology of distraction followed by compression is something most surgeons
`would be very familiar with. Testing would certainly be needed on the concept. However,
`this sort of technique of anchoring and attaching an interbody fusion device with some
`sort of an external member for purchase of the vertebral bodies has been contemplated as
`part of the IBFD project with Dr. Kozak, also. Staples are clearly clinically well·known
`devices and likely to be well accepted in this sort of spinal surgery. This technology is not
`covered by the current agreement but. could be added later if there is such an interest. Dr.
`Michelson reinforced the· fact that the current device alone is and has been found to be
`very safe without the use of the staples. Therefore, the staples may very well not be
`required in order to achieve a very good and successful result with the threaded dowel in
`an anterior lumbar interbody fusion. We will likely further review this concept later as we
`move forward with the development of this device.
`
`Next, we discussed the difference between Dr. Michelson's concept and that of the BAr<
`implant from Spine Tech. Overall, Dr. Michelson emphasized the fact that the primary
`design philosophy is to gently remove bone so as to not harm· in any way the surrounding
`biological structures. Another goal is to maximize the available surface area for load
`bearing in order to reduce the likelihood of implant subsidence. Dr. Michelson discussed
`the Spin~ Tech device, emphasizing the limited area available for bone placement. The
`.Spine Tech device provides for only a minimal amount of bone autograft placement. The
`polyethylene endcaps, increased sidewall thickness, Acm~type (square) threads, and the
`central strut all take up a great deal of room that is not available for bone. The Spine Tech
`device cannot be preloaded due to the central strut, which is used for strength and for
`driving the implant. The central internal strut has a slot used for engagement and
`insertion of the implant. However, this presents difficulty when one attempts to unthread
`or remove the implant due· to lack of a positive locking onto the implant. This is
`contrasted with the very positive threaded and keyway attachment used with Dr.
`Michelson's technique, as documented in the patent drawings.
`
`The Spine Tech BAK implant provides for a gradual tapered bullet·nosed lead in area to
`distract the disc space as inserted, where Dr. Michelson's technique achieves distraction via
`external means, presenting some very clear biomechanical and sUrgical advantages.
`
`The Spine Tech device provides for no side holes due to their concerns over disc and
`fibrous tissue end growth. However, Dr. Michelson feels very strongly about
`the
`likelihood of bone bridging and incorporation not only through the implant, but along .the
`outer margins.
`
`Confldent\allnformltlon
`
`MSD 1041475
`
`PX0114-0005
`
`Page 5
`
`

`
`Meeting with Dr. Gary Michelson
`January 11, 1994
`Page 6
`
`Spine Tech's square Aane thread creates potential stress risers. and sets up the potential for
`fracturing and damage to the endplates, where the very fme V-thread of Michelson
`provides for a very strong engagement, yet an a traumatic cutting of the vertebral bone.
`
`The Spine Tech device features polyethylene endcaps thought needed for visualization.
`However, it was found that visualization was still not possible for fusion confirmation
`the true ~ign of a
`even with the polyethylene endcaps. As mentioned previously,
`successful fusion has been bridging bone all around the implant between the vertebral
`bodies as a sign of a good surgical result.
`..
`
`Dr. Michelson mentioned some concerns expressed by Dr. Marie-H~lme Plais about
`method~ lor achieving lordosis with the implant. Dr. Michelson discussed the use of
`various wedge-shaped bullet distractors. The AUF and PLIF distractors provide for a
`trapezoidal..shape distraction, as shown below:
`
`.'
`
`ALIF
`
`t'LrF
`These would then be followed by a trephine method to cut along these wedge-shaped
`trapezoidal endplates. That is, the long distractors must be left in place in the trephine
`method in order to maintain the lordosis.
`
`We then discussed some additional aspects of the use of the short distractors. These short
`distractors are used for balancing the bilateral placement of the devices. These are .the last
`step in the incremental sizing process and may be especially important when reducing a
`spondylolisthesis. Dr. Michelson pointed out that a spondylo1isthes~ is generally reduced
`by vertical·re-establishment of disc space height, rather than trying to horizontally pull the
`vertebral body back. That is, due to the tensile nature of the surrounding. annulus the
`establishment of disc height tends to swing the vertebral body up and back in a 4-bar
`mechanism-type motion.
`.
`
`confldlnUlllnfonnltlon
`
`MSD 1041476·
`
`PX0114-0006
`
`Page 6
`
`

