Date: 20200416  
Docket: T-741-18  
Citation: 2020 FC 522  
Ottawa, Ontario, April 16, 2020  
PRESENT: The Honourable Mr. Justice Southcott  
Defendants by Counterclaim  
Plaintiff by Counterclaim  
I. OVERVIEW.......................................................................................................................... 3  
II. BACKGROUND ................................................................................................................... 5  
III. THE ASSERTED CLAIMS................................................................................................. 9  
IV. ISSUES................................................................................................................................. 10  
V. FACT WITNESSES............................................................................................................ 11  
A. MR. THOMAS BOONE (AMGEN WITNESS).......................................................................... 12  
B. DR. KRISZTINA ZSEBO (AMGEN WITNESS) ........................................................................ 15  
C. DR. HSIENG LU (AMGEN WITNESS)................................................................................... 17  
D. MS. ANITA HAMMER (AMGEN WITNESS) .......................................................................... 22  
Page: 2  
E. MS. SHEILA AHMED (PFIZER WITNESS)............................................................................. 23  
F. DR. GORAN VALINGER (PFIZER WITNESS) ........................................................................ 23  
VI. EXPERT WITNESSES ...................................................................................................... 24  
A. DR. RICHARD VAN ETTEN (PFIZER EXPERT)...................................................................... 25  
B. DR. MARK HERMODSON (PFIZER EXPERT) ........................................................................ 33  
C. DR. STEVEN BOXER (PFIZER EXPERT) ............................................................................... 36  
D. DR. STANLEY MALOY (AMGEN EXPERT)........................................................................... 40  
E. DR. DAVID SPEICHER (AMGEN EXPERT)............................................................................ 48  
F. DR. JAMES GRIFFIN (AMGEN EXPERT)............................................................................... 53  
VII. ABUSE OF PROCESS ................................................................................................... 58  
VIII. JUDICIAL COMITY ..................................................................................................... 63  
IX. CLAIM CONSTRUCTION - THE SKILLED PERSON ............................................... 65  
X. CLAIM CONSTRUCTION - ANALYSIS........................................................................ 67  
XI. OBVIOUSNESS DATE OF INVENTION .................................................................... 70  
A. PRIORITY DATE FROM THE 959 APPLICATION .................................................................... 71  
XII. OBVIOUSNESS ANALYSIS...................................................................................... 98  
A. LEGAL PRINCIPLES............................................................................................................. 98  
B. THE SKILLED PERSON AND THEIR COMMON GENERAL KNOWLEDGE ................................ 99  
C. INVENTIVE CONCEPT ....................................................................................................... 103  
D. STATE OF THE ART........................................................................................................... 108  
G. CONCLUSION ON OBVIOUSNESS ....................................................................................... 165  
XIII. SECTION 53 - MATERIAL MISREPRESENTATION .......................................... 166  
XIV. INSUFFICIENCY......................................................................................................... 172  
XV. PRIOR USE................................................................................................................... 177  
XVI. COSTS ........................................................................................................................... 186  
Page: 3  
This decision relates to an action by the Plaintiffs, Amgen Inc. and Amgen Canada Inc.  
[collectively, Amgen], against Pfizer Canada ULC [Pfizer], and a related counterclaim by Pfizer.  
Amgen brings this action pursuant to section 6(1) of the Patented Medicines (Notice of  
Compliance) Regulations, SOR/93-133 [Regulations], after being served with a Notice of  
Allegation by Pfizer pursuant to section 5(3) of the Regulations.  
Amgen Inc. is the current owner of Canadian Patent No. 1,341,537 [the 537 Patent].  
Amgen Inc. has authorized Amgen Canada Inc. to list the 537 Patent on the Patent Register  
against Amgen’s biologic drug NEUPOGEN, which the latter markets, sells, and distributes in  
Canada. The drug substance in NEUPOGEN and disclosed in the 537 Patent is generically  
known as filgrastim. Pfizer has filed with the Minister of Health a New Drug Submission [NDS]  
for the issuance of a Notice of Compliance [NOC] for its filgrastim biosimilar NIVESTYM.  
Pfizer’s NDS refers to NEUPOGEN as a reference biologic drug for the purposes of regulatory  
Amgen’s claim in this action alleges the making, constructing, using, selling, offering for  
sale, importing or exporting of NIVESTYM in accordance with Pfizer’s NDS would infringe  
certain claims of the 537 Patent. Pfizer’s defence and counterclaim allege the 537 Patent is  
invalid and void, due to obviousness of the asserted claims, insufficiency of the 537 Patent’s  
disclosure, and alleged misrepresentations to the Canadian Intellectual Property Office [CIPO].  
Page: 4  
Pfizer also asserts that, even if the patent is valid, it is protected against allegations of  
infringement by the defence of prior use.  
Some of the evidence adduced at trial is subject to a Confidentiality Order dated  
December 11, 2019 [the Confidentiality Order], in order to protect commercially sensitive  
confidential information of the parties. A draft confidential decision was therefore sent to the  
parties on April 6, 2020 to allow them to propose any redactions required for the issuance of the  
public version of the decision. Amgen proposed redactions to protect a non-party’s private health  
information and to protect the dates and durations of certain steps in the invention process, which  
Amgen considers commercially sensitive information. Pfizer does not object to redaction of the  
private health information but does oppose the other redactions.  
In the course of exchanging written submissions on this issue, Pfizer pointed out that  
several of the proposed redactions relate to a date that is accessible to the public in the file  
history for the 537 Patent. Amgen agreed and withdrew its request that this date be redacted.  
With respect to the remaining proposed redactions, Pfizer disputes Amgen’s assertion that these  
dates could affect its patent rights in other jurisdictions. Pfizer submits that Amgen is motivated  
by strategic litigation considerations and not by confidentiality interests in commercially  
sensitive information. Amgen responds, inter alia, that wishing to protect information because of  
litigation considerations would not diminish the confidential nature of the information.  
I agree with Amgen’s position. It has consistently treated the information at issue as  
confidential, including obtaining the Confidentiality Order and redacting the information from  
Page: 5  
the publicly filed versions of its fact witness affidavits. While a party with which it is in litigation  
in another jurisdiction may be able to obtain this information though the discovery process, it  
will presumably then be protected by a version of the implied undertaking rule or by a protective  
agreement or order. As the proposed redactions will not affect the intelligibility of the decision, I  
am satisfied that the redactions appropriately balance the interests of protecting confidential  
information and the public interest in open and accessible court proceedings. As such, two  
versions of this decision, one public and the other confidential, will be issued simultaneously.  
For the reasons explained in detail below, I find that the claims of the 537 Patent asserted  
by Amgen are obvious and therefore invalid. I do not find the 537 Patent as a whole invalid due  
to misrepresentation or insufficiency. I also find that, if the claims asserted by Amgen had been  
valid, Pfizer would not have been protected by the defence of prior use.  
The Plaintiff, Amgen Inc., is a corporation incorporated and existing under the laws of  
the State of Delaware with its principal place of business in Thousand Oaks, California. Amgen  
Inc. is a biotechnology company and is the current owner of the 537 Patent. The Plaintiff,  
Amgen Canada Inc. [Amgen Canada], is a corporation incorporated and existing under the laws  
of the Province of Ontario and located in Mississauga, Ontario. Amgen Canada is also a  
biotechnology company and markets, sells and distributes various biologic drugs in Canada,  
including the filgrastim drug NEUPOGEN. Filgrastim is used to treat neutropenia (a disorder  
wherein the body cannot produce sufficient levels of white blood cells called neutrophils), which  
Page: 6  
can develop as a result of damage to the body’s hematopoietic system (the system responsible for  
production of blood cells).  
The Defendant, Pfizer, is a corporation incorporated under the laws of Canada and has its  
head office and principal place of business in Kirkland, Québec. Like Amgen Canada, Pfizer  
sells pharmaceutical products including biologic drugs in Canada.  
[10] The 537 Patent is entitled “Production of Pluripotent Granulocyte Colony-Stimulating  
Factor.” It issued on July 31, 2007 from Canadian Patent Application No. 516,737 [the 737  
Application], filed on August 25, 1986. The 537 Patent claims priority to US Patent Application  
No. 768,959 [the 959 Application], filed on August 23, 1985, and US Patent Application No  
835,548 [the 548 Application], filed on March 3, 1986. Only the 959 Application is relevant to  
this proceeding, for reasons outlined below. Because of the dates surrounding this patent, the  
governing legislation in this action is the Patent Act, RSC 1984, c P-4 as it read immediately  
before October 1, 1989 [the Old Act]. The 537 Patent will expire on July 31, 2024. Amgen  
describes the patent as relating to a hematopoietic growth factor, made using recombinant  
genetic technology.  
[11] By way of general scientific background relevant to this description, a hematopoietic  
growth factor is, in this case, a protein, which stimulates the growth of blood cells. A protein is  
composed of a string of amino acids. There are 20 different amino acids found in proteins of  
mammalian species. A recombinant protein is one produced in a laboratory through DNA  
technology. This involves, inter alia: (a) combining the DNA that codes for the target naturally  
Page: 7  
occurring protein with another piece of DNA, a process called cloning that forms recombinant  
DNA; (b) inserting that recombinant DNA into a host cell, referred to as transforming the cell;  
and (c) replicating the transformed host cell to form a colony of such cells, which express the  
target protein because of the presence of the protein’s DNA.  
[12] The 537 Patent refers to the target protein, i.e. the naturally occurring protein to be  
recombinantly produced, as “human pluripotent granulocyte colony-stimulating factor” or “hpG-  
CSF”. A colony-stimulating factor [CSF] is a hematopoietic growth factor that stimulates the  
growth of progenitor cells into colonies. Progenitor cells develop from stem cells and in turn  
form mature blood cells. There are different categories of progenitor cells, which in turn develop  
into particular categories of mature cells. Granulocytes (the G in hpG-CSF) are one category of  
mature white blood cell that matures from relevant progenitor cells. As noted above, the protein  
to which the 537 Patent relates stimulates colonies of neutrophils, which are a type of  
[13] The remaining term in the name the 537 Patent employs for the subject protein is  
pluripotent.The meaning of this term, particularly in the context of the 537 Patent’s  
disclosure, is controversial between the parties. As will be explained in greater detail later in  
these Reasons, the prior art describes the target protein as pluripotent, meaning in that context  
that it stimulated growth of multiple lineages of mature blood cells from progenitor cells.  
However, either before or after the filing of the patent application (a point about which the  
parties disagree), it was discovered that this protein stimulates only the growth of granulocytes,  
not other cell lineages. The protein subsequently became known as granulocyte colony-  
Page: 8  
stimulating factor [G-CSF]. Other than where this controversy is engaged (in the analyses of the  
misrepresentation and insufficiency allegations), these Reasons use the terms “hpG-CSF” and  
“G-CSF” interchangeably.  
