Goldfarb v. Wl Gore & Associates Inc.

Goldfarb v. Wl Gore & Associates Inc.
Court (s) Database
Federal Court Decisions
Date
2001-02-09
Neutral citation
2001 FCT 45
File numbers
T-2567-87
Notes
Digest
Decision Content
Date: 20010209
Docket: T-2567-87
Citation: 2001 FCT 45
BETWEEN:
DAVID GOLDFARB
Plaintiff/
Defendant by Counterclaim
- and -
W.L. GORE & ASSOCIATES, INC.
Defendant/
Plaintiff by Counterclaim
REASONS FOR JUDGMENT
LEMIEUX J.:
INTRODUCTION AND BACKGROUND
[1] The sole question to be decided in this subsection 43(8) Patent Act proceeding (the "Act"), now repealed, is who, as between Dr. David Goldfarb and Peter Cooper, having assigned his invention rights to his employer, W.L. Gore & Associates Inc. ("Gore"), is the first inventor of the appropriate internal structure for an artificial vascular prosthesis for implantation in the human body to replace natural veins and arteries. The material used in the fabrication of this prosthesis is expanded porous polytetrafluoroethylene ("ePTFE") with the internal microstructure consisting of nodes interconnected by fibrils. This microstructure, and in particular, the distance between the nodes (in other words, the fibril length) is said to be the invention because it permits and controls tissue cellular ingrowth and assures the establishment and health of a thin viable neointima, consisting of endothelial cells, necessary for smooth blood flow.
(a) Dr. Goldfarb's patent application in Canada
[2] Dr. Goldfarb filed his patent application in Canada on January 16, 1975. Gore followed by filing in Canada on March 19, 1975, both claiming priority dates from U.S. filings.
[3] Dr. Goldfarb, in his application, wrote that a principal aspect of his invention was to provide a vascular prosthesis capable of replacing or bypassing veins and arteries having relatively small diameters as well as those vessels of intermediate and larger pore. He identified the prior art grafts which were machine-woven from tightly twisted dacron or teflon fibres.
[4] Dr. Goldfarb identified the problems surgeons encountered with such grafts and spelled out the benefits of the structure derived from ePTFE, that is, a homogeneously porous vascular prosthesis with small nodes interconnected with extremely fine fibril and characterized (a) by an average internodal distance (i) large enough to allow the migration of typical red cells and fibroblasts and (ii) small enough to inhibit both excessive blood flows at normal pressure and excessive tissue ingrowth; and (b) an average of wall thickness which is (i) small enough to provide proper mechanical conformity to adjacent cardiovascular structures (suturing) and (ii) large enough to prevent blood clotting and excessive tissue ingrowth.
[5] Dr. Goldfarb noted the methods and techniques to expand PTFE have been known for many years and ePTFE has been used, without clinically meaningful or reproducible success, for artificial vessel replacement quoting Soyer et al. in Surgery, "A New Venus Prosthetic", vol. 72, page 864, December 19, 1972, and Matsumoto et al. in Surgery, "A New Vascular Prosthesis for Small Caliber Artery", vol. 74, October 19, 1973.
(b) Mr. Cooper's Canadian filing
[6] Mr. Cooper, in his March 19, 1975 patent filing, abstracted his application in the following terms:
This invention provides an artificial vascular prosthesis suitable for implantation to replace damaged, defective or occluded veins or arteries. The prosthesis comprises of a tube of expanded porous, polytetrafluoroethylene possessing a microstructure consisting of nodes interconnected by fibrils. The suitable range of fibril length for such a prosthesis is 5-1000 microns, with the preferred range being 20-100 microns.
[7] Mr. Cooper described the prior art in terms similar to what Dr. Goldfarb had said in his patent application. He also described experimentation on grafts constructed of synthetic textile materials and said none had been entirely successful. He said for total success, an artificial arterial prosthesis must provide an open pathway for blood to pass along its entire length and additionally must not generate embolization to the distal arterial bed.
[8] Mr. Cooper, referred to certain experiments implanting a vascular prosthesis made with ePTFE in animals. He provided four examples, showing the preferred range of fibril length at about 20-100 microns.
[9] In his first example, Mr. Cooper said two series of experiments were conducted using dogs for the animal model and using the two carotid arteries and two femoral arteries for the segmental replacement site. In both experimental series all grafts were expanded porous ePTFE tubes with variations in length (4 cm) in diameter (4 mm) as well as the wall thickness (20-32 mils), the density of the material (0.25-0.34 g/cc) and the fibril length (5-1000 microns).