`
`Meeting with Dr. Gary Michelson
`January 11, 1994
`Page 7
`
`Dr. Michelson also pointed out that the external tube used after the long distractors are
`placed is actually important in keeping the vertebral bodies from splaying apart during the
`various drilling techniques. He pointed out that with a Spine Tech or Ray device the use
`of drills (as opposed to reamers) and the lack of the use of an external fixed tube means that
`as the drill engages one side of the vertebral body it is very likely to splay off to one side
`avoiding contact with the other and drill out a non-uniform, non-parallel drill hole for
`placement of the impl.ant.
`
`We next discussed some other non-threaded concepts that Dr. Michelson has developed
`over the years. Dr. Michelson mentioned that as early as 1985 he manufactured some solid
`and hollow rectangular blocks for PLIP. These blocks featured teeth to resist expulsion and
`may in fact pre-date the work of Brantigan. These were developed because of his concerns
`about·the lack of good bone for use in PLIF procedures. Dr. Michelson also discussed some
`alternative non-threaded circular dowel concepts. These involve use of either a knurled
`structure or a tooth structure that would allow the devices to be pounded in vs. threaded.
`While certainly not preferred over the threaded technique, these concepts filed as design
`patents, may prevent others from using these to circumvent the Michelson threaded
`dowel patents. Dr. Michelson also reviewed with us design patents covering all the
`various hole and slot configurations for the implant, which further protect the concept
`from competitive copying. These designs are all part of the agreement with Dr. Michelson.
`
`Dr. Mich~lson also showed us an expanding block method of placing an interbody implant
`and expanding it in vivo. This involves driving wedges together in order to achieve an
`increase in height, much as had been pursued in some of the early work with the Kozak
`IBFD program. He also showed how the expanding blocks could be used to expand a
`cylinder and such technology may be of interest especially for percutaneous placement of
`I will further review these concepts with Brad Estes and· see
`an interbody fusion device.
`how they may factor into the percutaneous IBFD project, currently in the research phase.
`This design is part of the purchase agreement with Dr. Michelson.
`
`Dr. Michelson also showed us some truncated cylinders. These truncated cylinders are
`necessary in areas of the ·lumbar spine where the height to width ratio begins to favor a
`taller disc with a smaller width available. This would present problems in attempting to .
`place circular dowels bilaterally while avoiding contact between the dowels. In such cases,
`it may be necessary to use truncated c.ylinders where the circular portions engage the
`vertebral bodies while there are flat vertical portions between the implants to avoid
`contact. These designs would be push-in designs. These designs are part of the ·purchase
`agreement with Dr. Michelson.
`
`Overall, we will need to make sure that patent applications are filed on all these concepts,
`some of which we will want to pursue later and others which are defensive patents.
`
`conndenuallnformlltlon
`
`MSD 1041417
`
`PX0114-0007
`
`Page 7
`
`

`
`Meeting with Dr. Gary Michelson
`January 11, 1994
`Page 8
`
`Dr. Michelson then showed us an interesting application of the threaded dowel concept in
`a non-spine application. He had a sample of a foot model that used two bilateral threaded
`dowels in an ankle fusion. Dr. Michelson expressed a great deal of enthusiasm for this
`device and stated that an orthopaedic foot specialist that·he talked with was interested in
`evaluating the device. He also mentioned the potential for using the threaded dowel
`technique for fusing other joints in the small joint arena, such as the. elbow or the first
`metatarsophalangeal joint (or great toe).
`In the great toe application, we discussed the
`possibility of using the threaded dowel to aoss the joint space and achieve fusion while
`using the staple flXation method discussed above to then lock the implant into a certain
`position for fusion. The appeal of all of these non-spine applications could be. the potential
`for a 510Ck) application by their similarity to other implants already used for a fusion across
`a joint space, such as an interference screw technique used in other areas.
`I will further
`look into both the market size and applicability to various non-spine procedures for this
`threaded dowel technique.
`I will also look at existing implants small joint fixation means
`and the potential for SlO(k) application of the threaded dowel technique related to these
`techniques.
`
`We discussed .the potential for a retroperitoneal lateral approach to the spine. As you may
`know, a retroperitoneal approach (as opposed to a transperitoneal approach) is used by
`many spine surgeons for anterior surgery especially at the L5-S1level. The retroperitoneal
`approach to the lateral spine at L4~5 and L3-4 would avoid the need for manipulation of
`the blood vessels, provide for greater depth across the larger transverse dimension, allow
`for an increased surface area contact due to this greater transverse'depth and result in less
`danger of neurovascular damage due to protrusion into the relatively benign psoas muscle
`on the opposite lateral side of the procedure. Dr. Michelson reviewed with us some
`excellent instrumentation developed for placement of the threaded dowel via an lateral
`anterior approach. All the instrumentation was very similar to that already developed,
`simply enlarged and slightly modified for an anterior approach. A large, bullet-nosed
`distractor is placed and an X-ray is used to confirm that the lateral position is parallel to the
`correct plane. An outer multiple-wedge cannula is driven into the disc space to provide
`for lordosis.
`
`These wedges also then provide protection during procedure by acting as shields of the.
`anterior vessels and the posterior spinal canal. The inner, bullet-nosed distractor is
`removed, reamers placed and the implant is threaded in as before. I·discussed the fact that
`such an implant may actually be more biomechanically sound due to the potential for
`greater load bearing along the stronger peripheral bone. However, the biomechanical
`performance of a single implant located centrally, especially in terms of flexion extension
`motion, would need to be further explored via mechanical cadaveric testing.
`
`Confldentlll Infonnltlon
`
`MSD 1041478
`
`PX0114-0008
`
`Page 8
`
`