[14] While the 537 Patent sets out 82 claims, Amgen’s allegations of infringement assert only  
Claims 43 though 47 [the Asserted Claims]. Subject to the defences it has pleaded, Pfizer admits  
that the making, constructing, using or selling of filgrastim would infringe the Asserted Claims.  
As such, the outcome of this action turns on Pfizer’s allegations of invalidity, all based on  
provisions of the Old Act, and the prior use defence.  
[15] Pfizer’s alleges three bases for invalidity: (a) the Asserted Claims are obvious; (b)  
Amgen has made wilfully misleading and untrue material allegations to CIPO, contrary to s 53 of  
the Old Act; and (c) the 537 Patent does not sufficiently disclose the alleged invention, contrary  
to s 34 of the Old Act. The prior use provision of the Old Act is s 56, although, for reasons that  
will be explained later, Pfizer relies on the common law to invoke that defence.  
[16] As a preliminary matter, this proceeding also raises an issue surrounding the interaction  
between an action under s 6(1) of the current Regulations and an application under the former  
Regulations related to the same patent. In 2012, Amgen brought such an application in Court File  
No. T-2072-12, seeking a prohibition order against the Minister of Health to prevent an NOC  
from issuing to Apotex Inc. [Apotex] for its filgrastim biosimilar [the Apotex Application]. In  
Amgen Canada Inc v Apotex Inc, 2015 FC 1261, Justice Hughes dismissed the Apotex  
Application, finding Amgen had not shown Apotex’s obviousness allegation in relation to Claim  
Page: 9  
43 of the 537 Patent was unjustified [the Apotex Decision]. Pfizer now argues this Court should  
adopt certain factual and legal findings of the Apotex Decision based on principles of abuse of  
process and/or judicial comity.  
[17] Each of the parties supported its positions on the various issues in this action through the  
evidence of expert witnesses. Each expert presented a report and was cross-examined at trial. All  
experts were qualified at trial without objection, with the articulation of the experts’ respective  
areas of qualification agreed between the parties. While Pfizer objected to various portions of  
Amgen’s experts’ evidence in advance of trial, including objections as to admissibility, the  
parties agreed the Court would receive the evidence and submissions on its admissibility at trial  
and adjudicate those objections in this Judgment and Reasons. Pfizer further advised during  
closing argument that it was pursuing objections to the expert evidence only as outlined in its  
closing submissions (all of which go to weight).  
[18] The parties also introduced evidence through fact witnesses. By agreement, they adopted  
a process whereby the witnesses’ direct evidence was presented in affidavit form, to be  
supplemented at the trial by a warm upexamination-in-chief, followed by cross-examination.  
One of Amgen’s witnesses, Dr. Hsieng Lu, was examined in advance of trial, with the video  
recording of the examination played and entered into evidence during trial.  
[19] The Asserted Claims in the 537 Patent read as follows:  
43. A polypeptide defined by the amino acid sequence:  
Page: 10  
Met Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu  
Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala  
Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro  
Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro  
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu  
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln  
Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr  
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln  
Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly  
Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly  
Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr  
Arg Val Leu Arg His Leu Ala Gln Pro [Claim 43 Sequence].  
44. A recombinant DNA encoding a polypeptide defined by the  
amino acid sequence: Claim 43 Sequence  
45. An expression vector comprising a DNA sequence encoding a  
polypeptide defined by the amino acid sequence: Claim 43  
46. A transformed host cell comprising an expression vector  
comprising a DNA encoding a polypeptide defined by the amino  
acid sequence: Claim 43 Sequence  
47. A process for the preparation of a human granulocyte-colony  
stimulating factor (G-CSF) comprising transforming a host cell  
with an expression vector containing a DNA sequence encoding  
the amino acid sequence: Claim 43 Sequence, culturing said  
transformed host cell and collecting the granulocyte colony-  
stimulating factor expressed by said transformed cell.  
[20] By the time of trial, the parties had significantly narrowed the issues originally identified  
in the pleadings and agreed on a Joint Statement of Issues. With some re-ordering/re-grouping  
and minor changes in their articulation, I adopt those issues as follows:  
A. Abuse of Process / Judicial Comity:  
i. Abuse of Process: Is it an abuse of process for Amgen to relitigate factual and  
legal issues determined by Justice Hughes in the Apotex Decision?  
Page: 11  
ii. Judicial Comity: If it is not an abuse of process, should this Court  
nevertheless follow the legal findings and/or factual findings from the Apotex  
Decision by reason of judicial comity?  
B. Validity:  
i. Skilled Person: Who is the person skilled in the art to whom the 537 Patent is  
addressed [the Skilled Person]?  
ii. Claim Construction: How should the Asserted Claims be construed?  
iii. Obviousness:  
(a) Date of Invention: Is August 23, 1985 the invention date of each of the  
Asserted Claims by virtue of the 959 Application? Or, was the subject  
matter of each of the Asserted Claims invented by no later than August 23,  
(b) Obviousness Analysis: Was each of the Asserted Claims obvious as of  
the date of invention?  
C. Material Misrepresentation: Is the 537 Patent void pursuant to section 53 of the Old  
D. Insufficiency: Is the disclosure of the 537 Patent insufficient pursuant to section 34 of  
the Old Act?  
E. Prior use defence: Is Pfizer exempt from liability for infringement by reason of  
section 56 of the Old Act?  
The following is a brief summary, identifying the background and role of each fact  
witness and the areas to which their evidence relates. While particular details of the evidence will  
be considered later in the Reasons, in analysing the issues to which it relates, I will include in  
this summary some detail intended to provide an overall factual framework. The following also  
identifies my general observations as to the reliability of the individual fact witnesses’ evidence.  
Page: 12  
A. Mr. Thomas Boone (Amgen Witness)  
1. Evidence in Brief  
[22] The first and lengthiest witness to give evidence on behalf of Amgen was Mr. Thomas  
Boone. Mr. Boone is a molecular biologist and protein chemist. In the 1970s, he received a  
Bachelor of Science degree in genetics and then two Masters of Science degrees, in genetics and  
soil science. Mr. Boone started working at Amgen Inc. in September 1981 as a Research  
Associate under Dr. Lawrence Souza (the named inventor on the 537 Patent) and reported to him  
for several years. He retired from Amgen in 2009 as its Vice President of Protein Sciences, the  
group within Amgen that focus on expressing, purifying, and developing proteins that can be  
used in human beings. Mr. Boone now owns his own consulting company, which consults for  
many companies including Amgen.  
[23] From 1981 through 1984, Mr. Boone worked as a Research Associate for Amgen,  
developing protocols and techniques for gene cloning and DNA sequencing, and working on  
projects focused on specific proteins. In this role, he developed experience in research strategies  
and molecular biology techniques involved in gene cloning, as well as experience with protein  
purification, both at the initial stage of isolating a naturally occurring protein and at the later  
stage of purifying a genetically engineered protein.  
[24] Mr. Boone first joined Amgen’s G-CSF project in late 1984. He was involved in this  
project through the clinical introduction of Amgen’s genetically engineered G-CSF in late 1986  
and continued to work with the protein into the early 1990s. He explains that the “kicking-off  
Page: 13  
point” for this project was a discovery made by a group of scientists at the Sloan-Kettering  
Institute [SKI] who were investigating the protein secreted by the 5637human bladder  
carcinoma cell line. Dr. Karl Welte and other scientists at SKI had observed that a protein  
preparation derived from the conditioned culture medium of 5637 cells had a stimulatory effect  
on blood cell precursors in certain types of in vitro assays. (While not expressly noted in Mr.  
Boone’s affidavit, the parties agree that this discovery was subsequently published in an article  
by Dr. Welte and others at SKI, entitled “Purification and biochemical characterization of human  
pluripotent hematopoietic colony-stimulating factor,” in the March 1985 edition of the  
Proceedings of the National Academy of Sciences [Welte 1985]).  
[25] Mr. Boone explains that the objective of Amgen’s G-CSF project was to attempt to clone  
the DNA for this protein and to design a process for expressing a genetically engineered (or  
recombinant) version of the protein, having the same biological activity as the naturally  
occurring variant. In his affidavit, he provides detailed explanations of Amgen’s process for  
attempting to produce the recombinant protein, broken down into the following five stages:  
A. obtaining an adequately purified sample of the naturally occurring G-CSF  
B. identifying a partial amino acid sequence of the protein;  
C. making a set of useful probes designed to bind to the cDNA (meaning  
complementary DNA) that encoded the identified partial amino acid sequence  
of the protein;  
D. identifying the gene (i.e. DNA sequence) that encodes the protein, by creating  
a cDNA library for the 5637 cell line and employing the probes to attempt to  
hybridize (i.e. bind) one of the probes to the targeted cDNA in the library;  
E. expressing a recombinant version of the G-CSF protein and purifying it in  
such a way that it retains at least some of the biological activities of the  
naturally occurring G-CSF protein.  
Page: 14  
[26] By the time Mr. Boone first joined the G-CSF project in late 1984, others on the Souza  
team had attempted throughout 1984 to obtain a partial amino acid sequence for the target  
protein by analysing samples of the conditioned medium that had been sent to Amgen by SKI,  
with which Amgen was collaborating. However, as adequate amino acid sequencing had not  
been achieved using the SKI samples, Dr. Souza decided Amgen would attempt to culture the  
5637 cells itself to create its own conditioned medium and then purify the relevant protein to  
undertake further sequencing efforts. This in-house work involved modifications to SKI’s  
original culturing and purification protocols as set out in Welte 1985. Mr. Boone was not directly  
involved in producing the conditioned medium. His work with the Souza team began with  
helping to purify Amgen’s in-house samples.  
[27] Mr. Boone’s affidavit details the challenges and uncertainties at the various stages of the  
G-CSF project. He emphasizes the very real possibility that the project would fail. Those  
challenges will be explained and considered later in these Reasons.  
(a) General Observations on Reliability  
[28] Pfizer submits the Court should treat Mr. Boone’s evidence with caution, arguing he is a  
paid advocate who has provided inconsistent and unreliable evidence. While Amgen no longer  
employs Mr. Boone, Pfizer notes he has worked with different Amgen legal teams on litigation  
involving the 537 Patent for years. Pfizer asserts that, while Mr. Boone is the witness Amgen has  
chosen to tell its invention story, he does not have first-hand knowledge of much of the evidence  
he seeks to provide to the Court. Pfizer also asserts that, by comparing Mr. Boone’s current  
Page: 15  
evidence with that which he provided in past proceedings, it is apparent he has both stretched  
and curated his evidence to favour Amgen’s position.  
[29] In support of this last assertion, Pfizer notes that Mr. Boone’s affidavit in the Apotex  
Application described Amgen’s changes to Dr. Welte’s purification protocol simply as  
refinements, while his current affidavit describes those changes as “significantly re-worked”.  