[10] The first series involved 64 implantations of which 36 grafts had been harvested, the remaining being in living animals with palpable pulses over the grafts. He said this experiment yielded an expected patency rate of 87.5% for the entire series. He said histological examination of the patent grafts demonstrated fibroblastic ingrowth, capillary formation and the development of uniform, smooth neointima throughout the lengths of the graft as well as over the suture line.
[11] Mr. Cooper described the second series of experiments involving the implementation of 107 grafts of which 51 had been harvested. Out of those harvested, a patency rate of 76.4% resulted. In these two series all grafts with a fibril length ranging from 5 to 20 microns yielded a 100% patency rate.
[12] In his second example, Mr. Cooper describes that 32 grafts constructed from ePTFE were substituted in one carotid artery in each of 32 sheep. Of the grafts harvested, he indicated they were all patent. The fibril lengths were 3 to 150 microns.
[13] In his third example, he wrote that grafts of ePTFE were interposed in the carotid and femoral arteries and femoral vein of mongrel dogs and that 36 grafts had been implanted of which 18 had been harvested, all of them patent. The fibril length ranged from 25 to 1000 microns.
[14] In his fourth example, he described experiments involving 12 grafts interposed in the abdominal aortas of twelve dogs of which five had been harvested and all of them patent. The fibril lengths were 20 to 40 microns.
(c) The conflict proceeding and the Commissioner's decision
[15] After receiving these two applications, the Commissioner of Patents (the "Commissioner") declared conflicting claims and defined the subject matter in conflict by drafting eight claims. The Commissioner then received, under then, but now repealed, subsection 43(5) of the Act, sealed affidavit evidence and on June 11, 1987, awarded four conflict claims to Dr. Goldfarb and four conflict claims to Gore.
[16] The Commissioner awarded conflict claims C-1 to C-4 to Gore on the basis that the date of invention was on May 19, 1973, when Mr. Cooper exhibited, during an Open House at Gore's Flagstaff plant in Arizona, photomicrografts of slides evidencing tissue ingrowth in artificial veins implanted in dogs, as contrasted to an invention date of January 16, 1975, the date when Dr. Goldfarb filed his Canadian application.
[17] The Commissioner awarded claims C-5 to C-8 to Dr. Goldfard based on an invention date of mid-July 1973 as the result of his experiment known as the 64-graft series as contrasted to a date of February 1974 for Mr. Cooper. February 1974 is when Mr. Cooper received a report by Mr. Detton, Research Coordinator at Gore in Flagstaff Arizona. This was a progress report on the research being conducted by various medical researchers on ePTFE grafts over the previous six months.
THE FACTS
(a) Prior experimentation on ePTFE before the Goldfarb/Gore linkage
[18] Before he joined the Arizona Heart Institute ("AHI") in January of 1973, Dr. Goldfarb, during the 1960s, had conducted research on artificial vascular grafts for human applications at John Hopkins University and at the University of Pittsburgh. These grafts were made of woven or synthetic materials and typically were for the replacement of large veins since they had a minimum internal diameter of 8 to 10 mm; attempts at implanting smaller artificial grafts had been unsuccessful.
[19] Mr. Cooper joined Gore in the early 1960s starting as a machine operator and then becoming a shift supervisor. In 1964-1965 he opened a sales office in California for Gore and after his return, he designed at Gore PTFE coated products for the wire and cable industry. In 1967, he was transferred to Flagstaff, Arizona, as plant manager to a new plant established for the production of PTFE coated wire and cable products.
[20] In May of 1970, Robert Gore filed a patent application for ePTFE including the methods for making ePTFE tubing. Gore and Mr. Cooper wanted to develop uses for ePTFE tubing. One of those uses was for medical applications. In the Fall of 1970, Gore equipped its Flagstaff plant with a tubing extruder to make ePTFE tubing.
[21] Mr. Cooper's first medical research contact was in December 1970 with Dr. Ben Eiseman, a surgeon at the University of Colorado in Denver, who implanted an ePTFE Gore tube in a dog's vena cava in January 1971. Dr. Eiseman and doctors associated with him (Drs. Norton, Soyer and Kelly) began conducting experiments during the summer and late fall 1971, implanting ePTFE vein grafts in experimental animals (dogs and pigs). By November 11, 1971, Dr. Eiseman's group had done 31 animal experiments using ePTFE tubes supplied by Gore. None of those tubes clotted and there were patencies of three months which Dr. Eiseman reported as being "very exciting".