`
`Meeting with Dr. Gary Michelson
`January 11, 1994
`Page 9
`
`Dr. Michelson then reviewed the various non-threaded concepts developed for use in
`cervical spine fusions. He showed us the current standard - the allograft fibula slice (used
`much as the femoral allograft is used in the lumbar spine).
`It was very clear that the
`allograft fibula has a relatively small surface area available for contact and due to .being
`quite smooth may be prone to anterior expulsion. The fusion device implants designed.
`for this application feature teeth and holes to prevent expulsion and allow bone ingrowth..
`The implant is packed full of bone and a slide-in plate along the front is placed to
`completely seal the implant. The various staple methods discussed .for the lumbar spine
`could be used in the cervical spine to further anchor the implant.
`
`The preferred use of the .implant would be as an isolated disc fusion without the use of an
`anterior cervical plate. However, such anterior cervical plates could be used in revisions
`or in extreme cases. A prospective study could be performed rather easily comparing this
`implant with the allograft fibular slices currently used. Dr. Michelson pointed out that
`revision of this implant for a pseudoarthrosis could be easily performed via some
`additional posterior instrumentation to provide additional stability. That is, the surgeon
`could simply provide additional stability (via added instrumentation) in the case of a
`pseudoarthrosis which would likely result in fusion and restoration of stability. This is in
`contrast to the use of the allograft fibula slice, where failure normally results in subsidence
`of the disc space and the requirement that a revision operation proceed anteriorly, initially
`to restore disc height. Such an anterior revision of a fibular graft may well involve some
`fairly radical procedures to revise.
`'.
`Dr. Michelson mentioned that the size range would most likely be disc heights of 6, 7, 8,9
`mm,disc depths of 11, 14, and 17 mm and perhaps two widths depending on the amount
`of variation we would want to allow for. Overall, the instrumentation is developed, the
`implants basically developed, and seem sound though biomechanical testing would be
`required. This technology was induded in the purchase agreement with Dr. Michelson.
`
`Dr. Michelson then reviewed with us his spinal irrigator concept, his spinal marker needle
`design, his rongeur concepts, and some electrical stimulation concepts. All these concepts
`appear very well thought out and have direct application to spine. The irrigator, marker
`needle, and rongeur concepts are covered by Michelson patents (not part of the current .
`agreement with Dr. Michelson), The irrigator concept provides for easy removal of
`particulate debris in discectomies and provides for containment of disc debris fragments
`during irrigation. The marker needle provides for easy confirmation of spinal level and
`marking of surgical location prior to disc surgery, once confmned via lateral x~ray. The
`rongeurs are extremely sound, biomechanical designs that allow for very easy and rapid
`removal of bone. They would have a disposable insert that would allow for loading with
`the removed bone prior to disposal. The rongeurs could also be developed in· an
`automated electrical version using a solenoid-driven guillotine that would apply a pre~set·
`and safe cutting force.
`
`Confldtnll811nlormatlon
`
`MSD 1041419
`
`PX0114-0009
`
`Page 9
`
`

`
`Meeting with Dr. Gary Michelson
`J~nuary 11, 1994
`. Page 10
`
`I was
`Overall, I found the time spent with Dr. Michelson to be extremely worthwhile.
`quite impressed with breadth and depth of the work performed by Dr. Michelson. The
`instrumentation was extremely well thought out and very well made. I will be working to
`further clarify my understanding of the various implants and instruments.
`I will look
`into securing sets of implants and instruments for review with surgeons and as a starting
`point for development of our own instrumentation set.
`It is clear that discussions will
`take place to further plot out the strategy and project planning for moving forward with
`these technologies.
`I will look forward to meeting with you as we further solidify the
`development of a threaded bone dowel and non-threaded concepts based on those
`discussed in these minutes.
`In the meantime, please do not hesitate to call me with any
`questions, comments, or concerns regarding any of the discussed subjects.
`
`LB/dg
`
`Confldant\.' \nfolmltlon
`
`·MSD :1041480
`
`PX0114-0010
`
`Page 10
`
`

`
`CantldenltallnformaUon
`
`MSD 1041481
`
`PX0114-0011
`
`Page 11