Regents of the University of California v. I-MED Pharma Inc.

Regents of the University of California v. I-MED Pharma Inc.
Court (s) Database
Federal Court Decisions
Date
2018-02-12
Neutral citation
2018 FC 164
File numbers
T-300-16
Notes
A correction was made on March 12, 2018.
Decision Content
Date: 20180212
Docket: T-300-16
Citation: 2018 FC 164
Ottawa, Ontario, February 12, 2018
PRESENT: The Honourable Mr. Justice Manson
BETWEEN:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA and TEARLAB CORPORATION
Plaintiffs
(Defendants by Counterclaim)
and
I-MED PHARMA INC.
Defendant
(Plaintiff by Counterclaim)
JUDGMENT AND REASONS
Table of Contents
I. Pleadings 3
II. Summary of Results 4
III. Background 5
A. The Parties 5
B. Technological Background 6
(1) Scientific Primer 6
(2) The ‘540 Patent 8
(3) The i-Pen 11
IV. Plaintiffs’ Fact Witnesses 12
A. Mr. Paul Smith 12
B. Dr. Ben Sullivan 14
V. Plaintiffs’ Expert Witnesses 19
A. Dr. James Wolffsohn 19
B. Dr. Brian Kirby 21
VI. Defendant’s Fact Witnesses 22
A. Mr. Daniel Hofmann 22
B. Mr. Zvi Nachum 26
VII. Defendant’s Expert Witnesses 29
A. Dr. Manfred Franke 29
VIII. Preliminary Issues 30
A. TearLab’s Standing 30
IX. Claim Construction 30
A. Principles 30
B. Relevant Dates 31
C. The Person of Ordinary Skill in the Art 32
D. Common General Knowledge 33
(1) Principles 33
(2) Prior Art 37
E. Claim Construction 45
(1) “Sample receiving chip” 45
(2) “Substrate that receives an aliquot volume of a sample fluid” 46
(3) “A sample region of the substrate whereupon energy properties of the sample fluid can be detected” 47
X. Infringement 48
A. Principles 48
B. Analysis 49
XI. Validity 53
A. Anticipation 53
(1) Principles 53
(2) Analysis 54
B. Gillette Defence 58
(1) Principles 58
(2) Analysis 59
C. Obviousness 60
(1) Principles 60
(2) Analysis 61
D. Utility 63
(1) Principles 63
(2) Analysis 64
E. Sufficiency 65
(1) Principles 65
(2) Analysis 66
XII. Costs 67
I.
Pleadings
[1] This action concerns the validity and enforcement of Canadian Patent No. 2,494,540 entitled “Tear Film Osmometry” (the “‘540 Patent”). The ‘540 Patent was filed on March 25, 2003, issued on June 3, 2014, and expires on March 25, 2023. It grants the patentee the exclusive right in Canada to make, use, import and sell the invention claimed.
[2] The Plaintiffs are the Regents of the University of California (the “University”) and TearLab Corp. (“TearLab”). The Defendant is I-MED Pharma Inc. (“I-MED”).
[3] The University owns the ‘540 Patent. TearLab holds a sub-license from its wholly-owned subsidiary TearLab Research Inc., who holds an exclusive license from the University to, among other things, make, have made, use, sell, offer for sale and import products into Canada that are covered by the claims of the ‘540 Patent.
[4] The Plaintiffs assert that the Defendant’s i-Pen Osmolarity System (the “i-Pen”) infringes claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 of the ‘540 Patent.
[5] The Defendant asserts non-infringement (including the Gillette Defence) and invalidity of each of the claims asserted by the Plaintiffs under the ‘540 Patent, on the basis of anticipation, obviousness, inutility, insufficient disclosure and overbroad and ambiguous claims.
[6] The issues are as follows:
Preliminary issue:
Does TearLab have standing?
Patent infringement and validity
Infringement:
Does the i-Pen infringe any of claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 of the ‘540 Patent?
Does the subject-matter of any of claims 1, 2, 5, 8, 13 and 14 lack novelty?
Was the subject-matter of any of claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 obvious at the claim date?
Do any of claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 fail to demonstrate the utility of the invention?
Did claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 fail to soundly predict the utility of the invention as of the filing date?
Does the specification fail to correctly and fully describe the invention and its operation?
Does the specification fail to set out the invention in such full, clear and concise and exact terms as to enable any person skilled in the art of science to which it pertains?