As another example, Pfizer refers to Mr. Boone’s evidence regarding the purification and proper  
folding of the recombinant G-CSF, which he describes as “[…] a difficult challenge for us to  
overcome in August 1985.” Pfizer points out that [REDACTED].  
[30] My overall impression of Mr. Boone was that he attempted to testify accurately and  
honestly. At times, he was less than direct in answering cross-examination questions, but I  
interpreted this as wanting to ensure precision in his answers, rather than as being difficult. That  
said, Pfizer’s points about Mr. Boone’s subjective characterization of Amgen’s work do resonate  
with me. Subject to concerns regarding evidence about which he does not have sufficient  
knowledge (which I will consider when addressing specific aspects of his evidence), I am  
inclined to treat his factual evidence surrounding Amgen’s work as reliable. However, I will treat  
his characterizations of that work with more caution.  
B. Dr. Krisztina Zsebo (Amgen Witness)  
1. Evidence in Brief  
[31] Dr. Krisztina Zsebo is a biochemist who worked at Amgen Inc. from April 1984 to 1992.  
She received a Bachelor of Science degree in biochemistry in 1977, a Masters degree in  
Page: 16  
biochemistry and biophysics in 1980, and a PhD in comparative biochemistry, with a minor in  
molecular biology, in 1984. Dr. Zsebo then joined Amgen as a Research Scientist. During her  
time at Amgen, she worked on the characterization, cloning, and/or recombinant expression of  
G-CSF and other factors. After the G-CSF project, she led the development of a stem cell factor,  
which was a hematopoietic growth factor like G-CSF. When Dr. Zsebo left Amgen in 1992, she  
was the Associate Director, Product Development for that stem cell factor. She is currently the  
Chief Executive Officer, Director, and Co-founder of a biotechnology company established in  
[32] Dr. Zsebo believes her involvement with the G-CSF project began sometime in April  
1985. She states she was heavily involved in the project and explains she was asked to provide  
information about that work, particularly the in vitro testing of the recombinant protein. Dr.  
Zsebo describes her involvement in the following aspects of the project:  
A. Beginning around April 1985, she joined the Souza team that had been  
working on culturing 5637 cells and helped Joan Fare, a research associate on  
that team, to produce the conditioned medium from which the target protein  
was purified;  
B. She conducted various in vitro tests, of both the purified target protein and  
Amgen’s E. coli expressed, recombinant version of the protein, to characterize  
the protein and to confirm that the team had recombinantly produced the  
correct protein. This involved setting up and running a number of in vitro  
biological assays, as well as determining the carbohydrate structure (or  
glycosylation) of the protein by identifying its apparent molecular weight;  
C. She helped to express a different version of the recombinant protein in  
mammalian cells (as opposed to E. coli cells); and  
D. She assisted Dr. Arthur Cohen, an Amgen research scientist specializing in the  
pharmacology of drug candidates, with in vivo testing of the E. coli expressed  
recombinant protein.  
Page: 17  
2. General Observations on Reliability  
[33] While Dr. Zsebo is not presently an Amgen employee, Pfizer notes she has acted as a  
consultant for Amgen in previous proceedings, including the Apotex Application.  
Notwithstanding that she may have an ongoing business relationship with Amgen, I identified no  
indications of bias or advocacy in her testimony. Dr. Zsebo struck me as a precise and  
straightforward scientist, and I found no basis to question her credibility. I remain conscious of  
arguments raised by Pfizer as to particular areas of her evidence that are not reliable, and I will  
take those into account when analysing her evidence in greater detail later in these Reasons.  
C. Dr. Hsieng Lu (Amgen Witness)  
1. Evidence in Brief  
[34] Dr. Hsieng Lu is a protein biochemist who worked at Amgen Inc. in its protein  
sequencing group from September 1984 until his retirement on December 31, 2013. Dr. Lu  
graduated with a Bachelor of Science in agricultural chemistry in 1970, a Masters of Science in  
1975, and a PhD in biochemistry in 1981. Protein sequencing was an important part of his thesis  
work, and he worked on several sequencing projects during his doctoral work from 1979 to  
1981. From 1982 to 1984, Dr. Lu completed post-doctoral work, focusing on the study of protein  
structure, protein function, and protein sequencing.  
[35] When Dr. Lu joined Amgen in 1984, he was the second research scientist to be recruited  
to its protein sequencing group. He joined another research scientist, Dr. Por Lai, who had  
already been working on the amino acid sequencing component of the G-CSF project. He  
Page: 18  
ultimately worked on the project with both Dr. Lai and two research assistants in the 1984 to  
1986 timeframe.  
[36] Dr. Lu explains the key responsibilities of the protein sequencing group were to  
determine the purity of protein samples provided to them and to try to determine the amino acid  
sequence of the protein of interest in each sample. With respect to cloning projects, the goal of  
the group was to determine, unambiguously, enough of the amino acid sequence of a protein of  
interest to permit Amgen’s molecular biologists to attempt to clone the protein. Dr. Lu explains  
the equipment and process through which this work was conducted.  
[37] In the period from March 1984 to late June 1985, Amgen’s protein sequencing group  
tried to sequence the target G-CSF protein five separate timesthree times using samples  
provided by SKI and twice using a protein sample independently purified by Amgen  
researchersbefore Dr. Souza was satisfied his team had a sufficiently long and unambiguous  
amino acid sequence to proceed with the cloning project. By the time Dr. Lu joined the group in  
September 1984, the three unsuccessful sequencing efforts (or runs) using the SKI samples had  
already taken place.  
[38] Dr. Lu states he was personally involved, with Dr. Lai, in the fourth and fifth runs using  
the sample purified in-house at Amgen. His involvement in the fourth run began on May 24,  
1985, when the protein sequencing group received a sample that had been partially purified by  
Mr. Boone from protein secreted by cells cultured in-house at Amgen. He and Dr. Lai performed  
the final purification stage, employing a High Performance Liquid Chromatography [HPLC]  
Page: 19  
system. Dr. Lu states that, from the fourth sequencing run, they were able to obtain a sequence of  
31 amino acids, most of which they were certain they identified correctly. However, Dr. Souza  
was not satisfied they could proceed with the cloning effort, and he directed the protein  
sequencing group to attempt another run on the same sample.  
[39] Therefore, in late June 1985, Amgen performed another sequencing run, using  
approximately 50% more of the sample than in the previous run. In addition to the increased  
amount of the sample, for the fifth sequencing run, the protein sequencing group decided to  
reduce the sample with ß-mercaptoethanol to remove the protein's secondary structure. That is,  
they unfolded the protein under reducing conditions, with the hope of improving the  
effectiveness of the process (called Edman degradation) by which they cleaved individual amino  
acids from the protein chain, allowing them to call additional amino acids. Dr. Lu also states that,  
after weighing the pros and cons of using polybrene, which could sometimes make sequencing  
calls more difficult due to the presence of impurities, Dr. Lai made the judgment call to use  
polybrene at each cycle of the Edman degradation to try to improve the identification of the  
amino acids of interest.  
[40] Dr. Lu explains they were then able to determine the identity of 44 amino acids before  
the chromatograms became too difficult to interpret. Based on the results of this fifth run, Dr.  
Souza was satisfied the amino acid sequence was sufficiently long and unambiguous that he  
could rely on it to move forward to the next steps of the cloning project. In his affidavit, Dr. Lu  
describes Dr. Souza and Mr. Boone selecting from this fifth run sequence a particular span of  
amino acids to design oligonucleotide probes. He also describes the sequencing group’s  
Page: 20  
uncertainty as to their results in the fifth run. In his view, Amgen was lucky that Dr. Souza chose  
the particular span that he did, as it later turned out that there were errors elsewhere in this fifth  
run sequence.  
2. General Observations on Reliability  
[41] Pfizer questions the level of first-hand involvement by Dr. Lu in the G-CSF project and  
the reliability of the recollections he claims to have of events that took place almost 35 years ago.  
It also emphasizes a portion of Dr. Lu’s cross-examination, which Pfizer characterizes as  
follows: “Dr. Lu made up evidence that was wholly untrue, and was forced to recant when  
confronted with his fabrication.”  
[42] This argument relates to Dr. Lu’s responses to questions by Pfizer’s counsel as to  
whether an affidavit he swore in the Apotex Application attached all the same exhibits as his  
affidavit in the present proceeding. After reviewing the documents during a break, Dr. Lu  
testified that certain chromatograms attached to his Apotex affidavit were not attached to his  
current affidavit. When asked if these omissions were an unintentional oversight, Dr. Lu  
responded that probably an intentional decision was made to remove the chromatograms to  
reduce complexity.  
[43] However, a short time later in the cross-examination, Dr. Lu located the missing  
chromatograms in the current affidavit, concluding they had all been included, just in a different  
order than in the Apotex affidavit. Under further questioning, Dr. Lu acknowledged that his  
Page: 21  
previous evidence, stating a decision had been made not to include certain chromatograms, was  
not true.  
[44] Amgen argues that Pfizer has unfairly accused Dr. Lu of being untruthful. Amgen  
submits this allegation of dishonesty does not relate to any statement material to the issues in this  
litigation. Nor did it represent an effort to distort evidence in Amgen’s favour. Amgen also  
asserts that Dr. Lu was initially speculating that a decision had been made to remove certain  
chromatograms from his present affidavit, and he described an actual recollection of such a  
decision only after being pressed by Pfizer’s counsel.  
[45] I agree with Pfizer that this portion of Dr. Lu’s testimony raises concerns about his  
reliability as a witness. The point is not that this evidence was material to the issues. Rather, the  
concern is whether the Court can rely on Dr. Lu’s professed recollections of events. While  
Pfizer’s counsel pressed Dr. Lu to confirm whether the decision to leave out certain documents  
was speculation or an actual recollection, I consider the pursuit of this questioning to have been  
entirely fair, given the ambiguity in the manner he described this decision.  
[46] I am not left with the impression of a deliberately dishonest witness, but rather of a  
witness who is prone to speculation and influence, and who cannot necessarily be relied upon to  
testify with precision as to what he actually remembers. Regardless, little actually turns on this  
impression. Amgen’s closing submissions actually rely very little on the evidence of Dr. Lu. As  
will be noted later in these Reasons, Amgen does emphasize in its obviousness submissions his  
evidence that one of the amino acids within the stretch selected by Dr. Souza and Mr. Boone  
Page: 22  
(residues 23-30) to design oligonucleotide probes had been mis-called in the fourth run.  
However, this fact does not itself appear to be controversial.  
D. Ms. Anita Hammer (Amgen Witness)  
[47] Ms. Anita Hammer is the Director of Regulatory Affairs at Amgen Canada, which she  
explains is an indirectly wholly-owned subsidiary of Amgen Inc. Like the other fact witnesses,  
she provided direct evidence through an affidavit. However, as agreed between the parties, she  
was not called as a viva voce witness at trial and was not cross-examined. Pfizer raises no  
concerns with the veracity of her evidence.  
