`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`Baxter Healthcare Corp., ApaTech, Inc., and ApaTech Limited,
`Petitioners
`
`v.
`
`Millenium Biologix, LLC,
`Patent Owner
`
`Patent No. RE41,251
`Issued: April 20, 2010
`Filed: January 30, 2008
`Inventors: Sydney M. Pugh, Timothy J. N. Smith,
`Michael Sayer, and Sarah D. Langstaff
`Title: SYNTHETIC BIOMATERIAL COMPOUND OF CALCIUM
`PHOSPHATE PHASES PARTICULARLY ADAPTED FOR SUPPORTING
`BONE CELL ACTIVITY
`
`Patent No. 6,585,992
`Issued: July 1, 2003
`Filed: October 4, 2001
`Inventors: Sydney M. Pugh, Timothy J. N. Smith,
`Michael Sayer, and Sarah Dorthea Langstaff
`Title: SYNTHETIC BIOMATERIAL COMPOUND OF CALCIUM
`PHOSPHATE PHASES PARTICULARLY ADAPTED FOR SUPPORTING
`BONE CELL ACTIVITY
`____________________
`
`Inter Partes Review Nos. IPR2013-00582 and IPR2013-00590
`
`Before SCOTT E. KAMHOLZ, MICHELLE R. OSINSKI, and BRIAN P.
`MURPHY, Administrative Patent Judges
`__________________________________________________________________
`Declaration of Professor Andrew J. Ruys
`
`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 1
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 2
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`
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`TABLE OF CONTENTS
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`
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`I.
`
`INTRODUCTION ........................................................................................... 1
`
`A.
`
`B.
`
`C.
`
`Engagement And Summary .................................................................. 1
`
`Background And Qualifications ............................................................ 1
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`Compensation And Prior Testimony ..................................................... 2
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`II.
`
`EXPERIMENTAL SUMMARY ..................................................................... 2
`
`A.
`
`B.
`
`Preparation of Materials Pursuant to Ruys 1993a ................................. 2
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`Analysis of Materials ............................................................................ 5
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`1.
`
`2.
`
`3.
`
`4.
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`Scanning Electron Microscopy ("SEM") .................................... 5
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`Hydrostatic Weighing ............................................................... 15
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`Nano-CT .................................................................................... 17
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`Summary ................................................................................... 18
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`APPENDIX A .......................................................................................................... 19
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`
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`iii
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 3
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`
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`TABLE OF APPENDICES
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`List of Materials Considered
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`
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`Appendix A:
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`iv
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 4
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`
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`I.
`
`INTRODUCTION
`
`A. Engagement And Summary
`1.
`
`I was retained by counsel for Baxter Healthcare Corp., ApaTech, Inc.,
`
`and ApaTech Limited and asked to replicate the experiments described in "A
`
`Feasibility Study of Silicon Doping of Hydroxylapatite," Interceram, Vol. 42, No.
`
`6, 372-74 (1993) ("Ruys 1993a") (Ex. 1011), a publication on which I am the only
`
`named author.
`
`2.
`
`Based on my experiments and subsequent analysis, I have determined
`
`that the silicon-substituted calcium phosphate materials I prepared using the
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`methodology I disclosed in Ruys 1993a exhibit a microporous structure.1 In
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`addition, the materials I prepared and analyzed exhibit a morphology characterized
`
`by interconnected pores throughout the material.
`
`B.
`3.
`
`Background And Qualifications
`
`I am currently the Director of Biomedical Engineering (Education),
`
`School of Aerospace Mechanical & Mechatronic Engineering, at The University of
`
`Sydney in Sydney, Australia.
`
`
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`1 I was the Chief Scientist on these tasks. As is typical in a research setting,
`
`however, some of the experiments and analysis were performed by qualified
`
`scientists working under my close supervision.
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`1
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 5
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`
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`
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`4.
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`I received my Bachelors in Engineering (Honours 1) in 1987 and my
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`Ph.D. in 1992 from the University of New South Wales in Kensington, Australia.
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`5.
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`A complete list of my publications and a description of my other
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`credentials and accomplishments are provided in my curriculum vitae, which is
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`attached as Exhibit 1143.
`
`C. Compensation And Prior Testimony
`6.
`
`I am being compensated at a rate of $500 per hour for time spent in
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`connection with services rendered during the pendency of this matter. I am also
`
`being reimbursed for reasonable and customary expenses associated with my work
`
`in this proceeding.
`
`7.