Does the specification fail to explain the principle of the invention and the best mode in which the inventor has contemplated the application of that principle?
Do claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 fail to define distinctly and in explicit terms the subject-matter of the alleged invention for which an exclusive privilege or property is claimed?
Are claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 directed to a desired result rather than to any invention directed to how to achieve that result?
Are claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 broader than any invention made or disclosed in the ‘540 Patent?
Validity:
Anticipation:
Obviousness:
Utility:
Sufficiency:
Ambiguous claims:
Overbroad claims:
II. Summary of Results
Preliminary issue:
TearLab has standing.
Patent infringement and validity
Infringement
The i-Pen infringes claims 1, 2, 5, 8, 13, 14, 16, 25 and 26 of the ‘540 Patent; it does not infringe claim 6.
Anticipation:
a) Claims 1, 2, 5, 8, 13 and 14 are anticipated.
a) Claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 are obvious.
a) Claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 demonstrate utility.
a) Claims 1, 2, 5, 6, 8, 13, 14, 16, 25 and 26 are sufficient.
a) This issue was abandoned at trial.
a) This issue was abandoned at trial.
Obviousness:
Utility:
Sufficiency:
Ambiguous claims:
Overbroad claims:
Validity:
III. Background
A. The Parties
[7] The University is the owner of the ‘540 Patent.
[8] TearLab is a sub-licensee under the ‘540 Patent. It is incorporated in Delaware and is based in California. TearLab manufactures diagnostic products for eye-care professionals. In particular, it manufactures the TearLab Osmolarity System (the “TearLab System”).
[9] I-MED is a Québec-based company that focuses on human and animal eye care. Among other things, it distributes medical devices, including importing and selling the i-Pen through a distributor in Canada.
B. Technological Background
(1) Scientific Primer
[10] The parties jointly prepared a scientific primer with respect to relevant technology and principles that they agree upon. The primer contains sections on osmolarity, eye and tear film anatomy, dry eye disease and principles of electricity.
[11] Osmolarity refers to the concentration of all dissolved particles, or solutes, in a solution. It can be estimated by the measurement of physical properties that are affected by solute concentration. In 2002, analyses used to estimate osmolarity included freezing point depression, boiling point elevation, vapour pressure depression, osmotic pressure and electrical impedance. The freezing point and vapour pressure of a solution decrease as osmolarity increases, whereas its boiling point increases. Osmotic pressure will differ between solutions that have different osmolarities and are separated by a semi-permeable membrane. Electrical impedance of a solution decreases as its osmolarity increases.
[12] The inner surfaces of the eye are composed of the cornea (the transparent window to our vision), the sclera (the white portion) and the inner sides of the eyelids. The conjunctiva, a mucous membrane, lines the sclera and eyelids. A layer of tear film also covers the inner surfaces of the eye and is composed of three layers. The inner mucin layer is a mixture of proteins that spreads the tear film and holds it to the ocular surface. The intermediate aqueous layer accounts for most of the volume of the tear film, keeps the eye moist, washes away debris and helps with oxygen supply to the cornea. It has a specific level of dissolved nutrients and salts; fresh production by the lacrimal gland and drainage through nasal canals prevents increases in osmolarity that result from evaporation. The outer lipid layer helps spread the tear film and reduce evaporation of the aqueous layer. The primary solutes in tear fluid are ions; therefore, a conductance measurement of tear fluid is closely related to its osmolarity.
[13] Dry Eye Disease (“DED”), also known as keratoconjuctivitis sicca, is a disease of the tears and ocular surface that results in discomfort, visual disturbance and tear film instability, with potential damage to the ocular surface. There are two forms of DED, which both lead to a tear fluid with increased osmolarity: aqueous-deficient dry eye, which refers to reduced tear film secretion from the lacrimal gland; and evaporative dry eye, which refers to excessive evaporation of the tear film. In 2002, four main tools were used to diagnose DED in the clinical setting: (1) Schirmer’s test, a correlation of tear volume with the length of wetting on paper or string; (2) tests of tear film stability, such as the time taken for tear film to break on the ocular surface; (3) ocular surface staining with dyes to assess ocular surface damage; and (4) patient symptoms. The link between tear osmolarity and DED was explored between the 1970s and 1990s; however, measurement of tear osmolarity at that time relied on freezing point and vapour pressure analyses, which were complicated, expensive or required large sample volumes. Those challenges restricted the use of osmolarity as a diagnostic tool in a clinical setting.
