PATENT
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`Attorney Docket No. 22773-826401
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In re Application:
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`Confirmation No.: 5936
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`Inventor:
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`Chunhua Li et a1.
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`Examiner:
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`Caroline Montiel
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`Application No.:
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`15/476,655
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`Group Art Unit:
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`1748
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`Filing or 371 (0) date: March 31, 2017
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`Customer No.
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`107046
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`Title: MULTILAYER DENTAL
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`DECLARATION OF CHUNHUA LI
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`figfigfigifigflggfigm
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`UNDER 37 C.F.R. §1.132
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`
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`Mail Stop Amendments
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`Commissioner for Patents
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`PO. Box 1450
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`Alexandria, VA 223 13-1450
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`DECLARATION OF CHUNHUA LI, PH.D.
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`Commissioner:
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`1, Chunhua Li, declare as follows:
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`I.
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`QUALIFICATIONS
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`1.
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`My name is Chunhua Li. I am the Senior Director of Materials and Biomechanical
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`Engineering at Align Technology, Inc. I have over 25 years of experience in materials and
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`biomechanical engineering, including over a decade designing, developing, and testing materials for
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`dental and orthodontic use.
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`I have worked at Align Technology, Inc., for the past 15 years, before
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`which, I spent seven years working for Abbott Laboratories, and three years working for Cygnus,
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`Inc. While at Align, I have been listed as a co-inventor on at least 24 issued US patents related to
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`dental and orthodontic applications. I hold a PhD degree from the Donghua University in Polymer
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`Engineering. A copy of my curriculum vitae is attached as Appendix A.
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`II.
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`SCOPE OF REVIEW
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`2.
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`I am familiar with the US 15/476,655 patent application (the “’665 application”), on which I
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`am listed as a co-inventor, including the currently pending claims. I have also reviewed the Office
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`Action having a mail date of March 14, 2019, and understand the rejections made in it. I have been
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`informed that the Office Action rejects the claims as allegedly being obvious over Chen et al., US
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`2009/0246724 (referred to herein as “Chen”) in View of DeSimone et al., US 7,641,828 (referred to
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`herein as “DeSimone”), and with regard to thefeatures of claim 26, further in view of Hostettler, US
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`4,791,156 (referred to herein as “Hostettler”). The Office Action at page 5 states that, “It would have
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`been obvious to one of ordinary skill in the art at the time of invention to utilize the materials of
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`DESIMONE to form the hard polymer layer in CHEN since DESIMONE teaches that such materials
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`for the intended use of such hard layers with predictable results and/or reasonable expectation of
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`success.”
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`3.
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`I am also listed as a co-inventor of Chen, which is the primary reference cited by the
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`Examiner in the pending Office Action. I also collaborated closely with Joseph M. DeSimone and
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`Robert E. Tricca (the inventors listed on DeSimone) while they were developing and patenting the
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`technology described in DeSimone. It is my opinion that it would not have been obvious to one of
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`ordinary skill in the art to use the materials taught by DeSimone to form the layered material
`described in Chen, at least because there would have been no reasonable expectation of sucCess in
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`making the combination. Moreover, the appliances recited in the claims of the ’665 application
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`exhibit unexpectedly positive results over previously known appliances. These unexpected results
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`are evidenced by clinical studies that were performed comparing the efficacy of orthodontic
`appliances as described and claimed in the ’665 application with that ofpreviously known
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`appliances. The details of those studies are provided below.
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`

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`III.
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`NOT PREDICTABLE
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`4.
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`Several years ago, Align Technology set out to develop a product that could replace its
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`single-layer, thermoplastic polyurethane appliance product (referred to herein as “EX30”). At the
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`time, EX30 appliances were the standard of care for orthodontic treatment; for example, paragraph
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`[0003] of Chen describes EX30 appliances when it states that “[s]ome dental appliances are made
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`using .
`.