`
`I have not previously testified in Federal District Court or in any other
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`legal proceedings.
`
`II.
`
`EXPERIMENTAL SUMMARY
`
`A.
`8.
`
`Preparation of Materials Pursuant to Ruys 1993a
`
`I was asked by counsel to replicate the experiments described in my
`
`publication entitled "A Feasibility Study of Silicon Doping of Hydroxylapatite,"
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`Interceram, 42(6) 372-374 (1993) ("Ruys 1993a") (Ex. 1011). In so doing, I used
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`only those techniques and methods that would have been available in 1993.
`
`9.
`
`I have attached a copy of my laboratory notebook as Exhibit 1144 to
`
`this declaration. The first three pages of my laboratory notebook (excluding the
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`2
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 6
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`
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`cover page) contain the experimental protocol I used to prepare eight samples of
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`silicon-substituted calcium phosphate materials. The experimental protocol in
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`Exhibit 1144 is the same process that is described in Ruys 1993a.
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`10.
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`In the method described in Ruys 1993a, I had prepared a total of
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`eleven (11) experimental compositions with Si:HAP molar ratios of 0.09, 0.18,
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`0.36, 0.75, 1.65, 1.68, 2.29, 6.94, 11.97, 24.31, and 50.38, as well as a silicon-free
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`control sample.
`
`11. As I describe in the paper, the purpose of the study was "the
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`development of a silicon-doping procedure and the quantification of the effects of
`
`silicon on the structure and properties of HAP, in order to establish the suitability
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`of silicon-doped HAP for clinical trials." Ex. 1011 (Ruys 1993a) at 3.
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`12. Not all the samples made would be considered relevant by a person of
`
`ordinary skill in the art. From a compositional standpoint, the paper notes the
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`formation of a "glassy phase" of an Si-P-O glass (which is not a hydroxyapatite) at
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`"high addition levels," and in particular, levels greater than Si:HAP of 1.65. Id. at
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`4. The paper concentrated on Si:HAP ratios at or below the saturation level of Si
`
`(achieved at an Si:HAP ratio of 1.65), and as described in the paper, I did not
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`report measured results for (nor was I able to measure in some cases) any samples
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`with Si:HAP levels over 6.94. Id at 4 and Figs 1-3.
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`3
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 7
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`
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`13. Given these considerations and the time and resource constraints of
`
`this project, I chose to prepare a subset of the experimental compositions I had
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`previously prepared and described in the Ruys 1993a paper; namely, those with
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`Si:HAP molar ratios of 0.09, 0.18, 0.36, 0.75, 1.65, 1.68, 2.29 and a silicon-free
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`control sample. I did not prepare compositions corresponding to the other four
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`Si:HAP molar ratios reported in Ruys 1993a (i.e., those with Si:HAP molar rations
`
`of 6.94, 11.97, 24.31, and 50.38). I labeled the eight (8) experimental
`
`compositions I prepared according to the following table:
`
`Sample
`H1
`H2
`H3
`H4
`H5
`H6
`H7
`H8
`
`Si:HAP molar ratio
`Control
`0.09
`0.18
`0.36
`0.75
`1.65
`1.68
`2.29
`
`
`
`14. My laboratory notebook in Exhibit 1144 also contains a detailed
`
`record of the experiments conducted and my observations.
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`4
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 8
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`
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`15. After preparing the materials according to the protocol in Exhibit
`
`1144, I took a photograph of the eight (8) samples I prepared, labeled H1-H8,
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`which I have attached as Exhibit 1145.
`
`B. Analysis of Materials
`16.
`
`I used standard analytical techniques to further analyze the materials I
`
`prepared. Specifically, I analyzed the materials using: (1) Scanning Electron
`
`Microscopy ("SEM"); (2) Hydrostatic Weighing; and (3) Nano-Computed X-Ray
`
`Tomography ("Nano-CT").
`
`1.
`
`Scanning Electron Microscopy ("SEM")
`
`17. To prepare the samples for scanning electron microscopy ("SEM"), I
`
`coated them with 25 nm carbon-sputter coating. Sputter coating covers a sample
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`with a thin layer of conducting material, which enables the sample to be viewed on
`
`a scanning electron microscope. A 25 nm carbon coating is a standard surface
`
`coating for ceramics.
`
`18.
`
`I conducted SEM on a Zeiss EVO 50 scanning electron microscope
`
`using magnifications up to nearly 6000 times to view and image samples H1 to H6.