[48] Ms. Hammer is responsible for completing regulatory requirements to list Amgen’s  
patents on Health Canada’s Patent Register, including the 537 Patent. She explains that process,  
including the means by which Amgen Canada obtained the consent of Amgen Inc. as patent  
[49] Ms. Hammer also explains that Dr. Souza, the named inventor of the 537 patent, left  
Amgen’s employ in 2000. She describes her unsuccessful efforts to contact Dr. Souza, through  
his legal counsel, to discuss his possible participation as a witness in the trial of this action.  
[50] Finally, Ms. Hammer describes contacting Joan Fare, a former Amgen employee who  
worked on the G-CSF project. [REDACTED].  
Page: 23  
E. Ms. Sheila Ahmed (Pfizer Witness)  
[51] Ms. Sheila Ahmed is a Manager, Regulatory Affairs at Pfizer, a subsidiary of Pfizer Inc.,  
and has worked in a regulatory role since 2015. Her responsibilities include managing Pfizer’s  
Canadian regulatory portfolio for biosimilars. She prepares and files regulatory submissions to  
Health Canada, including Pfizer Canada’s NDS concerning its filgrastim product NIVESTYM,  
which was filed on February 28, 2018.  
[52] Ms. Ahmed’s affidavit attaches excerpts from the NDS for NIVESTYM, copies of the  
product monographs for both NIVESTYM and Amgen’s drug NEUPOGEN, and Health  
Canada’s letter to Pfizer Canada dated February 8, 2019, advising that the review of its  
NIVESTYM submission was complete, but that an NOC would not be issued until the  
requirements of the Regulations are met. By agreement of the parties, Ms. Ahmed did not  
provide oral evidence at trial and was not cross-examined. Amgen raises no concerns about her  
F. Dr. Goran Valinger (Pfizer Witness)  
[53] Dr. Goran Valinger is the Director of Manufacturing Science and Technology at Hospira  
Zagreb d.o.o [Hospira Zagreb], which is a subsidiary of Pfizer. He holds both an undergraduate  
degree and a PhD in biotechnology. Dr. Valinger worked at PLIVA, a pharmaceutical company  
in Croatia, in various positions between 2001 and 2009. In 2006, he became the Director of  
Biotechnology Development, assuming responsibility for drug substance process development,  
including for filgrastim. In 2009, PLIVA was acquired by Hospira Inc. [Hospira], and Dr.  
Page: 24  
Valinger became the Director of Technical Support of Hospira Zagreb. In 2015, Pfizer acquired  
Hospira, and Dr. Valinger received his current title of Director of Manufacturing Science and  
Technology with Hospira Zagreb.  
[54] Dr. Valinger explains Hospira Zagreb will manufacture the filgrastim to be sold by Pfizer  
Canada. He also explains the manufacturing process, employing a system with two cell banks  
(called a two-tiered cell banking system). The first tier is a Master Cell Bank [MCB], comprising  
E. coli host cells that were transformed by expression vectors containing the DNA sequence  
coding for filgrastim. The second tier is a Working Cell Bank [WCB], created by replicating  
cells from the MCB. The cells of the WCB are in turn grown to make additional cells, called  
production cells, which are used to make filgrastim. The MCB, WCB, and production cells are  
all identical.  
[55] Dr. Valinger states that the MCB was created on or about April 6, 2004, the first WCB  
was created on or about April 19, 2005, and the first filgrastim protein was produced by  
December 23, 2005. Amgen does not challenge the reliability of Dr. Valinger’s evidence.  
[56] Each of the parties introduced expert evidence in support of its respective positions on  
construction of the Asserted Claims and the various grounds of invalidity that are at issue,  
including opining on the credentials and characteristics of the Skilled Person, the state of the art  
as of August 23, 1985, and the common general knowledge [CGK] of the Skilled Person as of  
August 23, 1985 and July 31, 2007. The following is a summary of each expert’s qualifications  
Page: 25  
and the areas to which his evidence relates. As with the above fact witnesses, I will include in  
these summaries some level of detail, intended to support analysis of the issues later in these  
Reasons. The following also identifies my general observations as to the reliability of the  
individual experts.  
A. Dr. Richard Van Etten (Pfizer Expert)  
[57] The first expert to testify on Pfizer’s behalf, Dr. Richard Van Etten, is presently the  
Director of the Chao Family Comprehensive Cancer Center and a Professor of Medicine and  
Biological Chemistry at the University of California Irvine. He also practices medicine as a  
physician in the Division of Hematology/Oncology at the University of California Irvine Medical  
Centre. Dr. Van Etten’s academic research and clinical practice is focused on cancers of the  
human blood system.  
[58] Dr. Van Etten earned Bachelor of Science degrees in Math and Biology from the  
Massachusetts Institute of Technology [MIT] in 1978 and a combined MD/PhD degree from  
Stanford University in 1984. He did his PhD research at Stanford from 1979 to June 1984 in the  
laboratory of Dr. David Clayton, who he describes as one of the world leaders in recombinant  
DNA technology. Dr. Van Etten then completed his internship and residency in Internal  
Medicine at Brigham & Women’s Hospital in Boston from 1984 to 1988 and a subsequent  
fellowship in hematology at the same hospital. Then, from 1988 to 1991, he conducted post-  
doctoral research at the Whitehead Institute for Biomedical Research at MIT. Dr. Van Etten’s  
research focused on the molecular structure and function of a particular protein involved in cell  
signalling that can cause chronic myeloid leukemia when it becomes dysregulated.  
Page: 26  
[59] Throughout his professional career, Dr. Van Etten has been a professor and researcher at  
several American universities, as well as practising medicine as a hematologist. For the past 27  
years, he has operated a research laboratory dedicated to the study of leukemias. Dr. Van Etten  
has authored many peer-reviewed publications, frequently presents at conferences, universities,  
and hospitals on the subject of his laboratory’s research, and has won many awards for that  
research. He was qualified at trial as an expert in hematology, protein biochemistry, and  
molecular biology, including recombinant DNA technology.  
[60] Dr. Van Etten provided two reports. In his first and principal report, he explains that  
Pfizer’s counsel assigned him several mandates. The following summarizes the mandates related  
to the issues in this action and Dr. Van Etten’s opinion in relation to each of them.  
1. Mandate 1 Welte 1985  
[61] First, Dr. Van Etten was asked to review and then summarize Welte 1985.  
[62] He describes Welte 1985 as reporting on the discovery and isolation of a human  
proteinwhich Dr. Welte named “pluripotent CSF”—that was reported to act as a pluripotent  
hematopoietic growth factor in the laboratory. Dr. Van Etten opines that this was a significant  
discovery in the area of hematology and of considerable interest to scientists in biotechnology  
companies, particularly those interested in developing drugs to treat disorders of the  
hematopoietic system.  
Page: 27  
2. Mandate 2 - Research following from Welte 1985  
[63] After he summarized Welte 1985, Pfizer’s counsel asked Dr. Van Etten if scientists at the  
time would have thought there was any research that naturally followed from Welte 1985. When  
he answered in the affirmative, counsel asked him what the next research project would be.  
[64] Dr. Van Etten responded that the last paragraph of Welte 1985 set out the next research  
project: to test the potential of “purified human pluripotent CSF […] in the management of  
clinical diseases involving hematopoietic derangement or failure.” To do so, Welte 1985  
suggests using recombinant DNA technology to allow for large-scale production of pluripotent  
CSF needed for clinical testing. Making recombinant pluripotent CSF for clinical testing would  
require two steps: (a) cloning the gene for pluripotent CSF; and (b) transforming the gene into  
host cells to cause them to produce biologically active pluripotent CSF.  
3. Mandate 3 - Literature related to steps after Welte 1985  
[65] After discharging Mandate 2, counsel asked Dr. Van Etten to identify sources of  
information scientists would have relied upon as of August 23, 1985 to carry out the recombinant  
expression of pluripotent CSF that he described in Mandate 2. Counsel asked him to focus on  
hematopoietic growth factors.  
[66] Dr. Van Etten responded that a flurry of activity between 1982 and 1986 led to the  
isolation of genes for several hematopoietic growth factors, including the protein described in  
Welte 1985. He opines that, by August 23, 1985, there were laboratory manuals that explained in  
detail the techniques necessary to carry out the recombinant expression of pluripotent CSF. A  
Page: 28  
laboratory manual entitled Molecular Cloning: A Laboratory Manual, authored by T. Maniatis  
and others in 1982 [Maniatis 1982], was the leading and comprehensive guide to recombinant  
DNA technology. Maniatis 1982 would have taught scientists how to use this technology to  
make proteins such as pluripotent CSF in large scale.  
4. Mandate 4 The 537 Patent  
[67] After completing the previous mandates, counsel provided Dr. Van Etten with a copy of  
the 537 Patent and asked him to: (a) summarize what the 537 Patent discloses; (b) identify the  
Skilled Person to whom the 537 Patent is addressed; (c) explain the Skilled Person’s CGK as of  
the July 31, 2007 publication date of the patent; and (d) opine how the Asserted Claims would  
have been understood by the Skilled Person as of July 31, 2007.  
[68] Dr. Van Etten opines that the 537 Patent begins where Welte 1985 left offit describes  
how Amgen made a recombinant form of the protein that Welte 1985 isolated. The patent  
renames this protein “hpG-CSF”. Dr. Van Etten states that the technical path described in the  
537 Patent for achieving recombinant expression of this protein is the path that he stated earlier  
in his report would naturally follow from Welte 1985: (a) cloning the gene for hpG-CSF; and (b)  
transforming the gene into host cells to produce recombinant hpG-CSF.  
[69] Dr. Van Etten concludes the Skilled Person to whom the 537 patent is addressed would  
have expertise in the fields of molecular biology, hematology, and protein biochemistry.  
Therefore, the Skilled Person would be a team, possessing the qualifications and experience to  
Page: 29  
understand and implement the teachings of the patent, consisting of one or more people with the  
following skills:  
A. a molecular biologist with a PhD and several years of work experience in  
academia or industry;  
B. a hematologist with an MD and board certification or, alternatively, a PhD in  
hematology and several years of work experience in academia or industry; and  
C. a protein biochemist with a PhD and several years of work experience in  
academia or industry.  
[70] Dr. Van Etten also provides scientific background information that he considers would  
have been included in the CGK of the Skilled Person as of the July 31, 2007 publication date of  
the 537 Patent. He explains this information was also CGK as of August 23, 1985, as the essence  
of protein biochemistry, molecular biology, and hematology had been largely worked out by  
1985, including the basic tools of recombinant DNA technology. However, he also explains that,  
between 1985 and 2007, there were significant advances in the CGK concerning hematopoietic  
lineages and growth factors, including hpG-CSF (which had become known as G-CSF). It was  
CGK by 2007 that the naturally occurring and recombinant versions of this protein did not in fact  
have pluripotent hematopoietic biological activity.  
