Case 1:18-cv-01363-CFC Document 86 Filed 03/22/19 Page 1 of 100 PageID #:
`11201
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`C.A. No. 18-924-CFC
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`GENENTECH, INC. and CITY OF HOPE, )
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`Plaintiffs and Counterclaim Defendants,
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`AMGEN INC.,
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`Defendant and Counterclaim Plaintiff.
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`GENENTECH, INC. and CITY OF HOPE, )
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`Plaintiffs and Counterclaim Defendants,
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`SAMSUNG BIOEPIS CO., LTD,
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`Defendant and Counterclaim Plaintiff.
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`C.A. No. 18-1363-CFC
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`[SECOND CORRECTED]
`DECLARATION OF JOHN A. GLASPY, M.D., M.P.H.
`IN SUPPORT OF DEFENDANTS’
`CLAIM CONSTRUCTION BRIEF
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`Case 1:18-cv-01363-CFC Document 86 Filed 03/22/19 Page 2 of 100 PageID #:
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`Table of Contents
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`Page
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`I.
`II.
`III.
`IV.
`V.
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`Background and Qualifications .......................................................................................... 1 
`Nature of Assignment and Materials Considered .............................................................. 3 
`Person of Ordinary Skill in the Art .................................................................................... 4 
`Legal Standards for Claim Construction............................................................................ 5 
`Technical Background ....................................................................................................... 7 
`A.
`Introduction to Drug Dosing .................................................................................. 7 
`B.
`Dosage Regimens for Trastuzumab ..................................................................... 10 
`Claim Construction of “An Initial Dose” ......................................................................... 12 
`VI.
`VII. Amgen’s Construction Is Supported by the Specification and Prosecution Record
`of the Dosing Patents ....................................................................................................... 13 
`A.
`The meaning of “initial dose” is “first dose” ....................................................... 13 
`B.
`The specification equates “initial dose” with “first dose” ................................... 14 
`C.
`The patent describes two distinct treatment regimens ......................................... 15 
`D.
`The claim term “an initial dose” in the asserted claims covers only one of
`the treatment regimens ......................................................................................... 17 
`VIII. Genentech’s Construction is Incorrect ............................................................................. 17 
`IX.
`Summary of My Opinions ............................................................................................... 19 
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`-i-
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`I, Dr. John Glaspy, declare as follows:
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`I.
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`Background and Qualifications
`1.
`I have more than 35 years of experience in the fields of hematology and
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`medical oncology. I received a Bachelor of Science in Biology from University of
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`Santa Clara in 1975. I received my M.D. from University of California, Los Angeles
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`(“UCLA”) School of Medicine in 1979, as well as my M.P.H. from UCLA School
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`of Public Health in 1979.
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`2.
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`I completed my internship and residency in Internal Medicine at the
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`UCLA Center for Health Sciences in 1980 and 1982, respectively. I completed a
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`fellowship in Hematology-Oncology at the UCLA in 1985. I am board certified in
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`Internal Medicine, Medical Oncology, and Hematology.
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`3.
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`I am currently employed by the David Geffen School of Medicine at
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`UCLA as the Associate Chief in the Division of Hematology-Oncology, a position I
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`have held for almost 30 years. I have also been a Professor of Medicine at the David
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`Geffen School of Medicine for nearly 20 years. In addition, I am the Vice-Chair of
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`the Jonsson Comprehensive Cancer Center (“JCCC”) Scientific Protocol Review
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`Committee, and I hold the Estelle, Abe, and Marjorie Sanders Endowed Chair in
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`Cancer Research of the JCCC at the UCLA School of Medicine. During my career
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`at UCLA, I have also held the positions of Director of the Solid Tumor Unit, Director
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`1
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`of the Bowyer Oncology Center, Associate Director of the Medical Oncology
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`Program Area at the JCCC, Dean for Clinical Affairs, Director of the JCCC Clinical
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`Research Unit, Chair of the JCCC Safety Monitoring Board, and Director of the
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`JCCC Women’s Cancer Research Program.