`
`Due to constraints on instrument availability, I was not able to view and image
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`5
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 9
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`
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`samples H7 and H8. I have attached images of samples H1 to H6 as Exhibits
`
`1146-1158 to this declaration.2
`
`19. The scanning electron microscope I used to image the samples utilizes
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`AZtecEnergy EDS ("Energy Dispersive Spectroscopy") analysis software. The
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`software allows one to perform a detailed analysis of an SEM image. I used one
`
`feature of the software in my analysis, which was the software's built-in
`
`measurement tool. The measurement tool measures the distance between two
`
`selected points in an SEM image.
`
`20.
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`I used the instrument's measurement tool to measure the diameter of a
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`pore in sample H4, which has a Si:HAP ratio in the middle of the range of samples
`
`that were prepared.3 Exhibit 1153 shows an SEM image of sample H4, which
`
`
`2 Exhibits 1146-1148 are SEM images of sample H1, Exhibits 1149-1150 are SEM
`
`images of sample H2, Exhibits 1151-1152 are SEM images of sample H3, Exhibits
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`1153-1154 are SEM images of sample H4, Exhibits 1155-1156 are SEM images of
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`sample H5, and Exhibits 1157-1158 are SEM images of sample H6.
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`3 I chose sample H4 because the size of the pores in this sample appear to be
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`consistent with the size of the pores of the other samples. Thus, this sample
`
`appears to be a fair representation of all the samples. As to the particular pore
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`measured, I chose this pore at random.
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`6
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 10
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`
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`includes this measurement. The line connecting the two "X" marks is applied
`
`using the measurement tool of the instrument. The software automatically
`
`calculates the length of the line connecting the two "X" marks. In this example in
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`Exhibit 1153, the measurement tool indicated that the measured pore has an
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`approximate diameter of 659 nm.
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`21. Once I finished imaging the samples on the scanning electron
`
`microscope, I visually inspected the resulting images. Collectively, the images of
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`the silicon-substituted samples (H2-H6 in Exhibits 1149-1158) show that the
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`materials exhibited a substantially uniform pore size across all the samples.
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`22.
`
`I was able to determine by visual inspection of the samples that I
`
`prepared that all of the silicon-substituted calcium phosphate materials exhibit a
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`morphology of interconnected particles. This can be seen by simply looking at the
`
`images. The pores that are visible in the material are created by interconnected
`
`particles. Specifically, the images show that the outer boundary of many of the
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`pores are established by multiple calcium phosphate particles that have not
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`completely fused together.
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`23. The images of the pores also show that they are interconnected. The
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`images show that the sample exhibits a granular surface morphology (as seen by
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`the projections, pits, and shadows) and the images provide a clear sense of depth
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`7
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 11
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`
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`that can be seen on the sample surface. This morphology is found throughout the
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`sample and is indicative of interconnected voids, i.e., pores.
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`24.
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`I chose to examine one image of sample H4 in further detail. I chose
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`the image in Exhibit 1153 since I had already measured one pore in the image
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`using the scanning electron microscope.
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`25. Each of the SEM images, including Exhibit 1153, contains a legend
`
`with a micron bar (i.e., a scale) at the bottom left of the image, which represents
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`the relationship between a measurement on the image itself and the corresponding
`
`measurement on the physical sample. In Exhibit 1153, the length of the micron bar
`
`corresponds to an actual measure of 2 micrometers ("µm") on the sample. Using
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`this information, the diameter of a pore can be measured on the image and
`
`converted into an approximate measure of the actual diameter of the pore in the
`
`sample.
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`26.
`
`I measured the diameter of each pore in the upper right quadrant of
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`the image in Exhibit 1153 using a ruler. There were 90 pores in this quadrant of
`
`the image. I chose the upper right quadrant randomly. As can be seen in the
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`image, the pores are elliptically shaped. Due to the elliptical, non-spherical shape
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`of the pores, I chose to measure both the height and width of each pore for greater
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`accuracy. After I measured each pore, I drew a red dot in the pore. I have attached
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`a version of the image containing my annotations as Exhibit 1159. Two pores
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`8
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 12
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`
`
`
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`(circled) were not measured because they were not fully visible on the image. The
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`raw measurements are contained in my laboratory notebook, which is attached as
`
`Exhibit 1144.