[14] Conductivity is an intrinsic property of a material that indicates how well it conducts electricity; the dimensions of the material do not affect conductivity. In contrast, conductance is a holistic property of a system that indicates how well it conducts electricity and is dependent on properties of the system such as mass, size, shape and components. Other relevant principles of electricity include: resistivity (how well a material hinders current); resistance (how well a system hinders current); capacitance (the ability of a system to store an electric charge); reactance (a measure of the opposition of a circuit element in a given system to a change in current or voltage, due to that element’s inductance or capacitance); and impedance (a measure of the opposition that a circuit presents to a current when a voltage is applied). Finally, Ohm’s Law, which is V=IR, describes the relationship between voltage (V), current (I) and resistance (R). In a system with negligible capacitive and inductive effects, an impedance measurement can be treated as the resistance and Ohm’s Law can be applied.
(2) The ‘540 Patent
[15] The ‘540 Patent discloses an invention related to measuring the osmolarity of a sample of a bodily fluid, including particularly tear film, whereby the sample fluid is deposited on a chip. The chip has a substrate and a sample region. The sample fluid is deposited such that it operatively covers the sample region, so that energy imparted to the sample fluid is detected from the sample region to produce an output signal that indicates osmolarity of the sample fluid. As described at page 4, lines 12 to 17 of the ‘540 Patent:
Osmolarity measurement of a sample fluid, such as tear film, is achieved by depositing an aliquot volume of the sample fluid on a microchip having a substrate and a sample region of the substrate, wherein the volume of the sample fluid operatively covers a sufficient portion of the sample region such that energy imparted to the sample fluid is detected from the sample region to produce an output signal that indicates osmolarity of the sample fluid.
[16] The requisite volume of sample fluid can be as low as 1 nl, which can be easily obtained from patients.
[17] Energy transferred to the sample fluid can be electrical, optical or thermal. Electrodes can be installed on the substrate such that the sample fluid bridges the electrodes, and electrical energy passing through the electrodes measures conductivity and is correlated to osmolarity. Alternatively, nanometre-sized spheres can be coated with luminescent ion-sensitive chemicals and then exposed to a sample fluid and excited with light energy, such that the spheres luminesce and emitted light is correlated to osmolarity of the sample fluid. As a further alternative, continuously cooling the sample fluid results in reduced conductivity upon freezing, which allows for correlation of the determined freezing point with the osmolarity of the sample.
[18] The ‘540 Patent also discloses an osmolarity measuring system comprising a sample fluid reception device as well as a platform for data communication. The reception device can be as simple as a set of electrodes on a chip, or as complex as a logic-enabled microprocessor capable of enacting measurement dynamics, and may also be used to control and measure temperature. The platform for data communication receives output from the reception device and interprets and displays osmolarity to the user. In this way, an accurate osmolarity measurement can be obtained with minimum inconvenience, little skill and a high degree of repeatability. As described at page 7, lines 11 to 21 of the ‘540 Patent:
Exemplary embodiments are described for measuring the osmolarity of an aliquot volume of a sample fluid (e.g., tear film, sweat, blood or other fluids). The exemplary embodiments are configured to be relatively fast, non-invasive, inexpensive, and easy to use, with minimal injury of risk to the patient. Accurate measurements can be provided with as little as nanolitre volumes of a sample fluid. For example, a measuring device configured in accordance with the invention enables osmolarity measurement with no more than 20μL of sample fluid, and typically much smaller volumes can be successfully measured. In one embodiment described further below, osmolarity measurement accuracy is not compromised by variations in the volume of sample fluid collected, so that osmolarity measurement is substantially independent of collected volume.
[19] The ‘540 Patent contains four independent claims, only two of which, claims 1 and 16, are being asserted by the Plaintiffs:
Claim 1: a sample receiving chip comprising:
a substrate that receives an aliquot volume of a sample fluid; and
a sample region of the substrate, sized such that the volume of the sample fluid is sufficient to operatively cover a portion of the sample region, whereupon energy properties of the sample fluid can be detected from the sample region to produce an electrical signal comprising a sample fluid reading, wherein the sample fluid reading is related to the sample fluid energy properties and indicates osmolarity of the sample fluid.
Claim 16: an osmolarity measuring system for measuring osmolarity of a sample fluid, the system comprising:
a measurement device comprising a sample receiving chip that includes a substrate having a sample region configured to contact the sample fluid to produce an electrical signal that is related to energy properties of the sample fluid, wherein the region is sized to be substantially covered by an aliquot volume of the sample fluid; and
a processing device coupled to the measurement device, the processing device configured to receive the measured energy properties and to process and estimate the osmolarity of the sample fluid from the processed energy properties.