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`4.
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`I have been a practicing clinician since I graduated medical school. My
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`clinical oncology practice focuses primarily upon treating patients with breast cancer
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`melanoma. Approximately 65% of my practice at UCLA is treating breast cancer.
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`5.
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`I am very familiar with the monoclonal antibody called trastuzumab
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`that is used to treat cancers that present with tumors overexpressing the HER2
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`protein, such as HER2+ breast cancers. I first gained experience treating patients
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`with trastuzumab during my participation in clinical trials for Herceptin, dating back
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`to 1995.
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`6. When appropriate for a specific patient, I have prescribed trastuzumab
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`since it was approved in 1998 and up to present day. I would roughly estimate that
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`I have prescribed trastuzumab to more than two thousand patients. In my current
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`practice, I would estimate that I treat roughly 40% of new breast cancer patients with
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`trastuzumab.
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`2
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`I have authored and co-authored more than 173 peer-reviewed research
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`7.
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`papers, and over 220 abstracts. I was recognized on the list of “Best Doctors in
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`America” from 1995-2009, and again in 2013.
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`8.
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` Additional details of my background are set forth in my curriculum
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`vitae, attached as Exhibit A to this Declaration, which provides a more complete
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`description of my educational background and work experience. I am being
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`compensated for the time I have spent on this matter at the rate of $400 per hour.
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`My compensation does not depend in any way upon the outcome of this proceeding.
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`I hold no interest in any party to this action.
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`II. Nature of Assignment and Materials Considered
`9.
`I have been asked by counsel for Amgen to opine regarding the
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`construction of the claim term “an initial dose” as recited in certain asserted claims
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`of U.S. Patent Nos. 6,627,196 (the “’196 patent”), 7,371,379 (the “’379 patent”), and
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`10,160,811 (the “’811 patent”) (collectively, the “Dosing Patents”).1
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`1 I understand that Genentech is asserting specific dependent claims against Amgen:
`Claims 11 and 22 of the ʼ196 Patent, Claims 11 and 21 of the ʼ379 Patent, and Claims
`6 and 7 of the ʼ811 Patent. I understand that these dependent claims incorporate the
`terms of the parent independent claims that they refer back to, which is where the
`term “an initial dose” is first recited. Accordingly, I reference those independent
`claims in this declaration and generally refer to the group of claims as the “asserted
`claims.” An appendix of the asserted claims, and the parent claims they reference,
`is provided at the end of this declaration.
`3
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`In forming my opinions, I have relied on my knowledge, education,
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`10.
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`skills, experience, and training, in addition to the documents and materials cited in
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`this declaration. Counsel for Amgen have provided me with certain legal standards
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`that are germane to my opinions. Those legal standards are set forth in this
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`declaration, and I have applied them in considering the issues and forming the
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`opinions I express in this declaration.
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`11.
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`I have reviewed the Dosing Patents and the references and materials
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`cited in the text of my declaration. I have also reviewed the prosecution histories
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`(the record of the Patent Examiner’s statements and arguments, and the inventors’
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`arguments and responses) of the Dosing Patents. I have also reviewed the portion
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`of Genentech Inc.’s Opening Claim Construction Brief regarding the Dosing Patents.
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`III. Person of Ordinary Skill in the Art
`12.
`I understand that claim terms are interpreted from the perspective of a
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`person of ordinary skill in the art (“POSA”) at the time of the invention. I understand
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`that a POSA is a hypothetical person who is presumed to have known the relevant
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`art at the time of the invention. I have been asked to assume that the relevant time
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`of invention is August 27, 1999, which is the filing date of the earliest application
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`listed on the first page of the Dosing Patents (provisional application No.
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`60/151,018). In analyzing the interpretation of the claims and teachings of the
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`4
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`written record, and in preparing the opinions set forth in this declaration, I have
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`applied the POSA perspective as of the time of the invention.
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`13.