`. thermoplastic polyurethane.” Over the course of more than seven years, Align worked
`diligently to develop a suitable appliance that would meet various criteria for effective orthodontic
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`treatment. During this development process, my team evaluated, in an iterative fashion, more than
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`250 distinct materials and/or material combinations for possible use in an improved appliance. After
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`years of development, Align produced the SmartTrackTM material (also referred to herein as
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`“ST30”), which is a product according to the current claims comprising a multilayered material with
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`a hard polymer layer between two soft polymer layers. We found that the materials with both hard
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`and soft polymer layers according to the current claims in orthodontic appliances had surprisingly
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`superior properties of elongation, time stress-relaxation, durability, and thermoform ability. Each of
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`these properties is important for the production of appliances to apply orthodontic, teeth-moving
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`forces in an oral environment. I would expect that the presence of only two such layers (i.e., a hard
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`polymer layer and a soft polymer layer according to the current claims) would also provide
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`beneficial and Surprisingly superior properties of elongation, time stress—relaxation, durability, and
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`thermoform ability.
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`5.
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`Data obtained by Align during its development of the SmartTrack material provides
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`significant evidence that the effectiveness of the SmartTrack material was unpredictable and
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`unexpected. As mentioned above, the SmartTrack material was developed during more than seven
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`years of diligent evaluation of over 250 materials, including numerous iterations in which materials
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`were tested and compared, with the results used to design new materials. During evaluation of the
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`over 250 materials, only the materials according to the current claims met Align’s development
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`criteria. Among those 250 materials tested were more than 180 materials either generically or
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`specifically described in Chen and/or DeSimone, including various copolymers (Chen at [0036]) and
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`unblended polysulfones (DeSimoneat 6:47-59), as well as styrenic polymer materials such as
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`acrylonitrile-butadiene—styrene (ABS) (id. at 6:24-37). Specifically, none of the 23 copolymers that
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`were tested during the iterative development process met Align’s criteria. Similarly, none of the
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`styrenic polymers nor unblended polysulfones tested met Align’s criteria. Thus none of these
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`materials would have yielded an orthodontic device having sufficient elongation, time stress-
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`relaxation, durability, and thermoform ability.
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`6.
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`In the course of developing the ST3O material, we evaluated numerous multilayer material
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`combinations and determined that merely combining the materials into multiple layers was
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`insufficient to improve performance relative to the EX30 material. In fact, many multilayer materials
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`tested proved inferior to the EX30 material. Some of the multilayer materials that proved inferior to
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`the EX30 material included combinations of materials disclosed in Chen and/or DeSimone. In
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`particular, the sole exemplified multilayer material described in Chen would not be expected to show
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`improved performance relative to EX30. For example, Chen paragraph [0032] describes a material
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`containing polycarbonate and polyvinyl chloride (PVC); however, PVC was later evaluated by my
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`team and found to be unsuitable for use in orthodontic aligners due to its inadequate durability.
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`Based on these tests, we determined that materials containing PVC, either alone or in a multilayer
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`configuration, would be inferior to EX30. For these reasons, a person of ordinary skill would not
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`necessarily expect the addition of multiple material layers, either in general or as particularly
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`described in Chen, to achieve performance superior to EX30.
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`' 7.
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`In my opinion, the fact that the many materials tested did not perform to the level of the
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`desired criteria, either as single or multiple layers, and the fact that a multilayer material combining
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`hard polymer layer and soft polymer layers according to the current claims provided unexpectedly
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`better results than the standard of care at the time of filing, highlights the lack of predictability in the
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`art.
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`IV.
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`NO REASONABLE EXPECTATION OF SUCCESS
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`8.
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`I disagree with the Examiner’s assertion that a person of ordinary skill in the art would have
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`had a reasonable expectation of success in combining the teachings of Chen and DeSimone to arrive
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`at the invention described in the claims of the current application.
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`

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`9.