[20] The following asserted claims are dependent on claim 1:
Claim 2: a chip as defined in claim 1, wherein the sample region includes a plurality of electrodes disposed to contact the sample.
Claim 5: a chip as defined in claim 2, further comprising a plurality of conductive connection lines coupled to the plurality of electrodes, wherein the conductive connection lines provide means for transferring energy to and from the sample fluid.
Claim 6: a chip as defined in claim 5, further comprising:
a processing unit configured to receive energy properties of the sample fluid from the plurality of conductive connection lines, wherein the processing unit processes the received energy properties and outputs the osmolarity of the sample fluid.
Claim 8: a chip as defined in claim 1, wherein area of the sample region on the substrate is less than one centimeter square.
Claim 13: a chip as defined in claim 1, wherein the sample fluid includes bodily fluid.
Claim 14: a chip as defined in claim 13, wherein the bodily fluid is a tear film.
[21] The following asserted claims are dependent on claim 16:
Claim 25: a system as defined in claim 16, wherein the substrate includes an electrical conductivity measurement circuit.
Claim 26: a system as defined in claim 16, wherein the measurement device includes a plurality of electrodes.
(3) The i-Pen
[22] The i-Pen measures the conductivity of the moisture in the eyelid conjunctiva and tear film thereon, and that measurement can be correlated to osmolarity. The measurement is provided by a single use sensor (“SUS”), consisting of a pair of electrodes installed on a non-conducting substrate, which is placed against the moist tissue on the inner surface of an eyelid. When stimulated with electrical current, the moisture completes a circuit between the electrodes and its conductivity is measured by a microprocessor located within the i-Pen. A different SUS is inserted into the i-Pen for each measurement and disposed thereafter.
[23] The i-Pen was approved in Canada as a Class II Medical Device in January 2015; the license was suspended on September 23, 2015, and was reinstated on May 13, 2016.
IV. Plaintiffs’ Fact Witnesses
A. Mr. Paul Smith
[24] Mr. Paul Smith (“Mr. Smith”) is TearLab’s Vice President of Global Sales. Previously, he was Vice President of International Markets. He joined TearLab in April, 2014, after working at another eye-care corporation for 12 years. He stated that TearLab has 75 employees, including 49 in his sales team.
[25] Mr. Smith briefly described the TearLab System. There is a reader base-station, handheld pen and single-use test card. The user attaches the card to the top of the pen and brings the pen in contact with the corner of the eye, at which point the card wicks-up and analyzes a 50 nl sample of tear film. The raw data is stored inside the pen, which is returned to the reader and an osmolarity measurement is reported.
[26] Mr. Smith stated that the TearLab System is primarily used by technicians under the supervision of eye care professionals. It obtained regulatory approval in Europe in 2008 and Canada and the United States in 2009. Sales in Canada began “in earnest” in 2012, but there may have been some sales prior to that year. Currently, the TearLab System is sold in over 50 countries. Since January 2016, TearLab has used an independent distributor in Canada named Labtician Ophthalmics Inc. Worldwide sales total approximately 5,600 systems, of which 4,600 have been in the USA and 100 in Canada.
[27] Mr. Smith explained the corporate structure of TearLab. OcuSense Inc. (“OcuSense”) was a corporation started by Dr. Ben Sullivan in 2008. OcuSense became a wholly-owned subsidiary of OccuLogix Inc. (“OccuLogix”) in 2008. OccuLogix changed its name to TearLab Corp. in 2010. OcuSense has since changed its name to TearLab Inc. and then again to TearLab Research Inc. The result is that TearLab Research Inc. is a wholly owned subsidiary of TearLab Corp. Both corporations are incorporated in Delaware and based in California and Texas.
[28] Moreover, Mr. Smith explained that OcuSense, now TearLab Research Inc., obtained an exclusive license under the ‘540 Patent from the University in 2003. Currently, it makes quarterly royalty payments to the University. As well, TearLab Corp. currently holds an exclusive sub-license from TearLab Research Inc.