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` I have been informed that the following factors may be considered in
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`determining the level of ordinary skill: (A) type of problems encountered in the art;
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`(B) prior art solutions to those problems; (C) rapidity with which innovations are
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`made; (D) sophistication of the technology; and (E) educational level of active
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`workers in the field.
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`14.
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`In my opinion, a POSA for the Dosing Patents would have knowledge
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`and experience regarding at least oncology and/or in oncology drug development.
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`Such an individual would also have familiarity with the treatment of breast cancer
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`and experience in the design and/or implementation of oncology clinical trials, as
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`well as expertise in clinical pharmacology, including pharmacokinetics and
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`experience in working in consultation with a pharmacokinetic specialist.
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`IV. Legal Standards for Claim Construction
`15. Below I set forth the instructions I have been provided by counsel
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`regarding legal standards for claim construction to apply in connection with
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`preparing my opinion.
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`16.
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`I am informed that claim construction is the process of interpreting
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`certain terms in the patent claims. Patent claims define the scope of the patented
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`5
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`invention, and they must be definite in that they must particularly point out and
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`distinctly claim the invention. I understand that a claim is definite if its scope can
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`be ascertained by a person of skill in the art with reasonable certainty, and that a
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`claim can be invalid for being “indefinite” if it does not comply with this
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`requirement.
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`17.
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`I am informed that words in a claim are generally given their ordinary
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`and customary meaning to a POSA, in view of the context of the claim language in
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`which the term appears, other claims, the specification and figures of the patent, and
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`the prosecution history. I understand that these sources are collectively called the
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`“intrinsic” evidence and that claim terms must be interpreted in light of the
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`“intrinsic” record because a POSA would read the term in the context of that
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`evidence.
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`18.
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`I am also informed that a patentee may define a term in the specification
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`and act as a lexicographer. I am informed by counsel that to act as a lexicographer,
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`the patentee must clearly set forth a definition of the term that is different from its
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`plain and ordinary meaning, doing so in a manner that expresses a clear intent to
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`redefine the term.
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`19.
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`I am informed by counsel that the prosecution history, as part of the
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`“intrinsic” record as noted above, can be informative for understanding the meaning
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`6
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`of a claim term. I am informed that if the patentee makes clear and unambiguous
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`disavowals of claim scope during prosecution, that a claim term should be
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`interpreted to exclude the disclaimed or disavowed scope.
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`20.
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`I am informed by counsel that “extrinsic evidence” refers to evidence
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`outside of the intrinsic evidence, such as expert testimony, scientific articles and
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`dictionary definitions. I am informed that extrinsic evidence can also be considered
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`and may be useful in understanding the meaning of claim terms to one of ordinary
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`skill in the art at the time of the invention.
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`V. Technical Background
`A.
`Introduction to Drug Dosing
`21. The Dosing Patents do not contain a detailed background discussion of
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`drug dosing. The description in the following paragraphs is a basic introduction to
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`the pertinent concepts in the field, as they would have been understood by a person
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`of ordinary skill in the art at the time. In support of this discussion, I provide
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`background based on my own experience. I also refer to disclosures in the
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`pharmacology textbook Rowland, et al., Clinical Pharmacokinetics: Concepts and
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`7
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`Applications, Lippincott Williams & Wilkins (3rd ed. 1995) (Ex. 42 (Rowland &
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`Tozer 1995)). Rowland & Tozer’s text is recognized as a preeminent volume in this
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`field. I note that the text was cited during the prosecution of the ʼ811 patent. (Ex. 2
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`(Nov. 13, 2013 IDS) at 14.)
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`22. A dosage regimen is defined as “the manner in which a drug is taken.”
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`See Ex. 4 (Rowland & Tozer 1995) at 1. The choice of a given dosage regimen
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`depends on the therapeutic objectives for the patient, which may be to cure, mitigate,
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`or prevent disease. Id. These desired objectives inform the amount of drug taken,
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`how often the drug is taken, and the duration of treatment. Id.