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`As discussed above, I am a co—inventor of Chen, which is the primary reference cited by the
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`Examiner in the pending Office Action. I was thus intimately familiar with the teachings of Chen
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`during the development of the currently claimed orthodontic appliances. I also collaborated closely
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`with Joseph M. DeSimone and Robert E. Tricca (the inventors listed on DeSimone) while they were
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`developing and patenting the technology described in DeSimone. I was thus very aware of the
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`teachings of DeSimone during the development of the orthodontic appliances according to the _
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`current claims. Even with my extensive knowledge of the teachings of Chen and DeSimone, it took
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`me and my team over seven years to identify the combination of polymers for the claimed multilayer
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`orthodontic appliance. Thus, I disagree that it would have been obvious to one of ordinary skill in
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`the art to use the materials taught by DeSimone to form the layered material described in Chen.
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`10.
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`Indeed, the fact that the over 250 materials tested by my team did not provide results meeting
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`the desired criteria, while the SmartTrack material as described in the current claims was found to
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`meet Align’s criteria for a multilayer appliance, itself suggests that there was no predictability and
`there would have been no reasonable expectation of success in combining the teachings of Chen and
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`DeSimone. If anything, a person of ordinary skill in the art would have expected failure in light of
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`the above-described development history.
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`V.
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`CLINICAL STUDY RESULTS
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`11.
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`Align conducted a clinical study demonstrating the superior performance of multilayered
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`orthodontic appliances as described in the current claims. The clinical study compared the
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`performance of clear plastic appliances made with Align Technology’s SmartTrack material (ST30),
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`which is an appliance according to the current claims comprising a layered material with a hard
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`polymer layer between two soft polymer layers, to appliances made of thermoplastic polyurethane
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`(EX30), which was the standard clear plastic material in appliances on the market at the time of the
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`clinical study, and was made of a single-layered material. Patients in the study were assigned to one
`of two groups—an Experimental Group or a Control Group. The Experimental-Group received
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`Invisalign Assist appliances made with the SmartTrack material (ST3 0), while the Control Group
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`received appliances made with thermoplastic polyurethane (EX30). The methods of treatment for
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`each group were otherwise the same. The Experimental Group consisted of all new Invisalign Assist
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`orthodontic cases for a one-month period, totaling 1,015 patients, and the Control Group consisted of
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`all patients from the immediately preceding six-month period. The study followed a double-blind
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`protocol in which neither treating doctors nor patients were informed of their group assignment.
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`12.
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`Because appliances made of the EX30 material were the standard of care during our
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`development of the SmartTrack material and were superior to many multilayer materials tested, we
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`considered the EX30 material to be the most reasonable comparative material when performing
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`clinical trials of the SmartTrack material.
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`13.
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`Patients in the study were tracked over a five-month period, during which time, the patients
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`were provided with clear plastic orthodontic appliances appropriate to their group of the study, and
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`configured to produce a prescribed target movement of one or more teeth. Impressions of patient
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`teeth were taken at the beginning and end of the treatment period, and measured amounts of tooth
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`movement were compared to target amounts of tooth movement. Patients were placed into one of
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`three groups based on the measured movement of teeth: On-Track, Off-Track, or Cannot Match.
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`Patients were assigned to On-Track if the measured tooth movement matched the target tooth
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`movement to within a predetermined degree of variance, based on the conclusion of the treating
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`doctor or on direct analysis of data from doctor-submitted impressions. Patients with tooth
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`movement falling outside this range were classified as Off-Track. Patients far outside the range were
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`classified as Cannot Match.
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`14.
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`Patients treated with ST30 appliances showed significantly superior outcomes compared to
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`patients treated with EX30 appliances in various indicia. Specifically, the Experimental Group
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`(ST30) had 26% more On-Track patients than the Control Group (EX30), representing a strongly
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`significant improvement (p < 0.001). Similar improvements were measured in the other groups, with
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`fewer patients in the Experimental Group than the Control Group in both the Off—Track (—17%, p <
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`0.001) and Cannot Match (-34%, p < 0.001) categories.
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`15.