[22] In December 1971, Dr. Eiseman's group performed an implant of a Gore-made ePTFE graft, 9mm in diameter, in the portal vein of a human. This was said to be the first implant of any prosthetic portal vein of any material in a human. The operation was successful and the patient was discharged.
[23] As a result of these developments, Dr. Eiseman and his team prepared a paper for presentation, on June 22-23, 1972, at the Society of Vascular Surgery. Mr. Cooper reviewed a draft summary (an abstract) of this paper and made corrections in the description of the characteristic of the Gore tubes. Mr. Cooper is named as one of the authors of the paper.
[24] Throughout the latter part of 1972, Gore, through Mr. Cooper and Mr. Richard Mendenhall, another Gore employee, expanded their medical research contacts and forwarded to them sample grafts of ePTFE tubing for research purposes using a new numbering system to keep track of the tubing by lot number. Among the medical researchers contacted by Gore were Dr. Lawrence H. Cohn of Peter Bent Brigham Hospital in Boston and a team of doctors at the University of Utah, Drs. Jarvik, Knolff and Volder.
[25] On August 15 and 21, 1972, Mr. Cooper summarized the work being done at various medical centers on Gore ePTFE made grafts (hereinafter known as "GORE-TEX grafts") in two reports to its president Bill Gore. In his August 21, 1972 report, Mr. Cooper indicated that he now thought tissue ingrowth was a good thing.
[26] On September 11, 1972, Mr. Cooper contacted Dr. Sharp in Akron, Ohio, and described to him the structure of ePTFE as a matrix of nodules interconnected by fibrils with open pore spaces between the fibrils. On that same date, he wrote to other medical researchers giving them similar information.
[27] As noted, throughout the fall of 1972, medical research continued on the GORE-TEX grafts. As well, refinements were made to the production process at Gore for the making of such grafts or tubes and as well how best to identify its internal structure because tubes that are identical in density and dimension can have different internal structures. Measurement at Gore of internal structure of its manufactured grafts is now made by way of an ethanol or alcohol bubble point measurement ("EBP").
[28] On October 31, 1972, Mr. Cooper sets up an experiment with three different manufacturing processes to identify variations in the Gore grafts' internal structure. These manufacturing processes are by: (1) slow hand expansion, (2) very fast gun expansion and, (3) a modified standard expansion. On November 2, 1972, Gore, with the participation of one of its employees Harold Green who joined Gore in the fall of 1971 as an engineer responsible for manufacturing ePTFE tubing, launched an experiment known as the "Three-Structure Experiment". The tubes made by the slow hand expansion were called within Gore as "poker chipped" tubes. These grafts have low EBP (large pores) whereas the gun-produced grafts have high EBP (small pores) and were manufactured at Gore between November 2nd and 8th, 1972 before Dr. Goldfarb began his experiment on GORE-TEX tubing.
[29] On November 10, 1972 , Mr. Cooper sent grafts made of GORE-TEX tubing of the three variants in the Three-Structures Experiment to Drs. Eiseman, Volder, Sharp and Kerth and stated that Gore had established a relationship with an electron microscope company to look at the internal structures of the tubes.
[30] In December 1972 and, as noted by Dr. Goldfarb in his Canadian patent application, Dr. Soyer's article was published in Surgery and Mr. Cooper was named as one of its authors. The ability of a GORE-TEX made vascular graft was disclosed. What was not know was why it would remain patent.
[31] In January of 1973, both Drs. Volder and Cohn reported successful implants in various types of animals in the context of the Three-Structures Experiment.
(b) The link between Dr. Goldfarb and Gore
(1) February 1973
[32] After determining Dr. Goldfarb would consider using ePTFE Gore tubing in his research, Richard Mendenhall from Gore on February 2, 1973, sent Dr. Goldfarb samples of ePTFE tubing which Gore had previously fabricated for the "Three Structure Experiment" and several reprints regarding the use of GORE-TEX as a vascular prosthesis and as an oxygenator. Mr. Mendenhall wrote to Dr. Goldfard "we feel that this material might prove useful as a synthetic coronary artery bypass graft".
[33] After receiving this material from Gore, Dr. Goldfarb testified he cut thin slices of the sample tubing and examined it under a 100 power optical microscope. Dr. Goldfarb said he knew from the prior teachings of Dr. Wesolowsky as well as from his own past experience that a successful graft requires tissue ingrowth in order for the blood to be exposed to the natural tissue which forms in and around the graft. He also said he knew, to achieve tissue ingrowth, the graft must have open pore spaces into which fibroblast (average 5 microns) can enter and, in addition, the thickness of the wall of the graft must permit cellular infiltration and be flexible and suturable.
