IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In the Inter Partes Reviews of:
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`U.S. Patent No. 6,676,609
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`Trial Number: IPR2014-00639
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`U.S. Patent No. 7,004,913
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`Trial Number: IPR2014-00641
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`U.S. Patent No. 6,258,044
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`Trial Number: IPR2014-00642
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`DECLARATION OF FRANK FROMOWITZ
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`Patent Owners CDx /SMR -Exh.
`2001
`U.S. Endoscopy Group v. CDx
`Diagnostics Inc. and Shared
`Medical Resources, LLC
`IPR2014-00642
`
`
`
`In the Inter Partes Reviews of:
`
`U.S. Patent No. 6,676,609
`
`Trial Number: IPR2014-00639
`
`U.S. Patent No. 7,004,913
`
`Trial Number: IPR2014-00641
`
`U.S. Patent No. 6,258,044
`
`Trial Number: IPR2014-00642
`
`DECLARATION OF FRANK FROMOWITZ
`
`Patent Owners CDx /SMR -Exh.
`2001
`U.S. Endoscopy Group v. CDx
`Diagnostics Inc. and Shared
`Medical Resources, LLC
`IPR2014-00642
`
`
`
`
`
`I, Frank Fromowitz, MD, declare and provide expert testimony as follows:
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`INTRODUCTION
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`1. My name is Dr. Frank Fromowitz. I have been employed by CDx
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`Diagnostics (hereinafter CDx), since April, 2012, serving as Assistant
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`Medical Director for the last year.
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`2. I submit this declaration as an expert in this inter partes review. I make the
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`statements below of my own personal knowledge and, if called as a witness,
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`would testify to the following.
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`3. I am a licensed physician and I practice as an anatomical pathologist in New
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`York State.
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`4. I have approximately 35 years of experience in diagnostic pathology. My
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`background details and professional experience are detailed in the
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`curriculum vitae attached hereto as Exhibit 2002.
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`5. Currently, at CDx I review specimens obtained by CDx’s brush biopsy
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`instruments.
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`6. I have provided expert testimony in several professional/malpractice cases
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`over the last several years but do not recall the details of the cases, but can
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`supplement this, if needed.
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`7. Although I am not being compensated for my time spent apart from my
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`regular salary, the following opinion is based on my knowledge of
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`anatomical pathology and tissue collection that I learned over the course of
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`35 years as a pathologist starting in 1978.
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`8. All of the opinions I express in this report are opinions that I hold to a
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`reasonable scientific certainty. By that I mean that my opinions are
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`consistent with scientific principles that are generally accepted within the
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`academic and scientific communities in the field of pathology and that I do
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`not hold any significant doubts about the accuracy of my opinions.
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`9. I expect that I may be asked to testify about my opinions regarding the
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`Asserted Patents as well as general matters regarding technology and science
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`relevant to these patents.
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`10. In forming the opinions expressed in this declaration, I have reviewed U.S.
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`Patent Nos. 6,258,044; 6,676,609; 7,004,913 (the Asserted Patents). I have
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`reviewed several dictionaries and attach selected portions therefrom relating
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`to the terms tissue and biopsy. I also reviewed the Declaration of Dr. Michel
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`Kahaleh (Exhibit 1011) and attended the deposition of Dr. Kahaleh taken on
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`December 8, 2014. I have also relied to a large extent upon my own
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`experience and expertise in the relevant fields. This declaration provides the
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`CDx EXHIBIT 2001
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`basis for any testimony that I expect I may be asked to give on behalf of the
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`patent owners in this matter.
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`BACKGROUND
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`11. Anatomical pathology is a medical specialty that relates to the diagnosis of
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`disease based on review of organs, tissues and/or cells collected from the
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`human body. Anatomic pathology practitioners are generally separated into
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`two categories based on the type of specimens they are respectively trained
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`to analyze – namely, histopathologists and cytopathologists. Histopathology
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`refers to the art of analyzing tissue for diagnosis of disease, whereas,
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`cytopathology refers to the art of analyzing cells for diagnosis of disease.
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`When histopathologists review whole tissue, they largely analyze the overall
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`tissue architecture – with less emphasis on the morphological appearance of
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`individual cells. Cytopathologists, on the other hand, review individual cells
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`that are removed from their natural tissue architecture, and as such, there is
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`typically no tissue architecture to analyze. Cytopathologists, therefore,
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`analyze individual cells in order to learn about the health of their tissue of
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`origin.
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`12. Histologic preparations are usually obtained using an instrument such as a
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`scalpel, biopsy forceps or punch biopsy device, which extracts whole tissue
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`CDx EXHIBIT 2001
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`from a patient. Such biopsies typically obtain surface tissue, underlying
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`submucosa and muscle tissue. At the laboratory, the tissue is cut into several
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`“slices” using a microtome. The slices are very thin, substantially flat sheets
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`of tissue showing the intact architecture of the tissue.
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`13. Historically, and as of 1998, cytology samples were typically obtained using
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`a relatively soft cytology brush to pick up loose exfoliated cells or surface
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`epithelial cells from a tissue of interest. Cytology brushes are specifically
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`designed to obtain surface cells without causing trauma to the tissue being
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`sampled. Cells obtained with a cytology brush are then transferred onto a
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`glass slide and presented to a cytopathologist as a monolayer of cells for
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`examination.
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`14. As described above, both types of anatomic pathologists are trained to
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`review specimens that are substantially flat. Flat preparations are
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`conventionally used in order to eliminate overlapping objects and to avoid
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`the need for a reviewer to constantly adjust the viewing lens of a
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`microscope. The specimens obtained with CDx brushes, on other hand, are
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`rather thick and difficult to analyze by routine microscopy.