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`27. Using the micron bar scale, I then converted the raw measurements to
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`the corresponding measures of the actual heights and widths of the pores in the
`
`sample. From these values I calculated the average elliptical aspect ratio for the
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`pores (which is the proportional relationship between the average pore width and
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`the average pore height). I then prepared a pore size distribution curve for the
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`pores (attached as Exhibit 1160 and reproduced below), which followed a normal
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`distribution, from which I calculated: (1) the mean of the pore-width normal
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`distribution curve; (2) the mean of the pore-height normal distribution curve; (3)
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`the mean of the pore-diameter normal distribution curve on an equivalent circular
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`pore basis; (4) the width range; and (5) the height range. The calculations and
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`analysis I used to arrive at these values appears in my laboratory notebook attached
`
`as Exhibit 1144.
`
`28. Based on my calculations and analysis, I have determined that sample
`
`H4 has the following pore dimensions:
`
`•
`
`•
`
`Average Elliptical Aspect Ratio: 1.845:1
`
`Mean Pore Width: 455 nm
`
`•
`Mean Pore Height: 255 nm
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`9
`
`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 13
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`
`
`
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`• Width Range: 65-715 nm
`
`•
`
`Height Range: 35-385 nm
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`29. The pore size distribution curve, attached as Exhibit 1160 and
`
`reproduced below, plots approximate pore height/width measurements on the X
`
`axis against a percentage of the total pores measured on the Y axis. The lines in
`
`the graph show what percentage of the total pores measured have a given height or
`
`width.
`
`30.
`
`In the plot in Exhibit 1160, the dashed line with square points shows
`
`the distribution of elliptical pore heights. For example, this line shows that
`
`
`
`approximately 35% of the pores measured have a height of approximately 255 nm.
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`10
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 14
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`
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`Similarly, the dashed line with triangle points shows the distribution of elliptical
`
`pore widths. For example, this line shows that approximately 35% of the pores
`
`measured have a width of approximately 455 nm.
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`31. The solid line with diamond points shows the distribution of
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`equivalent circular pore diameters. Essentially, if one were to reshape the
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`elliptical-shaped pores into circular-shaped pores while retaining the same area,
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`this line would show the approximate diameter of the circular pores. The points on
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`this line are equivalent to the average of the corresponding values for the heights
`
`and widths. For example, the solid line shows that approximately 35% of the pores
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`measured would have an equivalent circular pore diameter of approximately 355
`
`nm.
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`32.
`
`I have also included below an annotated version of the image in
`
`Exhibit 1153 (attached as Exhibit 1161), which I created to show the
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`interconnected particles and pores in the sample. The green curved lines in the
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`annotated image identify exemplary pairs of particles that are interconnected. The
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`rightmost green curved line shows that the interconnected particles establish the
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`outer boundary of a pore. Several exemplary interconnected pores are identified
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`by the red curved lines.
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`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`11
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 15
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`33.
`
`I subsequently measured the pore sizes of samples H2, H3, H5, and
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`H6 using the SEM images for each sample and the micron scale bar shown in the
`
`image. I measured the diameter of each pore in the upper right quadrant of the
`
`image (for samples H2 and H3, I also measured the pores in the upper left quadrant
`
`in order to have equivalent statistical robustness) using a ruler in the same manner
`
`as described above for sample H4. Consistent with my expectations, the pore sizes
`
`in these samples are on the same order as the pore sizes in H4.
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`12
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 16
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`34. Specifically, H2 has the following pore dimensions:
`
`•
`
`•
`
`•
`
`Average Elliptical Aspect Ratio: 1.665:1
`
`Mean Pore Width: 470 nm
`
`Mean Pore Height: 270 nm
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`• Width Range: 65-845 nm
`
`•
`
`Height Range: 40-490 nm
`
`I have attached a version of the image containing my annotations as Exhibit 1162.
`
`I have attached the pore size distribution curve I created from the raw data as
`
`Exhibit 1163.
`
`35. H3 has the following pore dimensions:
`
`•
`
`•
`
`•
`
`Average Elliptical Aspect Ratio: 1.817:1
`
`Mean Pore Width: 320 nm
`
`Mean Pore Height: 180 nm
`
`• Width Range: 65-710 nm
`
`•
`
`Height Range: 35-390 nm
`
`I have attached a version of the image containing my annotations as Exhibit 1164.
`
`I have attached the pore size distribution curve I created from the raw data as
`
`Exhibit 1165.
`
`36. H5 has the following pore dimensions:
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`13
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`
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 17
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`
`
`
`
`•
`
`•
`
`•
`
`Average Elliptical Aspect Ratio: 1.667:1
`
`Mean Pore Width: 280 nm
`
`Mean Pore Height: 160 nm
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`• Width Range: 65-690 nm
`
`•
`
`Height Range: 40-415 nm
`
`I have attached a version of the image containing my annotations as Exhibit 1166.