[34] Dr. Goldfarb testified, after microscopically examining the Gore sample tubing, he saw, at that time, the ePTFE material consisted of nodes and fibrils with the nodes defining the open pore spaces which would permit desired tissue ingrowth. He testified he felt the ePTFE tubing would function successfully as a vascular prosthesis if the pores in the material could be altered so as to best accommodate the fibroblast for the purpose of healing the graft into the patient's tissue.
[35] He said, in his testimony, it became clear to him after examining ePTFE sample, the important parameter in terms of allowing cells to enter was the distance between the solid ePTFE nodes and he realized that the open distance between the nodes, "pore size" or "internodal distance", would have to be at least 5 microns, the approximate diameter of the disk-shape fibroblast in order that it may fit between the nodes. Based on his work with other graft materials, Dr. Goldfarb testified he knew the desired tissue ingrowth occurred between the solid portions of synthetic graft material, known as interstices and the tissue would ingrow between the solid ePTFE nodes.
[36] Dr. Goldfarb testified the fibrils which connected the nodes of ePTFE grafts appeared to him to be quite thin and flexible and capable of moving to allow cells to pass through by being pushed apart. He testified from his experience, a fibroblast is a highly mobile and motive cell capable of changing its shape to fit through a given pathway.
[37] Again, drawing from the teachings of Dr. Wesolowsky, Dr. Goldfarb testified he realized, after examining the Gore ePTFE sample before implant, the distance between the nodes should not be so large as to allow bleeding through the wall of the graft. He said he knew the distance between the solid ePTFE nodes should be smaller than the upper limit capable of preventing bleeding through the wall of the device. He testified the exact numerical value of the upper limit was not known, but could easily be determined by routine experimentation.
[38] On February 8, 1973, Mr. Cooper and Mr. Mendenhall visited Dr. Goldfarb at the AHI in Phoenix, Arizona. Dr. Goldfarb testified this was a substantial meeting where he explained to Gore's people the need for tissue ingrowth in order to make a graft successful and the key to graft success was its microstructure with a pore size (fibril lengths or internodal distances) of at least 5 microns so as to allow a fibroblast to pass through but not so large as to allow bleeding through the wall of the graft. On the other hand, Mr. Cooper testified this meeting was an introductory one and there was no discussion on the structure of the grafts or "pore size", or fibril lengths or internodal distance. Mr. Mendenhall did not testify in these Canadian proceedings as he had in the United States.
[39] On February 14, 1973, Mr. Cooper sent Dr. Goldfarb "a variety of sizes of GORE-TEX tubes for your animal artery prosthetic experiments". Dr. Goldfarb said he had this tubing cut into grafts for implantation after observing it under a microscope and mentally noting the internodal distance. However, he made no written recordings of this fact.
(2) Dr. Goldfarb's first series of experiments with Gore ePTFE
[40] On April 19, 1973, Mr. Cooper sent a letter to Dr. Goldfarb enclosing ePTFE tubing for experimentation which reads as follows:
The enclosed GORE-TEX tubes represent the latest attempt to achieve satisfactory patency rate in small artery prosthetics. We have penetrated the walls of the tubes with many (160-in) 50-100 micron holes to allow direct tissue growth through the tube walls. Hopefully these pathways will allow rapid, firm attachment of the neointema surface.
Up to date the research reports are enclosed. We will continue to provide new materials and experimental results as they become available. [emphasis mine]
[41] The up-to-date research reports included an abstract from a paper presented by Dr. Volder at the April 7-9, 1973 ASAIO meeting and a report by Dr. Sharp to Mr. Cooper dated April 2, 1973, which Dr. Goldfarb testified were not enclosed and later could not remember if they were enclosed in Mr. Cooper's April 19, 1973 letter.
[42] On April 25, 1973, Dr. Goldfarb began a first series of experiments using 21 ePTFE grafts implanted in seven dogs. Dr. Goldfarb testified before implanting the ePTFE tubing, he viewed the structure of the material under a microscope to insure that the internodal distances fell roughly within his desired range. Unfortunately, Dr. Goldfarb did not transcribe his pre-implant internal distance observations in his laboratory records.
[43] The implanted grafts were removed from the animals after 21 days and histological slides were prepared from grafts specimens and preserved in paraffin blocks. Autopsy forms were maintained by James Moore who had been Dr. Goldfarb's laboratory technician when he was at the University of Pittsburgh. Again, Dr. Goldfarb did not record in writing the post implant fibril length observations which he said he made visually.