[71] Dr. Van Etten then opines that the Asserted Claims claim the following:  
A. Claim 43 - a recombinant hpG-CSF polypeptide with the 174 amino acid  
sequence of naturally occurring hpG-CSF and an additional N-terminal  
methionine (Met) [the Claim 43 Polypeptide];  
B. Claims 44 to 46: recombinant DNA tools to express the Claim 43  
Polypeptide; and  
C. Claim 47: a process to make the Claim 43 Polypeptide.  
Page: 30  
[72] As discussed in more detail below, Dr. Van Etten finds the Skilled Person would not  
understand the polypeptide or tools in Claims 43-46 to possess any particular biological activity.  
However, the Skilled Person would understand the polypeptide resulting from the process of  
Claim 47 to possess granulocyte colony-stimulating activity.  
5. Mandate 5 - Obviousness  
Pfizer’s counsel then asked Dr. Van Etten whether any of the Asserted Claims were  
obvious. While he was asked to consider that question as of August 23, 1985 (the filing date of  
the 959 Application) and a subsequent date in 1986 (the filing date of the 548 Application),  
Amgen confirmed at trial that it is now relying only on the 1985 date.  
[74] Dr. Van Etten opines that all of the Asserted Claims were obvious as of August 23, 1985.  
He concludes that, after Welte 1985 was published, a Skilled Person would inevitably make a  
recombinant form of hpG-CSF so that its clinical potential could be explored. In Dr. Van Etten’s  
view, Welte 1985 clearly signalled the path forward, and the potential medical and commercial  
value of the protein was too great for this project not to have been pursued. He also concludes  
there was no inventiveness required to make this recombinant protein.  
[75] Dr. Van Etten opines that Amgen’s success in producing the recombinant protein was not  
surprising, as there were only a limited number of ways to use recombinant DNA technology to  
express the protein. After reading Welte 1985, the Skilled Person would have understood that  
achieving the goal of large-scale production of this protein would require the usual tools and  
standard techniques of recombinant DNA technology well known in the art. By August 23, 1985,  
Page: 31  
the Skilled Person would also have expected that recombinant hpG-CSF that was directly  
expressed in E. coli would likely have some or all of the biological activities of naturally  
occurring hpG-CSF.  
6. Mandate 6 - Priority Application  
[76] Counsel asked Dr. Van Etten whether the subject matter of the Asserted Claims is  
disclosed in the 959 Application. In Dr. Van Etten’s opinion, it is not, for two reasons:  
A. Each of the Asserted Claims relies on the amino acid sequence set out in  
Claim 43, which is different from the amino acid sequence in the 959  
Application. (This opinion relates to what it appears the parties agree are  
typographical errors in the sequence in the 959 Application.); and  
B. The 959 Application does not disclose that the recombinant protein has  
granulocyte colony-stimulating activity as set out in Claim 47 of the 537  
7. Mandate 7 - The Patent Specification  
[77] Counsel asked Dr. Van Etten to describe the invention of the 537 Patent and then asked  
whether the 537 Patent specification (being the description and claims) contains the information  
necessary to make use of the invention as of July 31, 2007 (the issue date).  
Page: 32  
[78] Dr. Van Etten describes the invention of the 537 Patent as the production of recombinant  
pluripotent granulocyte colony-stimulating factor, referring to the patent as being replete with  
references to pluripotency. He states that, by 2007, it had been clearly shown that naturally  
occurring and recombinant hpG-CSF did not have pluripotent hematopoietic biological activity.  
As such, the 537 Patent did not contain the information necessary to allow the Skilled Person to  
produce a granulocyte colony-stimulating factor with pluripotent activity.  
[79] Dr. Van Etten’s second report responds to the claim construction opinion of one of  
Amgen’s experts, Dr. Maloy. However, it became apparent at trial there are no material  
differences between the parties’ respective constructions of the Asserted Claims.  
8. General Observations on Reliability  
[80] I found Dr. Van Etten to be a forthright witness. Amgen does not contend that he (or  
indeed any of Pfizer’s experts) were dishonest or materially influenced by bias in any aspect of  
their opinions. Amgen acknowledges Dr. Van Etten was fair in responding to the propositions  
put to him by Amgen's counsel on cross-examination. Rather, Amgen submits that the  
differences between his opinion and its experts’ opinions predominantly reflect differences in  
their respective approaches to answering the same questions. Amgen argues its experts' evidence,  
and evidence elicited from Pfizer's experts on cross-examination, is the more germane to the  
legal tests relevant to the issues in this action. I will consider the specifics of the evidence of the  
parties’ respective experts later in these Reasons in relation to the individual issues to which it  
Page: 33  
B. Dr. Mark Hermodson (Pfizer Expert)  
[81] Pfizer’s next expert, Dr. Mark Hermodson, is a protein biochemist with experience in  
protein structure and amino acid sequence analysis, having worked in these disciplines since the  
1960s. Dr. Hermodson received a Bachelor of Arts degree in chemistry and mathematics in 1964  
and a PhD in biochemistry in 1968. He then conducted post-doctoral research at the University  
of Washington from 1969 to 1972, working with professors who ran one of the world’s largest  
amino acid sequencing laboratories. He spent most of his subsequent career at Purdue  
University, ultimately holding the position of Head of Biochemistry until 2001. He is the author  
of numerous peer-reviewed publications and estimates that, since 1977, he has personally  
conducted several hundred amino acid sequencings.  
[82] Dr. Hermodson explains that during the early-to-mid 1980s, when the work leading to the  
537 Patent was being performed, he was a Professor at Purdue University and actively engaged  
in protein biochemistry research and amino acid sequencing work. In particular, he managed a  
facility (often called a core facility) that conducted amino acid sequencing for other scientists.  
This work included, in particular, Edman degradation (a chemical reaction employed to remove  
each amino acid, one by one, from the protein chain to sequence that amino acid) and HPLC  
(which produces chromatograms that can be read to determine which amino acid has been  
Page: 34  
[83] Dr. Hermodson was qualified at trial as a protein biochemist with experience in amino  
acid sequencing. Pfizer’s counsel asked Dr. Hermodson to discharge two mandates. The  
following summarizes these mandates and Dr. Hermodson’s opinion in relation to each of them.  
1. Mandate 1 Review of Welte 1985  
[84] Counsel provided Dr. Hermodson with a copy of Welte 1985 and asked him to comment  
on the work done in that publication and what researchers working with proteins in 1985 would  
have done with the information in Welte 1985.  
[85] Dr. Hermodson concludes that Welte 1985 describes the successful isolation,  
purification, and characterization of a human pluripotent hematopoietic colony-stimulating factor  
(referred to as pluripotent CSF) from the human bladder carcinoma cell line 5637. He opines  
that researchers reading Welte 1985 would have recognized they could produce pluripotent CSF  
recombinantly using well-documented approaches that involved: (a) obtaining a partial amino  
acid sequence; (b) making oligonucleotide probes; (c) cloning the gene for pluripotent CSF; and  
(d) expressing pluripotent CSF in a host cell.  
2. Mandate 2 Review of the 537 Patent  
[86] After Dr. Hermodson reviewed Welte 1985 and commented on it, counsel provided him  
with the 537 Patent and asked him to comment on the amino sequencing work described therein,  
in light of the state of the art in 1985. Counsel specifically asked Dr. Hermodson whether any of  
that work would have been outside the normal level of technical skill expected of the Skilled  
Person as of August 23, 1985.  
Page: 35  
[87] After receiving instructions as to the nature of the Skilled Person, he opines the patent is  
addressed to a protein biochemist with a PhD and several years of work experience in a  
discipline related to protein biochemistry. He explains that the skilled protein biochemist may  
oversee the work of a technician operating the sequencer (a machine that, by 1985, was widely  
used to perform Edman degradation) and HPLC column. Dr. Hermodson also provides scientific  
background information that he considers would have been included in the CGK of the skilled  
protein biochemist.  
[88] The 537 Patent sets out in several Examples the steps undertaken by Amgen in producing  
the recombinant protein. As Dr. Hermodson’s expertise relates to the amino acid sequencing  
step, he reviews Example 1, which sets out the process used for amino acid sequencing of the  
target protein. He reviews the information disclosed in the patent related to each of the five  
sequencing runs and concludes the 537 Patent does not describe any amino acid sequencing work  
that was outside the abilities of an ordinary skilled protein biochemist as of August 23, 1985. He  
opines that, through successive runs, Amgen used the same iterative process for amino acid  
sequencing that was used by skilled biochemists at the time.  
3. General Observations on Reliability  
[89] As with Dr. Van Etten, Amgen does not contend Dr. Hermodson was materially  
influenced by any bias in any aspect of his opinions, and it acknowledges he was fair in  
responding to the propositions put to him by Amgen's counsel on cross-examination. Consistent  
therewith, I found him to be a straightforward and knowledgeable witness.  
Page: 36  
C. Dr. Steven Boxer (Pfizer Expert)  
[90] Dr. Steven Boxer is currently the Camille Dreyfus Professor of Chemistry at Stanford  
University. Since he started his laboratory at Stanford in 1976, the focus of his research has been  
investigating and researching the structure of biological systems, particularly proteins. Dr.  
Boxer’s education includes a Bachelor of Science degree in Chemistry, earned in 1969, and a  
PhD in Physical and Physical-Organic Chemistry, earned in 1976. He has spent his academic  
career at Stanford University, where he became an Associate Professor in 1982 and a Full  
Professor in 1986. He has held his current position since 2000. Dr. Boxer has received many  
awards and has served as a member or elected fellow of several scientific organizations. He has  
authored over 325 publications, mostly in peer-reviewed journals, and has been invited to present  
his research at universities and scientific conferences around the world.  
[91] Dr. Boxer was qualified at trial as an expert in protein biochemistry and molecular  
biology including recombinant DNA technology. Like Dr. Van Etten, he provided two reports,  
the second of which responds to the claim construction opinion of Amgen’s expert Dr. Maloy,  
However, as previously noted, there are no material differences between the parties’ positons on  
claim construction. In Dr. Boxer’s first and principal report, he addresses the following four  
Page: 37  
1. Mandate 1 - Welte 1985  
[92] Pfizer’s counsel provided Dr. Boxer with a copy of Welte 1985. They asked him to  
review and summarize the article and provide his opinion on what, if any, research a Skilled  
Person would have wanted to pursue following the publication of this article.  
[93] Dr. Boxer explained that Welte 1985 describes the isolation of a human protein called  
human pluripotent hematopoietic colony-stimulating factor (or pluripotent CSF) that is said to be  
involved in hematopoiesis. Welte 1985 also describes some aspects of the purified protein’s  
structure and function.  