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`In the above-described clinical study, the ST30 appliances contained a hard polymer layer,
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`which provided the forces needed to generate movement of the teeth, While the soft polymer layers
`increased the durability 'of the aligners allowing them to better Withstand wear due to aligner
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`reinsertion and removal and other mechanical stresses put on the aligner during treatment as well as
`
`improving the elastic properties allowing for less degradation in the shape of the teeth receiving
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`-6-
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`cavities. A combination of a single hard polymer layer and a single soft polymer layer according to
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`the current claims would also exhibit these beneficial functions in an appliance. Thus, I would also
`expect an appliance with layers of a single hard polymer material and a single soft polymer material
`
`according to the current claims to exhibit beneficial performance relative to EX30 appliances.
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`16.
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`A retrospective analysis was performed providing further evidence of the superior
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`performance of materials combining a hard polymer layer with a soft polymer layer, such as
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`SmartTrack, as recited in the current claims. From a patient population of over two million
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`individuals over a six-year period, 110,000 cases with both initial and secondary dental scans were
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`randomly selected from the Invisalign patient database. The Experimental Group had 58,000 cases
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`using appliances comprising ST30 material, while the Control Group had 52,000 cases using
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`appliances comprising EX30 material. Tooth Movement Predictability was measured by comparing
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`achieved versus planned tooth movement, with higher predictability corresponding to smaller
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`deviations from planned movement. Improvement in Tooth Movement Predictability between
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`groups was defined. as: 100% x (Experimental Group Predictability - Control Group Predictability)
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`/( Control Group Predictability ). Predictability improvement was measured for a total of fourteen
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`criteria based on type of movement (e.g., rotation, extrusion, and root tip movement) and type of
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`tooth. Each measured movement type showed strongly significant improvement for the Experimental
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`Group over the Control Group (p<0.001). Appendix B summarizes these results.
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`17.
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`Asa weighted average, the Experimental Group (ST30) showed greater than 75%
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`improVement in overall tooth movement predictability over the Control Group (EX30). As EX30
`appliances were the standard appliances used for orthodontic treatment up until the release of ST30,
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`a person of ordinary skill in the art would expect that significantly superior performance relative to
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`EX30 would translate to similarly superior performance relative to other orthodontic appliances,
`including some multilayered appliances. Accordingly, the use of a multilayered material comprising
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`materials as described in the current application (e.g., with hard polymer and soft polymer layer
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`according to the current claims) represents a large and significant improvement over the prior art. In
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`my opinion, a person of ordinary skill in the art would not have expected this result based on the
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`teachings of the prior art.
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`

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`18.
`
`In the above-described retrospective analysis, the ST30 appliances contained a hard polymer
`
`layer, which provided the forces needed to generate movement of the teeth, while the soft polymer
`
`layers increased the durability of the aligners allowing them to better withstand wear due to aligner
`
`reinsertion and removal and other mechanical stresses put on the aligner during treatment as well as
`
`improving the elastic properties allowing for less degradation in the shape of the teeth receiving
`
`cavities. A combination of a single hard polymer layer and a single soft polymer layer according to
`
`the current claims would also exhibit these beneficial functions in an appliance. Thus, based on the
`
`work performed by our team, one would also expect an appliance with layers of a single hard
`
`. polymer material and a single soft polymer material according to the current claims to exhibit
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`beneficial performance relative to EX30 appliances.
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`VI.
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`UNEXPECTED EFFICACY 0F SMARTTRACK MATERIALS
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`19.