[44] On May 23, 1973, Dr. Goldfarb harvested the right carotid graft implanted in dog 2-73. It was patent. Other grafts harvested from dog 2-73 also proved to be patent showing the requisite tissue ingrowth. Dr. Goldfarb testified the internodal distances for dog 2-73 and others were above 5 microns because, if it was otherwise, he would not have implanted them. Dr. Goldfarb said these grafts likely had between 20 and 30 microns in internodal distance. These post-harvest measurements, he said, confirmed his pre-implant measurements, but unfortunately, as noted, he did not record neither of them.
[45] Dr. Goldfarb testified that in May of 1973, Mr. Mendenhall visited him a second time. He testified he told Mr. Mendenhall what he felt were the appropriate specifications for a successful small artery artificial vascular graft. He said he told him the internodal distance of the material had to be between 5 and about 100 microns with a preferred internodal distance of 20 to 30 microns, and a wall thickness of .25-.75 mm as well as be compliant and flexible.
[46] Dr. Goldfarb testified in the spring of 1973, more likely in June of that year, he met with Mr. Dan Detton. Dr. Goldfarb testified he transcribed his specifications for successful grafts on a piece of paper which he gave to Mr. Detton in the restaurant where they met. Dr. Goldfarb testified shortly after giving that piece of paper to Mr. Detton, he received a call from Harold Green at Gore. Dr. Goldfarb testified during this telephone call he reiterated his specifications. Harold Green testified in these proceedings and confirmed Dr. Goldfarb's testimony as to Dr. Goldfarb's specifications in terms of internodal distance, wall thickness, length and internal diameter. Mr. Green said these specifications became known at Gore as the "Goldfard structure".
(3) What was happening at Gore in February-May 1973
[47] A few days after Dr. Goldfarb's meeting with Messrs. Cooper and Mendenhall, Mr. Cooper received, on February 12, 1973, a report from Dr. Sharp providing him with the test results of the "GORE-TEX graft". Dr. Sharp wrote:
As of this date, I can only give you a partial analysis. We used the 21-day patency period has being the maximum evaluation time. All the grafts have been inserted but some have not gone the full 21 days yet. The results so far are as follows: 1) 416-10312-4 grafts inserted, 2 patent at 21 days; (2) 423-11082-2: 2 patent at 16 days; (3) 423-11082 (.29): 2 patent at 16 days, 1 patent at 20 days , 1 clotted at 24 hours, and 2 are still patent at 4 days; (4) 423-11082 (.30): 2 are patent at 5 days; (5) 416-10312-2: all clotted in less than 10 days time.
Microscopic studies and gross studies of inside of the patent artery at 21 days demonstrate a rather thick inner fibroses capsule or neointima which is very poorly attached to the prosthetic material ... It is too early to form definite conclusion from this study, but I think it if fair to say that all of the samples that which have received did not demonstrate a high degree of performance in the small artery position. [emphasis mine]
[48] Mr. Cooper testified the grafts with lot number 416-3 were the "poker chipped" grafts with the lowest EBP measured in pound per square inch which corresponded to the largest pore size in the Three-Structure Experiment.
[49] On March 21, 1973, Dr. Kelly wrote to Mr. Cooper advising him he had an opportunity to review all of the microscopic slides on GORE-TEX vein grafts done during the past four months. He said although all of them were clotted, "there is one outstanding feature which is worthy of comment". He said all of the medium density GORE-TEX grafts (.48 grams per cc) were only sparsely permeated by adjacent cells from the intimal adventitial surface. He said all of the low density grafts (.27 grams per cc) were totally infiltrated by adjacent cells. He added "obviously the critical aperture lies somewhere between these two densities". He wrote it would be of great interest to the research team in Denver "to know what the actual microscopic pore size is in these two separations". He asked Mr. Copper to have one of his microscopist measure the minimum, maximum and mean pore size.
[50] On April 2, 1973, Dr. Sharp provided Mr. Cooper with a report on the final testing of four samples of GORE-TEX material. He attached microphotos. In particular, he reported on the group I (GORE lot 416-3 (.31g/cc) (the poker chip structure). He said there were a total of four grafts inserted in the dog's carotid artery and that two remained patent for 21 days and two clotted before 21 days in another animal. He said the low power microscopic views demonstrated excellent fibroblastic infiltration of the wall of the graft and a fairly thick, but well attached neointima. He discussed the results of the other groups. He observed that only in Group I was there neointimal attachment as well as fibroblastic ingrowth of tissues on capillaries through the interstices of the wall graft. He concluded Group I proved to be the most promising. He recommended that further studies be carried out with Groups I, II and III with a recommendation that the wall thickness should be thinner and at least 12 grafts of each group should be tested and porosity measured.