[94] Dr. Boxer’s opinion is that, following the publication of Welte 1985, the Skilled Person  
would have wanted to determine if pluripotent CSF had clinical promise. The Skilled Person  
would recognize that clinical testing would require large amounts of the protein and that the  
fastest and cheapest way to make large amounts was recombinant DNA technology. Therefore,  
the next logical steps would be for the Skilled Person to: (i) clone the gene for pluripotent CSF;  
and (ii) use the cloned gene to express recombinant pluripotent CSF in E. coli.  
2. Mandate 2 The 537 Patent  
[95] After providing his opinion on Mandate 1, Dr. Boxer was provided with a copy of the  
537 Patent. He was asked to summarize it and opine on how the Asserted Claims would have  
been understood by the Skilled Person as of July 31, 2007.  
Page: 38  
[96] Dr. Boxer describes the 537 Patent as presenting the work that he expected would follow  
from Welte 1985, that is: (i) the cloning of the gene for pluripotent CSF (which the inventor  
renames hpG-CSF); and (ii) the recombinant expression of this protein in E. coli. He construes  
the Asserted Claims as follows:  
A. Claim 43: a recombinant polypeptide;  
B. Claims 44 to 46: tools to express that polypeptide in a host cell such as E.  
C. Claim 47: a general process for making a biologically active form of the  
Dr. Boxer notes that the polypeptide has the amino acid sequence of naturally occurring hpG-  
CSF, but with an additional N-terminal methionine (i.e., a particular amino acid at one end of the  
amino acid chain), which is required for expression in E. coli.  
3. Mandate 3 Obviousness of Claim 43  
[97] Pfizer’s counsel asked Dr. Boxer to opine whether Claim 43 was obvious as of August  
23, 1985, focusing in particular on the portion of the process following isolation of the gene  
encoding naturally occurring hpG-CSF. He was also asked to provide this opinion with an  
additional assumption that the claimed polypeptide had to have one or more of the biological  
activities of naturally occurring hpG-CSF.  
[98] In conducting this analysis, Dr. Boxer opines that the relevant CGK of the Skilled Person  
would include an understanding of the fundamentals of molecular biology and protein  
biochemistry, which would include the available tools and techniques of recombinant DNA  
Page: 39  
technology and protein biochemistry as of August 23, 1985. Earlier in his report, Dr. Boxer also  
states that the CGK included the following standard laboratory processes:  
A. determining a partial amino acid sequence for a target protein;  
B. using that partial amino acid sequence to make a probe that targeted the gene  
for the protein; and  
C. using the probe to isolate the gene for the protein from a cDNA library.  
[99] Dr. Boxer concludes Claim 43 was obvious as of August 23, 1995. Starting with the  
cloned gene, it would have been obvious to make recombinant hpG-CSF using direct expression  
in E. coli. It was standard practice to express mammalian proteins in E. coli by direct expression,  
and the Skilled Person would have anticipated that approach would work. Dr. Boxer also opines  
that the work described in the 537 Patent uses standard tools and procedures that were well  
[100] His conclusion remains the same if the polypeptide had to have one or more of the  
biological activities of naturally occurring hpG-CSF, as the Skilled Person would have expected  
the polypeptide to have such biological activity. As discussed in more detail below, Dr. Boxer is  
confident the Skilled Person would be able to purify and properly fold the polypeptide after  
direct expression in E. coli, so that it had biological activity. Welte 1985 provided information  
about the secondary and tertiary structure of the naturally occurring protein, which would  
encourage the Skilled Person about the recombinant protein’s potential biological activity.  
Page: 40  
4. Mandate 4 - Obviousness of Claims 44 to 47  
[101] Finally, Dr. Boxer was asked whether Claims 44 to 47 were obvious as of August 23,  
1985, again focusing on the portion of the process following isolation of the cloned gene. He  
concludes these claims were obvious for the same reasons as Claim 43. The tools claimed in  
Claims 44 to 46 and the process claimed in Claim 47 were commonplace and therefore added  
nothing inventive to the Claim 43 polypeptide.  
5. General Observations on Reliability  
[102] As with Pfizer’s other experts, Amgen does not contend that Dr. Boxer was materially  
influenced by any bias in any aspect of his opinion. I found him to be a credible and  
knowledgeable witness.  
D. Dr. Stanley Maloy (Amgen Expert)  
[103] Dr. Stanley Maloy is currently a Professor of Biology and the Associate Vice President  
for Research and Innovation at San Diego State University. He completed a Bachelor of Science  
degree in biological sciences in 1975, a Masters degree in microbiology in 1977, and a PhD in  
molecular biology and biochemistry in 1981. He conducted post-doctoral research until 1984,  
and then joined the faculty of the University of Illinois Urbana-Champaign as an Assistant  
Professor, leaving that institution as a full professor in 2002. His teaching focused on molecular  
genetics, and his research focused on genetics and biochemistry of membrane proteins. In the  
1985-1986 timeframe, Dr. Maloy was actively researching in the fields of molecular biology and  
Page: 41  
biochemistry and had been doing so for a decade. He was also knowledgeable about  
developments in hematology and protein chemistry.  
[104] Dr. Maloy has held leadership positions with the American Society for Microbiology, the  
Center for Microbial Sciences, the Center for Applied and Experimental Genomics, and the  
American Academy for Microbiology, and has authored numerous scientific publications and  
books. He was qualified at trial as an expert in microbiology, biochemistry, molecular biology  
and genetics, including recombinant DNA technology. Dr. Maloy notes that he does not consider  
himself an expert in protein sequencing, although he explains he is generally knowledgeable in  
that area, as he has experience accessing protein sequencing services in connection with his  
research projects.  
[105] Dr. Maloy authored two reports on this matter. The first involves claim construction,  
providing his opinion on the characteristics of the person to whom the 537 Patent is addressed, as  
of July 31, 2007, and how that person would have understood the Asserted Claims. His second  
report responds to the reports of Drs. Van Etten, Boxer, and Hermodson, addressing particular  
tasks assigned to him by Amgen’s counsel. His opinions in relation to the tasks relevant to the  
issues in this action are summarized below.  
1. Report 1 Construction Report  
(a) Skilled Person  
[106] In Dr. Maloy’s opinion, in 2007, the 537 Patent is addressed to a research scientist with a  
PhD in the field of molecular biology, biochemistry, hematology, or protein chemistry; graduate  
Page: 42  
students with at least three years of research experience in the fields of molecular biology,  
biochemistry, hematology, and protein chemistry; or an MD with a focus on research and at least  
two years of relevant, post-doctoral research that includes molecular biology, biochemistry,  
hematology, or protein chemistry.  
(b) Claim Construction  
[107] Dr. Maloy opines the Asserted Claims relate to a process for preparing a functional,  
synthetic version of human granulocyte colony-stimulating factor, the DNA sequence,  
expression vector and transformed host cell used in that process, and the polypeptide resulting  
from that process. He provides more detailed constructions for each of the individual Asserted  
Claims. However, as explained later in these Reasons, there is no material disagreement between  
the parties surrounding construction of the Asserted Claims. It is therefore not necessary to  
review this aspect of Dr. Maloy’s opinion in any detail.  
2. Report 2 Validity Report  
(a) Identity of the Skilled Person  
[108] In his second report, Dr. Maloy was first asked to identify the Skilled Person as of August  
23, 1985 (as well as dates in 1986 that are no longer relevant to this action). He disagrees with  
Dr. Van Etten’s description of the Skilled Person, as he considers the Skilled Person described  
by Dr. Van Etten to have the same experimental skill as an expert in the field, lacking only their  
inventiveness. Dr. Maloy describes the person of ordinary skill as having less education or  
experience than Dr. Van Etten’s Skilled Person.  
Page: 43  
(b) Knowledge of the Skilled Person  
[109] Asked about the Skilled Person’s CGK, in particular what the Skilled Person would have  
understood from Welte 1985 and Maniatis 1982, Dr. Maloy substantially agrees with Dr. Van  
Etten’s and Dr. Boxer’s identification of the various laboratory tools and techniques that would  
have been available to the Skilled Person. He also agrees that, by August 1985, there were  
published examples in which various combinations of these tools and techniques had been used  
to genetically engineer a recombinant version of a naturally occurring protein.  
[110] However, Dr. Maloy states that in August 1985 recombinant protein expression was a  
long and complex process that was fraught with difficulty. He agrees that many of the tools and  
techniques involved in the gene cloning process could individually be characterized as standard  
or routine (noting as an exception the use of inosine probes, a technique that is explained later in  
these Reasons). Nevertheless, he opines that devising and successfully executing a strategy for  
how to combine those tools and techniques to clone a gene for a protein and express a functional  
recombinant version of the protein for the first time was not routine in August 1985.  
(c) Information Disclosed by the 537 Patent  
[111] Dr. Maloy was asked to summarize the information disclosed by the 537 Patent that is  
relevant to Claims 43 to 47, and that would not have been known to the Skilled Person. He  
opines that the patent discloses the 174 amino acid sequence of the naturally occurring colony-  
stimulating factor G-CSF and discloses a process for making biologically active recombinant G-  
Page: 44  
(d) Obviousness  
[112] Next, Dr. Maloy was asked to consider whether the invention claimed in each of the  
Asserted Claims would have been obvious to the Skilled Person on August 23, 1985. He  
concludes the claims were not obvious. Specifically, Dr. Maloy opines that the amino acid  
sequence of G-CSF, and the process for making biologically active recombinant G-CSF, had not  
yet been discovered and were determined by Dr. Souza through a series of experiments that were  
not obvious to try. While he agrees there would have been a strong motive to clone and  
recombinantly express the gene of the protein identified by Welte 1985, there was no roadmap  
available to the Skilled Person that would have led them directly and without difficulty to  
achieving that objective.  
[113] Dr. Maloy acknowledges published examples in which other genes were successfully  
cloned and other proteins expressed recombinantly. These would have provided the Skilled  
Person with ideas for what could be tried. However, Dr. Maloy opines that the Skilled Person  
would not have expected that what worked for a different protein ought to work for G-CSF. He  
states that, even within the narrow realm of hematopoietic growth factors (like G-CSF), there  
was no single cloning strategy that had consistently worked. Further, most of the strategies that  
had worked were significantly different from the strategy that the Souza team successfully  
executed for cloning and recombinantly expressing the gene for G-CSF.  
Page: 45  
(e) Response to Pfizer’s Experts’ Claim Construction  
[114] Dr. Maloy responds to Dr. Van Etten’s and Dr. Boxer’s opinions as to how the Asserted  
Claims would have been understood (by what he refers to as the skilled reader) as of July 31,  
2007. He generally agrees with their opinions. However, he disagrees with a statement (related to  
Claim 44) by Dr. Van Etten that there is no limit to what the DNA sequence can be in the  
recombinant DNA as long as it includes sequences encoding the Claim 43 polypeptide. Dr.  