[29] Finally, Mr. Smith discussed a clinical study entitled “Randomized Comparison of In Vivo Performance of two Point-of-Care Tear Film Osmometers”, which was published in Clinical Opthalmology, a well-known peer review journal, in May 2017 (the “Nolfi Study”). This study was sponsored by TearLab and was meant to compare the TearLab System and the i-Pen. The two authors are practicing optometrists in Toronto: Dr. Barbara Caffery (“Dr. Caffery”) is president of the American Academy of Optometry; Dr. Jerry Nolfi (“Dr. Nolfi”) was previously a consultant on TearLab’s clinical advisory board and was the principal in a company called Science with Vision Inc., which distributed the TearLab System in the Canadian market for a period of approximately 12-18 months. Dr. Nolfi also owned shares in TearLab at the time the study protocol was developed.
[30] Mr. Smith was cross-examined with respect to the Nolfi Study. He explained that Dr. Manoj Venkiteshwar, from TearLab’s Medical Affairs Department, collaborated with the authors to develop the study protocol. That protocol was under a TearLab letterhead and signed by Dr. Nolfi but not Dr. Caffery. He was not aware of any existing drafts or how the authors provided comments. Mr. Michael Berg, TearLab’s head of regulatory affairs, was not involved in the study except with respect to TearLab’s quality control procedures, which were not specific to the study and which every TearLab customer must adhere to. TearLab was not present during the measurements and does not know who performed them. Since Clinical Ophthalmology is an open-access journal, TearLab paid a fee for the study to be published.
[31] Mr. Smith was a credible witness.
B. Dr. Ben Sullivan
[32] Dr. Ben Sullivan (“Dr. Sullivan”) is the Chief Scientific Officer of TearLab. He studied biomedical engineering at Boston University from 1993-97. After graduation, he worked from 1998-2001 as a research engineer at the Schepens Eye Research Institute, an affiliate of Harvard Medical School. In 2001, he left Schepens and enrolled in the Ph.D. program at the University of California, San Diego, researched DNA and its interactions with fluorescence at the nanoscale level, and obtained a Ph.D. in 2007.
[33] It was during his time at Schepens that Dr. Sullivan became interested in DED. He worked alongside his father, who was researching the hormonal and glandular aspects of DED. Dr. Sullivan recognized the need for a tool to quantitatively measure DED and in particular, a tear osmometer. He began working at home by himself on the development of a tear osmometer.
[34] Dr. Sullivan continued to work on the osmometer concept while working on his Ph.D. He studied under a professor who had access to “lab on a chip” devices used to study DNA. These microchips allowed Dr. Sullivan to more easily perform experiments using tear film and modified electrical signals. His lab set-up was complex and included a microchip, power source, multimeter, computer, LCR meter and other equipment. His goal was to make a portable and inexpensive tear osmometer, given that, in his opinion, while non-commercially viable tear osmometers already existed, they were not clinically available or cost-effective and efficient.
[35] This work lead to the filing of a provisional patent application in August, 2002, which Dr. Sullivan assigned to the University. A breakthrough came in late 2002, when he discovered that using a 100 kHz AC signal (instead of DC) allowed for stable measurements. He was approached by an investor, Mr. Eric Donsky, and OcuSense was incorporated in January, 2003. Later that year, a license was negotiated with the University and marketing materials and a protocol for clinical trials were created.
[36] Clinical trials were performed at the Shiley Eye Research Institute at the University during several months in 2004. In the years following the clinical trials, Dr. Sullivan developed his osmometer down to the size of a lunch tray and OcuSense sought investors. Eventually, the company was purchased by OccuLogix and better equipment was used for product development. Regulatory approval was obtained in Canada, USA and the EU around 2009.
[37] On cross-examination, Dr. Sullivan admitted that in 2001-02, “small volume” could mean 100-200 nl, but that the term is relative. The current TearLab System collects approximately 50 nl. That sample volume is pulled into a channel by capillary action and thereby spread over 3 mm. Regarding the device Dr. Sullivan was working on during the 2001-02 timeframe, a 100-200 nl sample completed an electrical circuit by bridging at least two electrodes on a silicon chip. The electrodes were spaced 40-80 microns apart.
[38] Dr. Sullivan agreed that impedance is affected by the geometry of the fluid and that the electrodes, substrate and sample volume affect the geometry of the fluid. Generally, a sensor placed in tear fluid would produce a different reading from that produced by a drop of fluid on a substrate containing electrodes. He also stated that at a certain scale, impedance becomes relatively volume independent.
[39] Dr. Sullivan also agreed that in 2001-02, his idea was to develop a small-scale, cost effective impedance osmometer suitable for in-clinic use on a commercial scale. The patent refers to a need for a “clinically feasible nanolitre scale osmolarity measurement”. It took approximately ten years of research and development and millions of dollars of investment to eventually achieve a clinically feasible system.