[51] On April 9-11, 1973, Dr. Volder presented a paper at the conference of the American Society of Artificial Internal Organs. He reported that high porosity GORE-TEX grafts implanted in the carotid arteries of sheep remained patent for up to six months with smooth neointimas.
[52] On April 17, 1973, Dr. Kelly forwarded to Mr. Cooper four histological slides from four grafts harvested from dogs after one month. Mr. Cooper testified that Dr. Kelly had mis-labelled the manufacturing lot numbers from which the histological slides came from. Mr. Cooper said he determined from the internal diameter, from the outside diameter and from the density measurements that one of the lots Dr. Kelly labelled "416-11172-10(?)" was really lot 423-11072-3 sent to Dr. Eiseman on November 21, 1972, along with lot 416-11172-10 in the context of the "Three Structure Experiment".
[53] On Easter Sunday, April 22, 1973, Mr. Cooper testified, during a private children's party and Easter egg hunt, he viewed Dr. Kelly's slides and discussed them with Dr. Davee, a Flagstaff internist, and with John Giovale, a Gore engineer. He testified he realized that cellular ingrowth can occur between the nodes and the fibrils are not a bar to cellular ingrowth.
[54] The next day, that is April 23, 1973, Mr. Cooper testified he took photographs of Dr. Kelly's slides and put a scale on the photograph of the slide from dog 1571's left femoral vein so that fibril length (internodal distance) could be measured from the scale. He testified he instructed Harold Green that additional photographs were to be taken. Copies of these photographs were distributed to researchers in late May 1973.
[55] On May 1 and May 2, 1973, Mr. Cooper recorded in his lab book (P-Ex 79) the results of his analysis of the photographs he made from the slides sent by Dr. Kelly. On May 1, 1973 he wrote:
I want to maximise the amount and rate of tissue ingrowth into GORE-TEX vascular prosthetics. Two qualities are necessary. (1) uniform "poker chip" structure and (2) a "minimum skin at both the OD and ID surfaces.
Tissue has invaded GORE-TEX where the nodes are approximately 10-30 microns thick with most separation between nodes about 50-100 microns (photo 1). Other structures having approximately 5-10 microns node dimensions and spaces from about 5-30 microns do not appear to allow ingrowth (photo 2). [emphasis mine]
Mr. Cooper noted that both photos were from slides of grafts from femoral veins in dogs in which grafts failed in terms of patency.
[56] On May 2, 1973, Mr. Cooper entered further information in his lab book about the manufacturing conditions and pictures of the ID and OD surfaces of the graft in dog 1571, as well as a comparison photograph from another of Dr. Kelly's slide of a graft using a gun-expanded (small pore size) lot.
[57] Mr. Cooper testified making a thin walled poker chipped tube (0.32-inch wall) with a different extruder on May 3 and 4, 1973. During the summer of 1973, the extruding equipment was upgraded so as to produce a tube with less skin.
[58] Dr. Cooper testified that on May 8, 1973, he and Mr. Giovale visited a pathologist in Flagstaff to review Dr. Kelly's slides or photographs made from them.
[59] On May 9-11, 1973, Mr. Detton started his work at Gore as liaison with researchers working with GORE-TEX ePTFE grafts. He visited Dr. Volder and others at the University of Utah and wrote in his trip report that Dr. Volder was experimenting to determine the most appropriate GORE-TEX structure (i.e. pore size, density, wall size, etc.) (D-tab 202).
[60] Mr. Cooper testified on May 17, 1973 he attempted to make a thin-walled tube from film with 50-micron internodal distance, by wrapping the film in layers around a mandrel, hoping to get a tube which would allow tissue ingrowth. It did not work.
[61] On May 19, 1973, Gore had an Open House at its Flagstaff plant to celebrate the completion of its plant expansion. Exhibits were posted for viewing by visitors. Mr. Cooper testified he had the idea of exhibiting "before and after" photographs using a photograph made from a slide by Dr. Kelly and showing tissue infiltration as the "after" photograph and a slide of a Gore prosthesis before implant as the "before" photograph. The "before" photograph had a scale used to read off fibril length (internodal distance). It is not from the actual lot sent to Dr. Kelly.