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`23. Optimal drug administration often requires knowledge of the kinetics
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`of drug absorption, distribution, and elimination. See Ex. 4 (Rowland & Tozer 1995)
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`at 2. These measurements describe a drug’s pharmacokinetic profile. Id. When
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`pharmacokinetic principles are applied to the therapeutic management of patients,
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`this is called clinical pharmacokinetics. Id.
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`24.
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`It is a basic tenet of clinical pharmacokinetics that the magnitude of
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`response and toxicity of a drug are functions of the concentration of the drug at the
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`2 All exhibits (“Ex. #”) cited herein are Exhibits to the Declaration of Michelle S.
`Rhyu, as described in the Exhibit List at the end of this declaration, unless otherwise
`noted.
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`8
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`site of action. See Ex. 4 (Rowland & Tozer 1995) at 1. Physicians generally use the
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`blood plasma to indirectly measure the concentration of drug at the site of action.
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`See id. at 3. An optimal concentration of drug is high enough to achieve effective
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`therapy, yet low enough to avoid unacceptable toxicity. Id. The therapeutic
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`objective is achieved by maintaining this optimal concentration in the body for the
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`duration of treatment. See id. at 1-2.
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`25. A common approach to the maintenance of continuous drug therapy is
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`to give multiple, discrete doses of a drug throughout the duration of treatment. See
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`Ex. 4 (Rowland & Tozer 1995) at 80. This is known as a multiple-dose regimen.
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`See id. The principle behind multiple-dose regimens is the phenomenon of drug
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`accumulation. When the amount of drug administered during the first dosing
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`interval has not completely dissipated before administration of the second dosing
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`interval, the concentration of drug in the body accumulates until a plateau is reached.
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`See id. at 84. This occurs when a drug is administered at a constant rate such that
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`the rate of elimination is equal to the rate of infusion. Id. Reaching this plateau, or
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`constant concentration, is also known as reaching “steady state.” See id. at 85.
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`26. For many drugs, the therapeutic objective is recognized through a
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`multiple-dose regimen using a high initial dose, followed by smaller maintenance
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`doses. Ex. 4 (Rowland & Tozer 1995) at 3. This approach is commonly used to
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`shorten how long it takes to achieve steady state in the patient by beginning the
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`therapy with a larger dose than will be used during the duration of the treatment.
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`Under this regimen, the patient is administered an initial dose that is designed to
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`quickly reach the optimal plasma concentration. Thereafter, smaller subsequent
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`doses are administered at discrete time intervals in order to maintain concentration
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`within the therapeutic range. Ex. 4 (Rowland & Tozer 1995) at 3; see
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`JA00000011(4:21-26; 4:61-65).
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`27.
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`It is important to consider patient comfort and convenience when
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`designing dosage regimens. For example, the duration of treatment may be driven
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`by the drug’s side effects, toxicity, and the economics of administration. Ex. 4
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`(Rowland & Tozer 1995) at 1.
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` Treating physicians must balance the
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`pharmacokinetic aspects of drug dosing with the recognition that continuous or too-
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`frequent drug administration can cause undesirable side effects, risk exposing the
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`patient to toxic substances, and multiply the expense associated with the treatment.
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`B. Dosage Regimens for Trastuzumab
`28. The design of dosage regimens using trastuzumab for the treatment of
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`breast cancer followed the familiar multiple-dose approach described above.
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`Herceptin®, Genentech’s brand name for trastuzumab, was first approved by the
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`U.S. Food and Drug Administration (“FDA”) in September 1998. Ex. 1 (Herceptin
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`10
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`1998 Label). Upon approval, Herceptin® was released with a drug label that
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`specified the following dosage regimen: “The recommended initial loading dose is
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`4 mg/kg Trastuzumab…[t]he recommended weekly maintenance dose is 2 mg/kg.”