[40] Dr. Sullivan explained that the ‘540 Patent’s statement regarding an existing in vivo method of measuring osmolarity directly on the ocular surface, refers to the Ogasawara Paper and its description of a pair of electrodes placed directly underneath the eyelid of a patient. He stated that placing electrodes on a flexible substrate, without compensating for the geometry of the tear fluid being measured, would cause osmolarity measurements to suffer from lack of precision. He explained that the current TearLab System extracts a sample of fluid from the eye using capillary action, once it is brought into contact with the eye, and deposits the sample on a microchip having a substrate and sample region such that that electrical energy imparted to the tear fluid produces an output signal that is used to provide an osmolarity reading.
[41] Dr. Sullivan was also asked about an OcuSense marketing document from 2003, which was co-authored by him and Mr. Eric Donsky. That document referred to OcuSense’s unique “lab on a chip” technology, including a chip, sample region, leads, a base unit, and the collection and placement of sample fluid. It mentioned that a nanolitre of tear will evaporate in just a few seconds. It also contained inaccurate statements, despite being directed at investors. For example, it described “electrodes that are hundreds of times smaller than the sharpest sewing needle”, as well as the “critical feature” of a neural network and ability to dynamically monitor sample behaviour, neither of which was ever implemented.
[42] Dr. Sullivan commented on the York Patent. He referred to it as a “foolish” patent, because there was no way of restricting circuit paths; however, he agreed that there would be current flow inside conjunctival tissue as well as tear film on the surface of the eyeball.
[43] Dr. Sullivan discussed the clinical trials that occurred in 2004. The trial log referred to the extraction of tears by a doctor using a capillary tube, the doctor delivering the sample to him in a different room, him depositing the sample fluid onto the substrate of a chip, the sample fluid bridging the electrodes on the chip and the production of an osmolarity reading. He admitted there was a problem with fluid sucking back into the capillary tube when it was being deposited on a chip. He also admitted the size of the electrode area was suboptimal. Furthermore, at that time he did not appreciate the depth to which temperature affected impedance. An improvement patent was filed was filed in 2006 as US Patent No. 7,111,502, which made narrow claims covering software addressing corruptive signals that were present during the clinical trials.
[44] Finally, Dr. Sullivan discussed a TearLab marketing document from 2010, which he designed when he was the company’s Chief Scientific Officer. It was designed to look like a scientific journal article and handed out at conference attended by ophthalmologists and optometrists, who may have purchased the device after TearLab obtained regulatory approval. Dr. Sullivan referred to this as a “white paper” and said this practice was not uncommon.
[45] While there is no question that Dr. Sullivan was a credible witness concerning the development of the ‘540 Patent’s invention, his credibility was weakened by his admissions of making inaccurate and exaggerated claims in his marketing publications.
V. Plaintiffs’ Expert Witnesses
A. Dr. James Wolffsohn
[46] Dr. James Wolffsohn (“Dr. Wolffsohn”) is the Associate Pro Vice Chancellor of the School of Life and Health Sciences and a Professor of Optometry at Aston University in Birmingham, UK, as well as adjunct professor at the University of Houston, College of Optometry. He obtained a Ph.D. in optometry and vision sciences in 1997 and received a clinical post-graduate diploma in advanced clinical optometry in 1999. He was also a committee member on the 2017 Tear Film and Ocular Surface Society (“TFOS”) Dry Eye Workshop (“DEWS”), a global workshop concerning aspects of DED, and co-author of a seminal DEWS report. Dr. Wolffshon has extensive clinical practice with DED patients.
[47] Dr. Wolffshon is an expert in the physiology of the eye, clinical optometry and eye care and ophthalmic instrumentation. He is also an expert in the field of DED.
[48] Dr. Wolffsohn outlined the chronological development of the understanding of osmolarity as a biomarker for DED. Osmolarity was understood as a potential biomarker in 1995; however, it was not used in clinical practice. In his opinion, the situation remained the same in 2002. Freezing-point depression analyzers (the Clifton osmometer, the Fiske 110 osmometer and the Osmomat 030) were the primary technology for measuring tear osmolarity but were expensive, difficult to operate and only a few research facilities could access that technology. A trilogy of articles was published in the mid-1990s by Mitsubayashi and Ogasawra that discussed the use of electrodes to measure the conductance of tear film, which resulted in osmolarity measurement, but that technology was not developed to the point of commercialization. Those articles were not cited until 2006, but were published in a reputable journal. Other known methods of diagnosing DED in 2002 included tear staining, Rose Bengal staining and Schirmer’s test (to measure tear volume).