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`15. A brush to obtain a full-thickness tissue biopsy invariably destroys the
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`tissue architecture and yields a disaggregated tissue specimen. The specimen
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`retrieved is different from that obtained with a forceps biopsy and while
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`CDx EXHIBIT 2001
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`each may obtain some of the same cells, they will each not obtain all the
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`same cells due to the differences in obtaining specimens with a brush or a
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`forceps biopsy.
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`16. In my 35 years as a practicing pathologist, I have never seen or analyzed a
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`thick disaggregated full-thickness tissue specimen as described above until I
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`began working for CDx.
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`DEFINITION OF THE WORD “BIOPSY”
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`17. I reviewed the expert declaration of Dr. Michel Kahaleh, and I disagree with
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`some of the statements and conclusions contained therein.
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`18. Dr. Kahaleh stated that “In my experience, a biopsy is an examination where
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`a doctor takes a sample of living tissue…from a patient in order for it be
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`examined to determine the health of the tissue.” This aspect of the definition
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`is consistent with my own understanding of the word “biopsy” and is in
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`agreement with the consensus of the medical community as evidenced by the
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`medical dictionary definitions attached hereto. For example, Dorland’s
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`(Exhibit 2003) defines “biopsy” as “the removal and examination, usually
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`microscopic, of tissue from the living body, performed to establish precise
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`diagnosis.” Stedman’s (Exhibit 2004) defines a “biopsy” as the “Process of
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`CDx EXHIBIT 2001
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`removing tissue from living patients for diagnostic examination. 2. A
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`specimen obtained by [biopsy].”
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`19. As set forth above, a “biopsy,” in essence, refers to the removal of “tissue”
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`for diagnostic purposes. “Tissue” is defined as “an aggregation of similarly
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`specialized cells united in the performance of a particular function” (See
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`Dorland’s, Exhibit 2003), or as “A collection of similar cells and the
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`intercellular substances surrounding them…” (See Stedman’s Exhibit 2004).
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`“Tissue,” in essence, is any group of similar cells – so that an intact
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`superficial layer of epithelium is considered tissue. The definition of “tissue”
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`does not refer to layers of tissue or include a minimum number of layers.
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`20. The term “biopsy,” thus, is a general term used to describe collecting tissue
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`from a body site. There are several types of biopsies all of which fall under
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`the rubric of “biopsy.” Common examples of “biopsies” include
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`“endometrial aspiration biopsy” where a tissue sample of the lining of the
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`uterus is taken; “shave biopsy” where a superficial layer of skin is scraped;
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`“excisional biopsy,” where an entire lesion is removed for analysis; and
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`“incisional biopsy” where a part of lesion is removed. (See Exhibits 2003
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`and 2004)
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`21. Dr. Kahaleh’s statement that “when a biopsy is performed a doctor
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`understands and expects that epithelial tissue will be at least part of the
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`CDx EXHIBIT 2001
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`biopsy sample and that the biopsy sample will include not only fragments of
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`epithelial tissue but also fragments of submucosa” is incorrect. Different
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`sampling techniques yield different specimen samples, and the suggestion
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`that all biopsies contain epithelial tissue and fragments of submucosa is
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`incorrect and unsupported. A “biopsy” does not inherently include epithelial
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`tissue and fragments of submucosa. In fact, to the contrary, there are various
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`epithelial cell preparations in which a pathologist would expect not to find
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`submucosa fragments. For example, purposely superficial biopsies (for
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`example, superficial shave biopsy of skin) typically contain only superficial
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`tissue without any presence of submucosa.
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`22. In view of the above, a biopsy is simply the removal of tissue – without
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`reference to layers. In addition, not all biopsies contain more than one layer
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`of epithelium – let alone basal layers or layers below the basal layer. Any
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`suggestion that the term “biopsy” necessarily includes more than one tissue
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`layer is contrary to established medical consensus as set forth above.
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`23. It is my opinion that one of ordinary skill in the field of biopsies is an
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`anatomical pathologist with at least two years hospital or laboratory practice
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`after completion of training.
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`24. I further note that Dr. Kahaleh is a gastroenterologist doctor.
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`Gastroenterologist doctors may be skilled in that art of performing
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`CDx EXHIBIT 2001
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`endoscopy procedures including performing tissue biopsies; however, Dr.
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`Kahaleh is not skilled in the art of analyzing biopsy specimens, diagnosing
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`disease based on review of biopsy specimens, and making determinations as
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`to the sufficiency and/or adequacy of biopsy specimens.
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`25.A pathologist, on the other hand, is specifically trained to diagnose disease
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`based on biopsy samples and to determine the adequacy/sufficiency of such
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`samples. As a practicing pathologist, I am one of ordinary skill in the art of
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`reviewing biopsy samples including determining what constitutes a biopsy,
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`and what type of respective biological samples are expected to be obtained
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`where biopsies are performed using different sampling instruments and
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`techniques.
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`In 1998, I was a Professor of Pathology and Laboratory
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`Medicine at the University of Medicine & Dentistry of New Jersey.
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`I also
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`had approximately 20 years of experience as a pathologist.
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`I declare under penalty of perjury that the foregoing is true and correct.
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`Dated: December l‘6,20l4
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`/4lfl,{(gl,:i
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`Dr. Frank Fromowitz
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`8
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`CDX EXHIBIT 2001
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