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`See Ex. 1 (Herceptin 1998 Label) at 2. The Dosing Patents also describe this same
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`regimen and describe it as “recommended.” (JA00000011( 3:61-65).) By 1998, this
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`dosage regimen of using a high initial loading dose followed by subsequent
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`maintenance doses for the treatment of breast cancer was well known and
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`documented in the field of breast cancer oncology, and had been employed during
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`the pre-approval clinical development of trastuzumab. See JA00000733-40 (Baselga
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`1996) at JA00000734 (“Each patient received a loading dose of 250 mg of rhuMAb
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`HER2 on day 0, and beginning on day 7, 100 mg weekly for a totally of 10 doses.”);
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`see also JA00000741-53 (Pegram 1998) at JA00000741). This dosage regimen
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`remains on the current Herceptin® drug label. Ex. 3 (Herceptin 2018 Label).
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`29. The Dosing Patents describe further multiple-dose treatment regimens
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`wherein the patient is administered an initial dose designed to quickly reach the
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`optimal plasma concentration, followed by smaller subsequent doses to maintain that
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`concentration.
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`11
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`VI.
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` Claim Construction of “An Initial Dose”
`30. The claim term “an initial dose” is recited in the asserted claims of the
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`Dosing Patents, including: claim 1 of the ’196 patent, claim 1 of the ’379 patent, and
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`claims 1 and 7 of the ’811 patent.3 Claim 1 from the ’196 patent reads as follows,
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`with the claim language at issue underlined:
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`1. A method for the treatment of a human patient diagnosed with cancer
`characterized by overexpression of ErbB2 receptor, comprising
`administering an effective amount of an anti-ErbB2 antibody to the
`human patient, the method comprising:
`administering to the patient an initial dose of at least approximately 5
`mg/kg of the anti-ErbB2 antibody; and
`administering to the patient a plurality of subsequent doses of the
`antibody in an amount that is approximately the same or less than the
`initial dose, wherein the subsequent doses are separated in time from
`each other by at least two weeks.
`JA00000037-38(Claim 1).
`31.
`I understand that Amgen has proposed that “an initial dose” should be
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`construed by the Court to mean “the first dose of the claimed antibody given to the
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`patient as part of a treatment regimen.”
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`32.
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`I understand that Genentech has proposed that “an initial dose” should
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`be construed to mean “initial single dose or initial series of doses.”
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`3 See footnote 2 above.
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`12
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`VII. Amgen’s Construction Is Supported by the Specification and
`Prosecution Record of the Dosing Patents
`A. The meaning of “initial dose” is “first dose”
`33. Based on my experience treating patients with trastuzumab in the mid
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`to late 1990s, in my opinion the ordinary meaning of “an initial dose” as used in the
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`patents is a single first dose given to a patient as the beginning part of a treatment
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`regimen. I note that a preeminent textbook on pharmacology discussed above also
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`equates initial dose with “first dose.” See Ex. 4 (Rowland & Tozer 1995) at 88. An
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`initial dose is recognized as a distinct dose within a regimen because a patient who
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`has never before been treated will not have any of the drug in their body.
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`Accordingly, as I discussed above, it is common to given an initial higher dose to
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`“load” the patient with the drug, so as to more quickly achieve a metabolic steady-
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`state where the average concentration of the drug is in the therapeutic range.
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`34. Second, the 1998 Herceptin label, which I understand to be “intrinsic”
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`evidence to the Dosing Patents, confirms Amgen’s construction. The Herceptin label
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`describes the first 4 mg/kg dose as “the initial loading dose.” (Ex. 1 (Herceptin 1998
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`Label); see also (JA00000011(3:61-65).) Based on the plain and ordinary meaning
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`of “initial loading dose,” as described above, a POSA would understand this to mean
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`the single first dose administered to the patient. I note that the current Herceptin
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`13
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`label maintains this “initial dose” language in describing all four of the currently
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`approved treatment regimens. (Ex. 3 (Herceptin 2018 Label).)
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`35.