[49] On cross-examination, Dr. Wolffsohn was asked about his connections with TearLab. He is named in an international patent application that refers to a paper coauthored by him and Dr. Sullivan, among others, which mentioned that he received support from TearLab; TearLab provided their product for use in the research. As well, Dr. Wolffsohn is the principal investigator in an ongoing study in which TearLab set up clinical sites but did not provide funding. Furthermore, Dr. Sullivan was part of a committee that Dr. Wolffsohn was chairing, and he has worked on reports with both Dr. Sullivan and Dr. Sullivan’s father, Dr. David Sullivan, who is the founder and chairman of the board of directors of TFOS; Dr. David Sullivan’s wife and daughter are also involved with TFOS.
[50] Dr. Wolffsohn was shown an inconsistency between two of his reports. In his validity report, he referred to TearLab’s osmolarity technology as the gold standard for DED diagnosis in 2007. However, he wrote in a 2017 journal publication, “[n]o single ‘gold standard’ sign or symptom that correlates perfectly with the DED state has been established.” He explained that the statement in his validity report does not refer to the element of correlation between symptoms and DED, which he was discussing in the 2017 journal publication.
[51] While Dr. Wolffsohn was generally credible, his testimony did little to help deal with claim construction or the validity and infringement issues before the court.
B. Dr. Brian Kirby
[52] Dr. Brian Kirby (“Dr. Kirby”) is a Professor at the Sibley School of Mechanical and Aerospace Engineering at Cornell University in Ithaca, New York, and Professor of Engineering and Medicine in the Department of Medicine, Division of Hematology/Oncology at Weill-Cornell Medicine College in New York, New York.
[53] He is an expert in electrical and medical engineering, bioengineering and analytical chemistry. He is also an expert in the field of microfluidics, which involves the development of micro-technology, including microchips, to manipulate and analyze small quantities of fluids, including DNA and other biological materials. Microfluidics is not well-defined. It could involve devices having fluids in micron-sized channels. It could also involve the placement of a fluid on the outer portion of a microchip.
[54] Dr. Kirby submitted two expert reports and provided testimony on issues directly related to infringement and validity of the ‘540 Patent. Portions of his submissions are provided throughout these reasons where they are relevant to the Court’s analysis.
VI. Defendant’s Fact Witnesses
A. Mr. Daniel Hofmann
[55] Mr. Daniel Hofmann (“Mr. Hofmann”) is currently the President of I-MED. He has a Bachelor of Science in biochemistry and a certificate in human resources from McGill University, and a Master in Business Administration from the University of Montreal.
[56] Mr. Hofmann stated that I-MED was incorporated in Quebec in 1989. It has 20 full-time employees and one consultant. It was started by Mr. Hofmann’s father, Dr. Ilan Hofmann. Generally speaking, I-MED sells medical equipment to eyecare professionals around the world, in both human and veterinary fields.
[57] Mr. Hofmann discussed I-MED’s awareness of different methods of diagnosing DED prior to the i-Pen. Eyecare professionals relied on patient questionnaires, staining tests, volume tests (Schirmer’s test) and osmolarity tests. Those tests had a low correlation to DED and were time consuming and expensive.
[58] Mr. Hofmann explained how the i-Pen was developed. Mr. Zvi Nachum (“Mr. Nachum”) was introduced to I-MED in 2011. Mr. Nachum had a company called Life Care Ltd. and a prototype that consisted of a metal box, two leads, and an electrode attached to each lead, which he claimed could measure moisture in ocular tissue. Mr. Nachum used this device to measure moisture in the mouth, but was not an eye expert. In 2011 to 2012, I-MED guided Mr. Nachum and invested in his further research. Mr. Nachum eventually developed the prototype into a device similar to the current i-Pen. I-MED did extensive testing on the device to confirm its functionality. The i-Pen’s appearance was improved and a microchip was added to the SUS that contains a serial number, which the i-Pen stores to prevent a second use of that SUS. A patent application for the device was filed in 2012 by Mr. Nachum, but I-MED had no involvement with the patent filing or prosecution.