`
`I have attached the pore size distribution curve I created from the raw data as
`
`Exhibit 1167.
`
`37. H6 has the following pore dimensions:
`
`•
`
`•
`
`•
`
`Average Elliptical Aspect Ratio: 1.786:1
`
`Mean Pore Width: 320 nm
`
`Mean Pore Height: 180 nm
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`• Width Range: 65-705 nm
`
`•
`
`Height Range: 35-395 nm
`
`I have attached a version of the image containing my annotations as Exhibit 1168.
`
`I have attached the pore size distribution curve I created from the raw data as
`
`Exhibit 1169.
`
`
`
`
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`14
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 18
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`
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`2. Hydrostatic Weighing
`
`38.
`
`I also measured the density and porosity of sample H4 by hydrostatic
`
`weighing. Hydrostatic weighing is a standard analytical technique used for
`
`measuring porosity of porous ceramic materials, and is the same technique I used
`
`to determine apparent density and apparent porosity that I reported in my Ruys
`
`1993a publication. The results of hydrostatic weighing of samples from my prior
`
`work in 1993 are shown in Figure 2 of the Ruys 1993a publication. In general,
`
`hydrostatic weighing involves filling the pores of a porous material with water (or
`
`other liquid medium) using a vacuum technique (which evacuates air from the
`
`porous material followed by immersion in liquid) or a boiling technique (which
`
`similarly removes air from the porous material, allowing the pores to fill with
`
`liquid). This enables three weights to be measured: the Suspended Weight "S" (the
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`weight of the sample when suspended in water, which will be the least due to the
`
`buoyancy of the material in the liquid); the Saturated Weight "W" (the weight of
`
`the sample when saturated with water); and the Dry Weight "D" (the weight of the
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`sample when dry). These weights S, W, and D, in combination with the known
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`true density of the material, are used in standard equations to arrive at
`
`measurements for the apparent porosity, closed porosity, total porosity, apparent
`
`density, and percent density.
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`15
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`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 19
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`
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`39. Using the hydrostatic weighing technique, I determined that sample
`
`H4 has a suspended weight S of approximately 0.66 grams. I determined that
`
`sample H4 has a saturated weight W of approximately 1.19 grams. Finally, I
`
`determined that sample H4 has a dry weight D of approximately 0.99 grams.
`
`40. Using my hydrostatic weighing measurements and standard
`
`calculations, I determined the apparent porosity (which measures interconnected
`
`pores that are accessible by fluid from the surface) of sample H4 to be 37.7%. I
`
`also calculated the apparent density of sample H4 to be 1.87 g/cm3 and using the
`
`known true density of HA, I calculated the percent density of sample H4 to be
`
`59.2%, from which I calculated the total porosity to be 40.8%. From this I
`
`calculated closed porosity (which measures pores not accessible from the surface)
`
`to be 3.1%. The measurements and calculations can be found in my laboratory
`
`notebook attached as Exhibit 1144.
`
`41. To calculate how much of the porosity is open and interconnected, I
`
`divided the apparent porosity by the total porosity, which is 92.4%. In other
`
`words, 92.4% of the porosity in the sample is from open and interconnected pores,
`
`which also means that 92.4% of the porosity of the sample is, by definition,
`
`connected in some way to the sample surface. From this, I concluded that there is
`
`a uniform interconnected pore distribution throughout the sample. It also confirms
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`16
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 20
`
`
`
`
`
`the visual analysis I described above, which showed that the pores were
`
`interconnected.
`
`3.
`
`Nano-CT
`
`42.
`
`I also conducted a Nano-CT experiment using a Xradia NanoXCT-
`
`100 Nano-Computed Tomographer. Nano-CT uses high resolution scanning to
`
`non-destructively obtain 3-dimensional visualizations of small samples. Generally,
`
`the instrument uses x-rays to create images of cross sections of an object. The
`
`cross sections are analyzed by a computer, which uses an algorithm to process the
`
`cross sections and recreate a virtual model of the object. This allows one to "see"
`
`inside of an object without cutting it open.
`
`43.
`
`I conducted nano-CT analysis on sample H4. I created a digital
`
`animation of the nano-CT analysis for sample H4. A still image taken from this
`
`animation is attached to this declaration as Exhibit 1170. The file containing the
`
`animation is also attached as Exhibit 1171.