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`I also note that the common dictionary definition of “initial” in the
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`relevant timeframe was “[h]appening…or being at the very beginning: first.” (See
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`Ex. 5 (Webster’s New College Dictionary) at 570.) In the mid to late 1990s and
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`today, this definition applied equally in this field, such that “initial dose” means “first
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`dose.”
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`B.
`36.
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`The specification equates “initial dose” with “first dose”
`In my opinion, the fact that the specification uses the terms “initial
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`dose” and “first dose” synonymously confirms the terms mean the same thing in the
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`context of this field. For example, in describing the purported invention, the
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`specification states: “[T]he invention provides a method for the treatment of cancer
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`… comprising administering to the patient a first dose of an anti-ErbB2 antibody
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`followed by at least one subsequent dose of the antibody…” (JA00000012(6:22-
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`26).) In a later discussion, the patent uses “initial dose” in place of “first dose:” “the
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`invention provides a method for the treatment of cancer in a human patient …
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`comprising administering to the patient an initial dose of at least approximately 5
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`mg/kg of the anti-ErbB antibody; and administering to the patient a plurality of
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`14
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`subsequent doses of the antibody…” (JA00000012(6:54-60).) A POSA would
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`understand the patent’s use of “an initial dose” to mean the “first dose.”
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`C. The patent describes two distinct treatment regimens
`37. The specification describes two distinct dosage regimens: one wherein
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`“an initial dose” is a single, first dose administered to the patient; and another
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`wherein there is a series of initial doses. For example, the specification summarizes
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`the invention by stating “[t]he present invention concerns the discovery that an early
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`attainment of an efficacious target trough serum concentration by providing an initial
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`dose or doses of anti-ErbB2 antibodies followed by subsequent doses of equal or
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`smaller amounts of antibody (greater front loading) is more efficacious than
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`conventional treatments.” (JA00000011(4:21-26).) The specification goes on to
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`describe an alternative dosage regimen involving multiple initial doses: “As an
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`alternative regimen, initial doses of 4 mg/kg anti-ErbB2 antibody may be
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`administered on each of days 1, 2 and 3, followed by subsequent maintenance doses
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`of 6 mg/kg once per 3 weeks.” (JA00000026(34:27-31).)
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`38.
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`In my opinion, a person of ordinary skill in the art would interpret these
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`teachings to disclose that the inventors viewed “an initial dose” as a distinct and
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`alternative dosing regimen to the use of “initial doses.” One of skill in the art would
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`read the patent as teaching that these regimens are two different and alternative ways
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`to dose the anti-ErbB2 antibodies discussed in the specification. This is based not
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`only on the discussion in the specification itself, but also on how these terms are
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`applied in the field as I explain below.
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`39. The alternative dosage regimens described in the specification align
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`with two distinct multiple-dose regimens prescribed in clinical practice. As
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`described in Section V.A., certain dosage regimens are designed such that a higher
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`initial dose is administered in order to achieve the optimal concentration of drug in
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`the body more rapidly. See Section V.A., supra. This single, higher first dose is
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`followed by subsequent doses that maintain the optimal concentration of drug in the
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`body for the duration of treatment. A POSA would understand “an initial dose” to
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`encompass this particular dosage regimen.
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`40. However, in other, less common, circumstances, a patient may be
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`unable to receive a higher initial dose as a single administration, for instance due to
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`toxicity concerns. In that case, a POSA would prescribe an alternative dosing
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`regimen, wherein the higher initial administration is broken down into several
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`smaller administrations given in close succession to allow the drug to accumulate in
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`the body and eventually reach the optimal concentration for therapy but with less
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`concern about toxicity. The specification describes such a dosing regimen: “In
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`another method, the front loading initial dose is a series of intravenous or
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`subcutaneous injections, for example, one on each of days 1, 2, and 3 of at least 1
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`mg/kg for each injection (where the amount of anti-ErbB2 antibody delivered by the
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`sum of initial injections is more than 4 mg/kg), followed by maintenance doses of 6
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`mg/kg once each 3 week interval to maintain a target trough serum concentration
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`(for example, approximately 10-20 μg/ml) of HERCEPTIN® anti-ErbB2 antibody.”