[59] Mr. Hofmann then demonstrated use of the i-Pen in accordance with the user manual, with counsel for I-MED acting as a patient. The patient closes their eyes for 30-60 seconds. Upon opening, the technician inverts the lower eyelid to expose the palpebral conjunctiva, approaches with the i-Pen at a 30-45 degree angle, allows the electrodes on the SUS to have good contact with the conjunctiva for up to four seconds, and then a resulting osmolarity reading is given.
[60] Mr. Hofmann explained that Life Care Ltd. manufactures the i-Pen and SUS in Israel. I-MED orders them from Life Care Ltd. and imports them into and sells them in Canada. Life Care Ltd. subcontracts the manufacturing of the i-Pen to a company named Medimor Ltd.
[61] On cross-examination, Mr. Hofmann stated there had been no change in the concept of the i-Pen since 2011, but some changes to the algorithm (the source code in the i-Pen software) were made between prototype 1 and 2, and then prototypes 2 and 3. The first commercially launched version was version 6 and the algorithm in the commercial device has never been changed.
[62] Mr. Hofmann believed that I-MED had never done experiments using the i-Pen on dry tissue. As well, his understanding is that all experiments using a solution only were done with an adaptor. His father did experiments involving solutions on dry wipes; he assumed this was done with a commercial i-Pen and adaptor but was not sure. He agreed that Mr. Nachum had done experiments that involved swabbing the lower eyelid and spraying it with a known solution, for the purpose of determining the accuracy of the i-Pen.
[63] Mr. Hofmann explained that the lower tear meniscus is located at the junction between the cornea and the conjunctive tissue, and a well of tear fluid sits in that junction. The i-Pen is not placed on the lower tear meniscus but it is placed on the palpebral conjunctiva.
[64] Mr. Hofmann stated that Dr. Richard Maharaj is a consultant of I-MED and sits on their medical advisory board. He has done post-market surveillance studies on the i-Pen. As well, Dr. Maharaj has worked for a publication sponsored by I-MED. I-MED provides a grant and topics they want discussed in the publication, but the publication decides which doctors to contact, which questions to ask, writes the draft and has final say on the editing. In one paper, Dr. Maharaj refers to the SUS as a “chip”.
[65] Mr. Hofmann admitted on cross-examination that a scale in the i-Pen user manual was similar to a scale in the TearLab Utility Guide. The scale helps eye care professionals compare osmolarity readings to severity of DED. The two scales are nearly identical, but the i-Pen scale has a slightly broader range.
[66] Mr. Hofmann agreed his father had sent him an email regarding experiments in 2015 that produced differing results between the i-Pen and the TearLab System. It was important to correlate readings of the devices because they would likely be compared in the market. The email stated, “[t]here is a difference and we can solve this difference by one of two means.” The two options were to change the algorithm in the i-Pen or to shift the scales. In the end, I-MED created its own ranges. Mr. Hofmann thought it was theoretically possible to adjust the algorithm in the i-Pen to create a new calibration curve, but he did not know details of software programming and did not think this had been done.
[67] Mr. Hofmann explained that clarifications to the i-Pen user manual were brought to his attention due to this litigation but were not made for the purpose of the litigation. The January 2016 user manual states, “…a tear fluid collection and testing device for the quantitative measurement of osmolarity (concentration of dissolved, active particles in solution) of human tears.” The March 2016 version states, “…a device for the quantitative measurement of osmolarity concentration of dissolved active particles in tissue immersed in solution of human tears…” As well, a change was made from “…provide a direct assessment of the osmolarity of the tissues surrounding the eye…” to “…provide an assessment of osmolarity of the conjunctival tissues surrounding the eye.”
[68] Mr. Hofmann agreed none of the previous user manuals contained the phrase “conjunctival tissue”, although each manual mentions the device touching the inner eyelid. As well, there was no significance difference between “tissues surrounding the eye” and “conjunctival tissues surrounding the eye”. Furthermore, “active particles in solution” referred to solutes that conduct electricity, specifically in the extracellular fluid of the conjunctival tissue, and it was not necessary to add “tissue immersed in solution” because it meant the same thing.
[69] Mr. Hofmann referred to an April 2007 email from his father to Mr. Nachum correcting a test report that erroneously said the i-Pen collected nanolitre quantities of tears. However, Mr. Hofmann admitted that a 2012 draft protocol for an i-Pen clinical study stated that the impedance that will be measured is the impedance of tears.
[70] Mr. Hofmann was a credible witness.
B. Mr. Zvi Nachum
[71] Mr. Nachum is from Israel. He spent five years in engineering s