Maloy responds that, while the Skilled Person would appreciate the degeneracy of the genetic  
code (i.e. that different DNA sequences could code for the same polypeptide sequence), this  
reading would not have allowed for an unlimited DNA sequence in Claim 44 or the subsequent  
claims. However, this difference between those experts’ opinions does not appear to be material  
to any of the arguments the parties are advancing.  
(f) 959 Application  
[115] Asked to consider whether the 959 Application disclosed the same invention as Claim 47,  
including the granulocyte colony-stimulating activity that is part of the invention of Claim 47,  
Dr. Maloy concludes that it did. He opines that the Skilled Person would have understood the  
amino acid sequence in the 959 Application, realizing that it contained typographical errors and  
logically overcoming those errors. Also, while Claim 47 of the 537 Patent claims a process that  
allows production of a functional polypeptide having granulocyte-stimulating activity, the 959  
Application showed that the functional polypeptide had granulocyte-stimulating activity when  
properly folded.  
Page: 46  
(g) Sufficiency  
[116] Asked to consider whether the 537 Patent Specification contains the information  
necessary to produce “pluripotent granulocyte colony-stimulating factor” as of July 31, 2007, Dr.  
Maloy concludes that it does. He opines that, by July 31, 2007, the Skilled Person would have  
understood that the “pluripotent granulocyte colony-stimulating factor” described in 1985  
referred to “granulocyte colony-stimulating factor”, which the 537 Patent specification contains  
the information necessary to produce.  
3. General Observations on Reliability  
[117] In addition to several criticisms of the depth of Dr. Maloy’s expertise and the  
methodology he employed in arriving at his opinions, Pfizer submits Dr. Maloy acted more as an  
advocate for Amgen than as an independent and impartial expert. While not all the points raised  
by Pfizer in support of this submission resonate with me, some do raise concerns that Dr. Maloy  
strayed into the role of an advocate. The following are the most compelling examples of this  
[118] One of the cloning techniques upon which both parties focus significantly is the use of  
inosine probes, because this technique had been developed only shortly before Amgen’s work on  
the G-CSF project. This tool will be explained in greater detail later in these Reasons. For  
present purposes, the point is that Dr. Maloy asserts the use of inosine probes was not routine in  
1985. In support of this assertion, he observes how long it took for the technique to appear in the  
handbook by Maniatis: “… it is telling that inosine probes were not included in the handbook  
Page: 47  
until the 1989 edition.” However, on cross-examination, Dr. Maloy acknowledged there were no  
editions of Maniatis between 1982 and 1989.  
[119] I agree with Pfizer’s argument that Dr. Maloy’s language suggests there were editions of  
Maniatis between 1985 and 1988 that did not include any reference to inosine probes, supporting  
his assertion the technique was not routine. In fact, the length of time that elapsed before these  
probes appeared in Maniatis was a function of the fact that 1989 was the next edition published  
after such probes were first developed and reported on in 1985. This aspect of his evidence  
supports Pfizer’s assertion that Dr. Maloy demonstrated a tendency towards advocacy.  
[120] I have a similar concern about the manner in which Dr. Maloy describes Amgen’s  
purification procedure when it created its in-house samples of the target protein. He describes  
Amgen’s protocol as a complete reworkof the purification procedure described in Welte 1985.  
Following his statement of that opinion, Dr. Maloy provides in table form a summary of the  
differences between the Welte and Souza procedures. However, in cross-examination, Dr. Maloy  
acknowledged some of the items in the table used different terms to describe the same substance  
or technique.  
[121] Amgen responds to this argument by pointing out that, in his warm-updirect  
examination, Dr. Maloy identified some of the items in the table represented similarities and  
others represented differences. Pfizer, in turn, asserts Dr. Maloy’s oral evidence was an effort to  
improve his written evidence, because Pfizer had telegraphed in opening submissions that they  
Page: 48  
would be challenging Dr. Maloy’s opinion that Amgen’s purification process was a complete  
[122] I find Pfizer’s argument the more compelling. Dr. Maloy’s report clearly describes the  
table as a summary of the differences between the procedures of Drs. Welte and Souza.  
Moreover, the next paragraph of Dr. Maloy’s report refers to this “particular combination of  
changes” as not being obvious to the Skilled Person. It is at best severely lacking in precision for  
Dr. Maloy to have supported an important element of his opinion in this manner and raises  
concern that, consciously or not, Dr. Maloy’s work has strayed into advocacy. My concern does  
not rise to the level that I will necessarily prefer the evidence of other witnesses over Dr. Maloy,  
particularly if his evidence on a particular point is compelling for other reasons. However, I will  
treat his evidence with caution.  
E. Dr. David Speicher (Amgen Expert)  
[123] Dr. David Speicher is a protein biochemist, currently the Caspar Wistar Professor of  
Computational and Systems Biology at The Wistar Institute [Wistar] in Philadelphia, PA. Since  
1986, he has also been the Scientific Director of the Proteomics and Metabolomics Core Facility  
at Wistar. He is the Co-chair of the Molecular & Cellular Oncogenesis Program and the Director  
of the Center for Systems and Computational Biology. Dr. Speicher is also an adjunct professor  
in the Department of Biochemistry and Biophysics at the University of Pennsylvania and an  
adjunct professor of Biochemistry and Molecular Medicine at Drexel University.  
Page: 49  
[124] Dr. Speicher received his undergraduate degree in biochemistry in 1972 and his PhD in  
biochemistry in 1977. He then received post-doctoral training at the Yale University School of  
Medicine and was promoted to Research Scientist in 1984. From 1980 to 1986, he was also  
Director of the Protein Chemistry Laboratory at the Yale School of Medicine, a core facility that  
provided protein sequencing, amino acid analysis, and HPLC technologies to Yale University  
faculty. Dr. Speicher has published numerous peer-reviewed papers, has acted in an editorial  
capacity for many scientific publications, and has authored numerous book chapters and reviews.  
He is also a member of several relevant professional organizations. He was qualified at trial to  
give expert opinion evidence in the fields of protein chemistry and amino acid sequencing.  
[125] Having been asked by Amgen’s counsel to discharge three mandates, Dr. Speicher’s  
opinions can be summarized as follows:  
1. Mandate 1 Skilled Person and Common General Knowledge  
[126] Focusing in particular on Example 1 of the 537 Patent, which relates to his area of  
expertise, Dr. Speicher opines this Example is addressed to a biochemist with an advanced  
degree related to protein biochemistry. Such a person would have a PhD with two years of  
experience or a Masters degree with substantially more years of relevant experience.  
[127] Dr. Speicher identifies the CGK possessed by that Skilled Person as comprising the  
general approaches to protein purification and partial amino acid sequencing in 1985; the  
operation of automated Edman degradation amino acid sequencers; and some ability to make  
Page: 50  
callsof partial amino acid sequences when provided a sufficient amount of a sufficiently pure  
experimental protein that produced strong and straightforward signals.  
[128] Dr. Speicher further opines that, armed with that CGK, the number of contiguous  
residues (i.e. amino acids) a Skilled Person would be able to correctly assign in an experimental  
protein sequence would vary substantially depending upon the protein’s properties, but the  
length of sequence determined would typically not be extensive and may or may not be sufficient  
to allow the construction of oligonucleotide probes.  
2. Mandate 2 Obviousness of Example 1 of the 537 Patent  
[129] Next, Amgen’s counsel asked Dr. Speicher to review Amgen’s protein purification and  
amino acid sequencing work as described in Example 1 of the 537 Patent and to opine whether  
the Skilled Person could successfully carry out that work as of August 1985 without ingenuity,  
inventiveness or creativity.  
[130] Dr. Speicher concludes this work required substantial specialized skill, judgment, and  
creativity and was beyond the capabilities of the Skilled Person as of August 23, 1985. He opines  
it would not have been more or less self-evident to the Skilled Person that any accurate N-  
terminal amino acid sequence information could be obtained. Even if a partial sequence could be  
obtained, it would not have been more or less self-evident that the sequence would correspond to  
the N-terminus of the protein (and biological activity) that the researchers were attempting to  
identify, or that the sequence would be sufficiently long, unambiguous, or useful for a cloning  
Page: 51  
3. Mandate 3 Response to Pfizer’s Experts  
[131] Amgen’s counsel asked Dr. Speicher to review and further respond to the opinions  
provided by Drs. Hermodson, Van Etten and Boxer in their respective reports that fall within his  
expertise, indicating the areas of agreement and disagreement with those opinions.  
[132] Dr. Speicher strongly disagrees with the opinions of Drs. Hermodson and Van Etten that  
the amino acid sequencing work described in the 537 Patent was, respectively, straightforward  
and routine. He states that their opinions ignore the many challenges faced by the Skilled Person  
in correctly calling amino acid sequences of sufficient unambiguous length to render them useful  
in a cloning project, when working with small amounts of an unknown, experimental protein. He  
states that their opinions rely on several references reporting on the work of other protein  
biochemists and greatly exaggerate the abilities of the Skilled Person and what was routine in  
1985. Dr. Speicher describes many of the references cited by Pfizer’s experts as reporting on the  
work of extraordinarily skilled protein biochemists whose skills far exceeded the abilities of the  
Skilled Person.  
4. General Observations on Reliability  
[133] Dr. Speicher is the only expert witness in this matter who also gave evidence in the  
Apotex Application. Pfizer submits he is acting as an advocate, having changed his evidence  
from the Apotex matter to make the amino acid sequencing process appear more challenging, as  
well as adding new information favourable to Amgen’s case and removing other less favourable  
Page: 52  
[134] For example, Pfizer refers to Dr. Speicher’s testimony that Amgen’s amino acid  
sequencing Run 2 did not produce more information than the previous run, which conflicts with  
the opinion in his Apotex affidavit. Also, his current affidavit describes Amgen’s failed attempt  
on Run 3 as a highly innovative attempt, as it used a different sequencing method than the other  
runs, while his Apotex affidavit is silent on that run. In his Apotex affidavit, Dr. Speicher did not  
discuss the use of a reducing agent or a problem with loading protein sample onto the sequencer,  
but in his current affidavit, these are portrayed as matters of significance.  
[135] Pfizer also notes Dr. Speicher tried to distance himself from a statement in a patent of  
which he was a co-inventor, to the effect that since a particular protein had been purified to  
homogeneity, oligonucleotide probes can identify the relevant gene, thereby allowing the protein  
to be produced by known recombinant DNA techniques.  
[136] I do not find Pfizer’s submissions on these points particularly compelling. In my view,  
Dr. Speicher adequately explained in cross-examination the differences in language surrounding  
Run 2. With respect to Run 3, I accept Amgen’s submission that, in his current report, Dr.  
Speicher was providing a response to an opinion by Dr. Hermodson's opinion related to that run.  
Apotex’s expert had provided no similar opinion. I do not find the fact that Dr. Speicher offered  
opinions on some points that did not arise in the Apotex Application to undermine his reliability  
as a witness.  