[62] On May 30, 1973, Mr. Detton visited Dr. Goldfarb in Phoenix and in his trip report says he provided Dr. Goldfarb with the findings from Drs. Sharp and Volder regarding tissue ingrowth in the largest pore size grafts. Mr. Detton records that Dr. Goldfard advised him that he had recently inserted approximately 16 to 20 GORE-TEX grafts in dogs and that one of the grafts implanted was patent at three and a half weeks. The other three were not harvested, i.e. were still in the dog and believed to be free of trombosis at four weeks. Mr. Detton wrote Dr. Goldfarb told him GORE-TEX would become a successful prosthesis once the proper surgical technique was developed and once suitable GORE-TEX structures had been identified.
[63] On June 1, 1973, Messrs. Cooper and Detton visited Dr. Kelly in Denver; Mr. Detton wrote a trip report of that meeting. It indicates he was showed photographs of tissue ingrowth into the poker chipped GORE-TEX grafts.
[64] On June 6, 1973, Mr. Detton visited Dr. Goldfard and Mr. Moore. He made a trip report. The initial meeting with Mr. Moore, as Mr. Detton wrote it, consisted of an explanation of the findings of recent research relating to fibroblastic cellular and capillary ingrowth in GORE-TEX made grafts. Another aspect of his conversation with Mr. Moore related to a discussion of GORE-TEX structural variations and their potential significance in developing a successful vascular prosthesis. His trip report records he showed Mr. Moore photographs of the slides made by Dr. Kelly. Later that day, Mr. Detton met with Dr. Goldfarb but his trip report does not reveal the details of the conversation he had with him.
[65] On June 8, 1973, the day after Dr. Goldfarb had successfully harvested his second graft, Mr. Cooper made a notebook entry about ways of overcoming manufacturing difficulties in making poker chipped grafts with thin walls and without skin. The focus of his observations are to improve tissue ingrowth and cellular migration.
[66] On June 13, 1973, the day of Dr. Goldfarb's third successful graft, Mr. Detton visited him, Mr. Moore and Dr. Dietrich at the AHI. He wrote up a trip report Mr. Detton said he explained to them, during surgery on a dog, the tissue and capillary ingrowth findings and Gore's current efforts to define structural differences and their relationship to ingrowth, neointima viability and patency. Mr. Detton was present that day when Dr. Goldfard harvested graft 459-04133-9 which had been selected by Mr. Cooper and sent to Dr. Goldfard on April 19, 1973. It was a fully perforated tube, with 160 needle-punctured perforations per square inch. A second dog was examined and all four grafts showed signs of clotting. They were made from Lots 448-12222-1 and 2.
[67] The record indicates that in late June 1973, Mr. Detton visited various researchers to explore the possibilities of GORE-TEX as an artificial vascular graft.
(4) Dr. Goldfarb's second series of implants using Gore ePTFE
[68] At the beginning of July 1973, Dr. Goldfarb was joined by Dr. Charles Campbell. Dr. Goldfarb testified that on July 11, 1973, he began his second series of implants at Arizona State University and that the purpose of conducting this series was to confirm his specifications and to narrow down the ideal structure.
[69] The first implant was on dog 10-73 and following that, Dr. Campbell, under Dr. Goldfarb's supervision, implanted the grafts in the animals in this series. Dr. Goldfarb testified, as he had done in the first series, he and/or Dr. Campbell would review the grafts in this second series microscopically before the implant and after harvest to insure that the GORE-TEX material possessed Dr. Goldfarb's specifications and he said they did. As with the first series, the harvested grafts in the second series were placed in paraffin.
[70] Mr. Detton recorded, in a trip report, a meeting with Drs. Goldfarb and Campbell on July 18, 1973, and he said one of the purposes of that meeting was to determine those GORE-TEX structures which had provided the most favourable results and to eliminate those which had proved to be unacceptable. His report records the discarding of certain grafts made in certain lots of ePTFE material, the small pore size grafts. Dr. Goldfarb, in his testimony, did not recall that meeting but said Mr. Detton would not have assisted in determining the favourable structure.
[71] On August 2, 1973, the first patent grafts in the second series were harvested by Drs. Goldfarb and Campbell. On August 6, 1973, the second set of patencies in the second series were harvested and the next day, on August 7, 1973, the third set of patencies in that series was similarly harvested and note of the internodal distances was made.