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`(JA00000031(44:57-65).) This alternative regimen would be described as an initial
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`series of doses, and would encompass the second, alternative dosing regimen
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`discussed in the patent wherein a patient is given a plurality of initial doses.
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`D. The claim term “an initial dose” in the asserted claims covers only
`one of the treatment regimens
`41. A POSA would understand the term “an initial dose” in the asserted
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`claims (for example JA00000037-38(Claim 1)) refers only to the first treatment
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`regimen described above, where “an initial dose” is a single first dose.
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`42.
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`In contrast, a different claim, independent Claim 16, recites “wherein
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`the initial dose is a plurality of doses.” This claim captures the alternative regimen
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`of a series of initial doses, such as the example I provided above in paragraphs 37-
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`40.
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`VIII. Genentech’s Construction is Incorrect
`43. As discussed above, a POSA would not understand “an initial dose” to
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`include a “series of doses,” and therefore Genentech’s construction is incorrect. The
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`patent describes two alternative dosage regimens: one wherein “an initial dose” is a
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`single, first dose administered to the patient; and another wherein there are multiple
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`initial doses. Genentech’s construction encompasses the second treatment regimen.
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`See Section VIII.B., supra.
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`44. Genentech contends that the specification “defines” “an initial dose” to
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`include a series of doses. However, when reading the specification, a POSA would
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`not have understood the inventors to have clearly set forth a definition for “an initial
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`dose” that is different from its plain and ordinary meaning of a single, first dose.
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`There is no language in the specification that redefines this common term. Instead,
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`as discussed above, a POSA would understand the specification as clearly describing
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`two alternative dosage regimens.
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`45. Furthermore, in my opinion Genentech’s construction would make the
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`asserted claims ambiguous. A POSA would not understand with reasonable certainty
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`the scope of claim 1 under Genentech’s construction. I note that all the asserted
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`claims recite both an initial dose and a plurality of subsequent doses. Under
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`Amgen’s construction, it is simple to differentiate between those two kinds of doses
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`when examining a dosage regimen – the initial dose is the first dose and the
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`subsequent doses are doses that come after. But if “an initial dose” were to be
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`defined according to Genentech’s construction as a “series of doses,” a POSA
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`reading the claims of the Dosing Patents would not be able to distinguish between
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`the initial doses and subsequent doses of a treatment method. For example, Baselga
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`described a dosage regimen for trastuzumab wherein each patient received 10 doses
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`– a “loading dose” of 250 mg, followed by 9, 100 mg doses given weekly. See
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`JA00000734 (Baselga 1996). Under Genentech’s construction, it becomes
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`ambiguous whether that regimen has one initial dose and nine subsequent doses, or
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`ten initial doses and no subsequent doses, or any number in between. A POSA
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`would not understand where the initial doses end and where the subsequent doses
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`begin. By contrast, with Amgen’s construction, “an initial dose” means the single
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`first dose, and later doses are “subsequent doses.” Accordingly, in my opinion the
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`asserted claims would be indefinite if the Court were to apply Genentech’s proposed
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`construction.
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`IX. Summary of My Opinions
`46. Amgen’s proposed construction of “an initial dose” as “the first dose of
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`the claimed antibody given to the patient as part of a treatment regimen,” is in
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`accordance with how a POSA would interpret the term after reviewing the claims
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`and the written record of the patents. A POSA would not understand “an initial dose”
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`in the asserted claims to include a “series of doses,” and therefore Genentech’s
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`construction is incorrect.
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`I declare under penalty of perjury that the foregoing is true and correct.
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`47.
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`Dated (as corrected): February 25, 2019
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`Dr. John Glaspy
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`CORRECTED APPENDIX OF ASSERTED CLAIMS OF THE DOSING PATENTS
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`Claim(s) Claim Language
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`6,627,196 (Baug