`
`44. The still image from my nano-CT animation in Exhibit 1170 presents
`
`a 3-dimensional model of the sample. The model shows that the sample contains
`
`interconnected pores. The regions shown in blue are regions containing
`
`interconnected pores. The small areas that are colored in a different color are
`
`regions with closed pores. As the still image of the model demonstrates, the great
`
`majority of the sample contains interconnected pores, and the pores appear to span
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`17
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 21
`
`
`
`
`
`the entire width of the specimen in all directions. This verifies qualitatively that
`
`my 92.4% open porosity measurement obtained using hydrostatic weighing is
`
`accurate.
`
`4.
`
`Summary
`
`45.
`
`In summary, following the method set forth in the Ruys 1993a
`
`publication, I prepared samples of silicon-substituted calcium phosphate materials.
`
`I analyzed the resulting materials using: (1) SEM; (2) Hydrostatic Weighing; and
`
`(3) Nano-CT. Based on these analytical techniques, I have determined that the
`
`representative sample material that I analyzed possessed the following
`
`characteristics:
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`
`a mean pore width of 455 nm;
`
`a mean pore height of 255 nm;
`
`an average elliptical pore aspect ratio of 1.845:1;
`
`a width range of 65-715 nm;
`
`a height range of 35-385 nm;
`
`interconnected particles; and
`
`a 92.4% open and interconnected porosity, which is further supported
`
`qualitatively by nano-CT analysis showing a sample with a highly
`
`interconnected, porous microstructure.
`
`
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`18
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 22
`
`
`
`
`
`APPENDIX A
`
`MATERIALS CONSIDERED BY Professor Andrew J. Ruys
`
`1144.
`1145.
`1146.
`1147.
`1148.
`1149.
`1150.
`1151.
`1152.
`1153.
`1154.
`1155.
`1156.
`1157.
`1158.
`1159.
`1160.
`
`1161.
`1162.
`1163.
`
`Exhibit No. Reference Name
`1011.
` A.J. Ruys, A Feasibility Study of Silicon Doping of
`Hydroxyapatite, 42 INT’L CERAMIC REV. 372 (1993)
` Ruys Declaration Exhibit – Laboratory Notebook
` Ruys Declaration Exhibit – Image of Samples
` Ruys Declaration Exhibit – Image of Sample H1
` Ruys Declaration Exhibit – Image of Sample H1
` Ruys Declaration Exhibit – Image of Sample H1
` Ruys Declaration Exhibit – Image of Sample H2
` Ruys Declaration Exhibit – Image of Sample H2
` Ruys Declaration Exhibit – Image of Sample H3
` Ruys Declaration Exhibit – Image of Sample H3
` Ruys Declaration Exhibit – Image of Sample H4
` Ruys Declaration Exhibit – Image of Sample H4
` Ruys Declaration Exhibit – Image of Sample H5
` Ruys Declaration Exhibit – Image of Sample H5
` Ruys Declaration Exhibit – Image of Sample H6
` Ruys Declaration Exhibit – Image of Sample H6
` Ruys Declaration Exhibit – Annotated Image of Sample H4
` Ruys Declaration Exhibit – Pore Size Distribution Curve for
`Sample H4
` Ruys Declaration Exhibit – Annotated Image of Sample H4
` Ruys Declaration Exhibit – Annotated Image of Sample H2
` Ruys Declaration Exhibit – Pore Size Distribution Curve for
`Sample H2
` Ruys Declaration Exhibit – Annotated Image of Sample H3
` Ruys Declaration Exhibit – Pore Size Distribution Curve for
`Sample H3
` Ruys Declaration Exhibit – Annotated Image of Sample H5
` Ruys Declaration Exhibit – Pore Size Distribution Curve for
`Sample H5
` Ruys Declaration Exhibit – Annotated Image of Sample H6
` Ruys Declaration Exhibit – Pore Size Distribution Curve for
`Sample H6
`
`1164.
`1165.
`
`1166.
`1167.
`
`1168.
`1169.
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`19
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 23
`
`
`
`
`
`Exhibit No. Reference Name
`1170.
` Ruys Declaration Exhibit – Image of Nano-CT analysis
`1171.
` Ruys Declaration Exhibit – Nano-CT Animation
`
`
`
`
`
`Declaration Of Andrew J. Ruys
`Regarding U.S. Patent Nos.
`RE41,251 and 6,585,992
`
`20
`
`
`
`Baxter Healthcare Corp., et al. v. Millenium Biologix, IPR2013-00590, Exhibit 1135, p. 24
`
`
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