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`The above-described clinical studies demonstrate the significantly improved performance of
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`materials containing a combination of hard polymer and soft polymer layers according to the current
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`claims, such as SmartTrack, relative to the previous standard of care in orthodontic treatment with
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`clear plastic appliances (EX30)—a surprising result that would not have been expected by a person
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`of ordinary skill in the art. Prior to the development of appliances using SmartTrack materials,
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`virtually all clear plastic orthodontic appliances sold in the United. States were made with the
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`materials used in the appliances of the Control Groups (EX3 0). As a result of SmartTrack’s
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`dramatically improved performance over EX30 appliances, SmartTrack appliances became the new
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`standard for aligners produced by Align Technology. In fact, the results of the clinical comparisons
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`between EX30 and ST30 materials were so striking that Align made an unprecedented, nearly
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`complete switch in the US. from thermoplastic polyurethane (EX3 O) appliances to SmartTrack
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`(ST30) appliances within a matter of only months. SmartTrack appliances now account for over 90%
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`of the total US. market for clear plastic orthodontic appliances from all sellers. See, e.g., Baird 2014
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`Analyst Report at 6 (“93% share of the $550 million clear aligner orthodontic market segment”), see
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`also Baird Q3 2013 Report at 9.
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`20.
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`The effectiveness of appliances made with multilayered materials combining hard polymer
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`and soft polymer layers (e.g., SmartTrack) was surprising, and a person of ordinary skill in the art
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`would not. have predicted the improved performance demonstrated in the above clinical study. In
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`particular, a person of ordinary skill in the field would not have expected the significantly improved
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`clinical performance of these multilayer materials, such as SmartTrack, compared to the prior art.
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`21.
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`I declare that all statements made herein are true to the best of my knowledge, and that all
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`statements made on information and belief are believed to be true; and further that these statements
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`were made with the knowledge that willful false statements and the like so made are punishable by
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`fine or imprisonment, or both, under section 1001 or Title 18 of the United States Code, and that
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`such willful false statements may jeopardize the validity of the application or any patent issued
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`thereon.
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`Executed on this 16th day of September, 2019
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`fl»
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`Chunhua Li, PhD.
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`Appendix A —— Curriculum Vitae of Chunhua Li, Ph.D.
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`PROFESSIONAL EXPERIENCE:
`
`Align Technology, Inc., San Jose, CA
`2015 - Present: Sr. Director, Materials Engineering and Biomechanics
`
`Director, Materials Engineering and Biomechanics (2011-2015)
`Sr. Manager, Materials Engineering (2007-2011)
`Manager, Materials Engineering (2003 -2007)
`
`0 Leading a team of biomechanical, materials engineering, product requirements, product analytics
`and software engineering for product research and development of the Invisalign system and
`related products
`- Responsible for R&D product research and development functional area, leading, planning and
`execution of Invisalign product development projects and managing resources to meet company
`roadmap commitments
`- Directing product planning, resources and strategy, working with cross functional team including
`marketing, clinical, operation, legal and regulatory. Managing product development cycle from
`conceptual, product launch to global regulatory submissions
`0 Working with internal and external technology leaders, developing next generation
`technology/materials for orthodontic medical device, working on cutting edge technologies such
`as 3D printing materials/technologies, addressing all technical challenges to bring new