[72] In a trip report dated September 18, 1973, after visiting the Arizona Heart Institute, Mr. Detton recorded the results of a comprehensive review of the success and failure rates relative to various GORE-TEX structures in the second series directed by Dr. Goldfarb which he said "produced some rather interesting but inconclusive results" and was not surprised "as the initial series of grafts was designed to merely indicate structural likelihood for favourable grafts". He reported as follows:
The second series of grafts implemented during July included 10 grafts of which 7 remained patent beyond the 21-day test. These grafts ranged from 4.9 mm in internal diameter to 3.0 mm in internal diameter and produced a patency rate of 70%. The pore size would be approximated at 10 to 20 microns which would certainly allow for both fibroblastic tissue invasion as well as capillary invasion into the interstices of these grafts. These patency rates, considering the extreme difficulty of the dog as a test site are far from discouraging and will be followed with a second series of implants.
(5) Events before Dr. Goldfarb's 64-graft series
[73] On August 10, 1973, Alan Uebler, Gore's patent agent, contacted Mr. Cooper after Robert Gore had discussed with him the possibility of obtaining an additional patent on the use of poker chipped GORE-TEX tube as an artificial artery or vein. He wrote to Mr. Cooper this possibility existed "if we can establish its new, useful, and non-obvious characteristics over existing products". He asked him to gather his records.
[74] Mr. Cooper followed up on August 21, 1973, with a memo to Mr. Uebler to whom he sent a second memo that same day which reads:
First, we have large holes from ID to OD between the dense nodes. The nodes spacing is in the order of 50-100 microns using optical measuring techniques.
Second, the holes are bridged from OD to ID with a multitude of fibrils.
Now, here is the point. The fibrils contain the blood even at arterial pressures due to hydrophobic and probably filtering properties but are not an obstacle to tissue invasion! On the contrary, the fibrils may encourage rapid tissue ingrowth! [emphasis mine]
[75] On August 10, 1973, Mr. Detton recorded a trip visit to Drs. Kelly and Eiseman. Dr. Kelly reported he had completed graft placement with large pore (65 microns) size GORE-TEX in eight dogs and was enthusiastic about the potential for GORE-TEX as a small caliber arterial prosthesis.
[76] On August 23-24, 1973, Mr. Detton visited Dr. Volder in Salt Lake City. Dr. Volder produced the three latest GORE-TEX vascular prosthetic grafts harvested from sheep for Mr. Detton's observation. These grafts had been harvested the previous week. Each of the three tubes represented a different GORE-TEX structure. One graft was fully punctured low density; another was a poker chipped tube possessing semi-puncture through the OD skin and another was the 6A resin large pore size material. Mr. Denton reported that each of these three structures had been sent for histological examination and following these results Gore would be able to determine the most appropriate structure for use as a vascular prosthesis. Further research on long-term patency was required.
[77] On September 20, 1973, Mr. Cooper recorded in his lab book the development of a microscopic technique that allowed the examination under an optical microscope of GORE-TEX poker chipped structures "so that we can be more precise about subtle changes possible with process variables". This technique (keyed to lighting), as Mr. Cooper testified, enabled the sintered grafts to be photographed and the fibril lengths to be measured over large areas of the graft. Mr. Cooper then ordered the photography of remaining samples from previous shipments and the measurement of fibril lengths on them.
[78] On September 13, 1973, Mr. Detton recorded a trip visit with Mr. Mendenhall to Dr. Kelly. Dr. Kelly had previously reported six small caliber (3mm) large pore size GORE-TEX grafts were patent after ten weeks.
[79] On October 2, 1973, Dr. Detton records a visit he and Mr. Giovale had at the AHI in which he indicates "I was pleased to learn that the last series of five grafts (vascular prosthesis lot number 569-07163-1) a 4.3 mm large pore size produced an 80% patency during the initial 21-day period". He added "although this does not constitute a large series, nonetheless, it is considered an extremely favourable result as false positives are impossible to obtain within the realm of dog testing". He noted discussion of some specifics of the research format to be utilized in the second phase of tests. The research format would include utilisation of pure bred dogs.
[80] On October 9, 1973, Mr. Detton once again visited AHI. He wrote he reviewed 15 different GORE-TEX graft structures with Drs. Goldfarb and Campbell and wrote:
This review was a most meaningful to date as it was possible to illustrate the various structures through 60x microphotographs of the OD surface, ID surface and wall crosssections of each graft. During the review, it became quite obvious that appropriate histological and pathological results needed to be reviewed prior to selecting the two most appropriate grafts for inclusion in the second phase of AHI's GORE-TEX research.
He recorded that Dr. Campbell seemed to favour the utilization of smaller pore size grafts with approximate pore size in the range of 15 to 25 microns. He reported Dr. Goldfarb felt larger pore size grafts with a consistency and smaller pore structure at the ID surface was more likely to prove successful as a small caliber artificial prosthesis.
(5) The 64 graft ser