`technology/material from concept to suCcessfiil product launches
`
`Abbott Laboratories, Hospital Products Division, Morgan Hill, CA
`1996 - 2003: Sr. Staff Engineer
`0 Technical expert for the R&D department in material selection, evaluation, characterization and
`failure analysis for electro—mechanical and disposable medical devices
`0 Developed an antimicrobial-eluting catheter coating, from technology assessment and evaluation,
`through product development, in-vitro and in-vivo animal testing, writing a 510(k), and
`transferring the technology into manufacturing
`0 Conducted technical assessments and recommendations for new medical device in the field of
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`cardiology, critical care and oncology, products evaluated include catheters, stent coatings,
`vascular hemostatic devices and drug delivery systems
`- Assessed customer complaints on a disposal medical device, re-formulating a polymer
`compound and modifying the extrusion to provide a customer preferred product; Investigated a
`field failure of fiber optic pulmonary artery catheters, identifying the root cause, and providing a
`method for process improvement/control. Received “Abbott Chairman’s Award” in 1997
`Set up polymer characterization lab, and provided material characterization and problem solving
`to internal customers. Supported manufacturing sites on material- related issues and cost
`reduction
`'
`
`0
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`-10-
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`

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`Cygnus Inc., Redwood City, CA
`1993 - 1996: Group Leader/Research Scientist
`I Managed an analytical group of 8 chemists in the analysis of contrOlled release drug products
`and raw materials for product release and stability assessment. Responsible for analytical data,
`method validation, instrument qualification, analytical procedure and interacted with different
`functions across the organization to provide analytical support
`- Conducted polymer characterization using GPC (triple detector), DMA, DSC, TGA and other
`
`mechanical measurements
`
`0 Provided technical support for material evaluation on various polymeric materials used in
`transdermal drug delivery systems
`- Conducted research on chemical composition and curing mechanisms of pressure sensitive
`adhesives in transdermal drug delivery systems
`Studied the interactions among different ingredients in the transdermal drug delivery system,
`leading to the development of a more stable system and a patent
`
`0
`
`Penederm Inc., Foster City, CA
`1991 - 1993: Research Scientist
`-
`Synthesized polymers and compounds for topical drug delivery systems; scaled up candidate
`polymers from lablto production
`- Characterized polymer structures and properties by GPC, FTIR, GC, HPLC and DSC
`o
`Screened polymers according to their properties for topical, mucosal and cosmetic applications;
`conducted investigations into new areas of research such as hydrogels and muco-adhesives
`o Responsible for training personnel on instrumental operations and laboratory safety techniques,
`radiation protection principles and decontamination control
`
`Stanford University, Department of Chemical Engineering, Palo Alto, CA
`June 1991 — Oct. 1991: Research Assistant
`
`- Conducted research on polymer rheological properties
`
`EDUCATION:
`
`Ph. D. in Polymer Engineering, Dong Hua University, Shanghai, China
`Thesis: Microphase Separation and Surface Modification of Segmented Polyurethanes
`BS in Chemistry, Dong Hua University, Shanghai, China
`
`PUBLICATIONS AND PATENTS:
`
`24 US issued patents on dental and orthodontic application fields:
`
`US Pat. Nos. 7,553,157; 7,766,658; 7,824,180; 7,854,609; 7,878,801; 7,883,334; 7,947,508;
`
`8,075,309; 8,439,674; 8,708,697; 8,758,009; 8,765,031; 8,899,976; 9,241,774; 9,597,164; 9,655,691;
`
`9,655,693; 9,730,769; 9,744,001; 9,844,424; 10,052,176; 10,154,889; 10,201,409; and 10,299,894.
`
`-11-
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`Appendix B — Retrospective study data showing the degree of improvement in tooth movement
`predictability for various categories of tooth movement (e.g., rotation, extrusion, and root tip
`movement) in the Experimental Group (ST30) relative to the Control Group (EX30). Each
`measured movement type showed strongly significant improvement in predictability for the
`Experimental Group over the Control Group (p<0.001).
`w,
`
`>5
`
`x
`
`
`
`
`
`
`
`
`
`
`
`
`1 8%
`<0.001
`
`
`1
`
`60%
`
`<0.001
`
`Upper Canine Rotation3
`
`Upper Premolar Rotation
`
`81 194
`,
`
`10 401
`
`
`
`
`
`
`
`
`
`
`
`
`
`' “Improvement” refers to the extent of increase in tooth movement predictability for the
`Experimental Group (ST30) relative to the Control Group (EX30).
`
`2 “P-Value” is also known as “calculated probability” and is a measure of statistical significance
`of an observed result, with P—Values of less than 0.001 being statistically highly significant, i.e., less
`than 0.1% probability of the observed result being a chance occurrence.
`
`3 “Rotation” is defined as the turning of a tooth around its longitudinal axis.
`
`4 “Extrusion” is defined as elongation of a tooth or movement of a tooth in an occlusal or incisal
`direction.
`
`5 “Root Movement” is defined as a condition in which the root of a tooth moves in the direction
`of force but the crown position remains the same or is only minimally displaced.
`
`-12-
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