[137] Nor does such a result arise from Dr. Speicher’s testimony surrounding his patent. He  
explained in cross-examination that, while he signed the patent application and considered its  
Page: 53  
details correct, he did not write the patent himself and did not agree with the particular statement  
from the patent put to him by Pfizer’s counsel. That testimony, and his demeanor generally, left  
me with the impression of an honest witness.  
[138] I therefore reject Pfizer’s submission to the effect that Dr. Speicher deliberately tailored  
his evidence to favour Amgen. Pfizer raises other arguments in support of its position that I  
should prefer the opinions of its experts to those of Dr. Speicher, which arguments I will address  
when considering the particular issues to which that evidence relates.  
F. Dr. James Griffin (Amgen Expert)  
[139] Dr. James Griffin is a Senior Physician at the Dana-Farber Cancer Institute and a  
Professor of Medicine at Harvard Medical School. He obtained his MD in 1974 and then  
completed a residency in medicine followed by a series of fellowships, including a research and  
clinical fellowship in hematology and a clinical and research fellowship in medical oncology. In  
1977, Dr. Griffin obtained board certification from the American Board of Internal Medicine. In  
1978, he obtained board certification in the hematology subspecialty, and in 1981 he obtained a  
further board certification in the medical oncology subspecialty.  
[140] Dr. Griffin has been a member of the faculty of Harvard Medical School and a member  
of the staffs of the Dana-Farber Cancer Institute and Brigham & Women’s Hospital since 1980.  
He has authored or co-authored numerous scientific publications, has contributed to reviews,  
commentaries and book chapters, has held dozens of roles on research committees and with  
professional societies, and has served on the editorial boards of several scientific journals. Dr.  
Page: 54  
Griffin has run his own independent laboratory at the Dana-Farber Cancer Institute since 1981,  
with major research focuses on the regulation of hematopoiesis and the biology and treatment of  
myeloid leukemia (a cancer affecting blood cells). He was qualified at trial as an expert in the  
areas of hematopoiesis and oncology.  
[141] Amgen’s counsel asked Dr. Griffin to provide opinions in the following areas, including  
responding to the report of Dr. Van Etten within his areas of expertise.  
1. Mandate 1 Identity of Skilled Person  
[142] Asked to identify the Skilled Person of the 537 Patent as of August 23, 1985, Dr. Griffin  
opined the Skilled Person would have the same advanced degrees as described by Dr. Van Etten,  
but less experience. In his opinion, the Skilled Person has one to three years post-graduate  
experience, is skilled enough to use the techniques in the area, and encounters the subject matter  
in the regular course of their work. Dr. Griffin refers to the Skilled Person seeking out expert  
advice in order to adapt things to their own use. He describes Dr. Van Etten's Skilled Person as  
more like an expert. Although Dr. Griffin states he has performed his analyses from the  
perspective of each of Dr. Van Etten's and his Skilled Person, his evidence does not demonstrate  
a distinct analyses from the perspective of a Skilled Person with less experience.  
2. Mandate 2 - State of the Art of Hematopoiesis in August 1985  
[143] Asked to describe the state of the art in the area of hematopoiesis relating to the subject  
matter of the 537 Patent before August 23, 1985, Dr. Griffin explains that CSFs were of great  
interest in the field of hematology and particularly hematopoiesis. At least four CSFs had been  
Page: 55  
identified, although there was no consistent nomenclature used to describe these CSFs and no  
agreed-upon identification of their functions.  
[144] Dr. Griffin states that expert teams at the leading edge of industry and academia were  
assembled to confront and overcome the difficulties associated with purifying CSFs isolated  
from the cells of humans and animals, and, if successful, to confront and overcome the  
difficulties associated with trying to clone the genes that code for those proteins. Each CSF  
presented a unique challenge. By 1985, several such groups were attempting to prepare partially  
purified human CSF preparations. Among these were SKI, under the supervision of Dr. Welte,  
and the Walter and Eliza Hall Institute [WEHI] of Australia, under the supervision of Dr. D.  
[145] The SKI lab had prepared a protein preparation of a human CSF that it identified as  
pluripotent CSF. The WEHI lab, using the same human cell line that the SKI lab had used,  
distinguished two different human CSFs, which it identified as “CSF-α” and “CSF-ß”. The  
WEHI lab identified that CSF-ß was the human analog of mouse G-CSF; and, like mouse G-  
CSF, CSF-ß specifically stimulated growth of granulocyte colonies. However, neither SKI nor  
WEHI had identified the equivalence of CSF-ß with pluripotent CSF, and neither group had  
published the entire amino acid sequence of either factor.  
3. Mandate 3 - 959 Application  
[146] Asked whether the 959 Application disclosed the same invention as Claim 47 of the 537  
Patentand, in particular, granulocyte colony-stimulating activity Dr. Griffin responded that  
Page: 56  
it did. Claim 47 claims a process for making biologically active recombinant G-CSF. The 959  
Application showed that Amgen’s recombinant G-CSF was biologically active by using an assay  
(a scientific test) known as the WEHI-3B (D+) assay [the WEHI Assay]. This assay tested the  
ability of a protein to induce differentiation of WEHI-3B (D+) leukemic cells into mature  
granulocytes, a known and unique property of human G-CSF.  
[147] Dr. Griffin explains that the ability to differentiate WEHI-3B (D+) cells had been shown  
by the WEHI lab to be a distinguishing property of CSF-β (not shared by the other CSF produced  
by 5637 cells, CSF-α). In this way, the WEHI Assay allowed the Souza team to confirm the  
gene they cloned was the “pluripotent CSF” of Dr. Welte. Drs. Welte and Souza went on shortly  
thereafter to fully characterize all the biological activities of Amgen’s recombinant G-CSF, but  
the WEHI Assay was instrumental in initially confirming that this recombinant G-CSF was the  
analog to Dr. Welte’s naturally occurring factor.  
4. Mandate 4 - Meaning of “Pluripotent” in the 537 Patent  
[148] Amgen’s counsel then asked Dr. Griffin how the Skilled Person would have understood  
the term “pluripotent” or the acronym “hpG-CSF” throughout the 537 Patent when it was  
published on July 31, 2007. He opines the Skilled Person would have understood these  
references as that term was used at the time the 537 Patent was written, i.e., as describing a  
manufactured, recombinant version of the naturally occurring protein previously described in  
Welte 1985 as “pluripotent CSF”. In other words, the 537 Patent used that term to maintain  
continuity with the naming convention established in Welte 1985.  
Page: 57  
5. Mandate 5 - Contribution to the Field of Hematology  
[149] Asked to describe the impact of recombinant G-CSF on the field of hematology and  
oncology, Dr. Griffin explains that recombinant G-CSF, once purified, was quickly put into  
clinical use to fill an urgent need. It ultimately became the drug filgrastim, which revolutionized  
the treatment of cancer and has prevented deaths caused by infections due to neutropenia (a side  
effect of chemotherapy caused by its effect on hematopoiesis). When administered after  
chemotherapy, filgrastim typically shortens or eliminates levels of neutropenia and significantly  
reduces the risk of serious bacterial infections.  
6. General Observations on Reliability  
[150] In cross-examination, Pfizer elicited from Dr. Griffin the acknowledgement that, in 1991,  
he provided a series of declarations [the Declarations] in a proceeding before the US Patent and  
Trademarks Office [USPTO proceeding], in which he considered the 959 Application and Dr.  
Welte’s purification work. Neither these Declarations nor his participation in the USPTO  
proceeding are mentioned in Dr. Griffin’s report.  
[151] Pfizer argues the Declarations are directly relevant to the issues in the present litigation  
and should have been disclosed under the Code of Conduct for Expert Witnesses [the Code of  
Conduct] prescribed by the Federal Courts Rules, SOR/98-106. Paragraph 3(k) of the Code of  
Conduct requires disclosure of particulars of any aspect of the expert’s relationship with a party  
to the proceeding or the subject matter of his or her proposed evidence that might affect his or  
her duty to the Court. Pfizer also advances arguments as to the substance of those Declarations,  
which arguments will be considered later in these Reasons.  
Page: 58  
[152] Pfizer notes that the failure to provide disclosure, as required by the Code of Conduct,  
has been found to affect the weight to be given to expert evidence (see Kwicksutanaieuk Ah-  
Kwa-Mish First Nation v Attorney General of Canada, 2012 FC 517 at paras 69-70). While I  
accept this principle, I do not find it applicable in the present case. Dr. Griffin explained in cross-  
examination that his recollection of the Declarations (now 30 years old) was that the issues were  
perhaps overlapping but different. He did not see any way that his comments back then would  
stop him from entirely telling the truth and having his own faithful opinions today. My  
impression of Dr. Griffin’s overall testimony is that he answered questions directly and honestly,  
and I found him to be credible. I similarly accept his explanation surrounding the Declarations  
and do not find failure to disclose those documents to affect the weight due to his evidence.  
[153] With the above evidence and issues in mind, I turn to the Analysis portion of these  
reasons. I will first address Pfizer’s argument that the within action is an abuse of process in light  
of the Apotex Application, or that I should follow Justice Hughes’ factual and legal findings in  
the Apotex Decision because of judicial comity. Next, I will address Pfizer’s allegations of  
invalidity: (1) obviousness, (2) material misrepresentations; and (3) insufficiency. Finally, I will  
address Pfizer’s affirmative defense that its activities fall under the prior use exception and are  
not infringement.  
[154] As a threshold issue in this action, Pfizer argues it is an abuse of process for Amgen to re-  
litigate factual and legal issues that were decided by Justice Hughes in the Apotex Decision. At  
an earlier stage in this proceeding, Pfizer presented a motion seeking dismissal of Amgen’s  
Page: 59  
action, on the basis that it was an abuse of process in light of the Apotex Decision, under s 6.08  
of the Regulations. Prothonotary Milczynski dismissed that motion, and the Federal Court of  
Appeal upheld her decision (see Amgen Inc v Pfizer Canada Inc, 2018 FC 1078; Pfizer Canada  
Inc v Amgen Inc, 2019 FCA 249 [Pfizer Canada]). However, relying significantly on its decision  
in Apotex Inc v Pfizer Ireland Pharmaceuticals, 2011 FCA 77 [Pfizer Ireland], the Federal Court  
of Appeal held Pfizer was not precluded from raising the abuse of process doctrine at trial in  
connection with individual factual and legal findings in the Apotex Decision:  
[83] The Court’s decision in Pfizer Ireland leaves no doubt, in  
my respectful opinion, that the commencement of a section 55  
action cannot be prevented by reason of a decision made under  
section 6 of the Former Regulations. Hence, I am satisfied that the  
same conclusion must be reached in respect of an action  
commenced under section 6 of the Amended Regulations which,  
for all intents and purposes, is a proceeding identical to a section  
55 action.  
[84] Thus, although Pfizer cannot succeed on the motion now  
before this Court, it remains open to it to raise issue estoppel and  
abuse of process once Amgen’s action goes to trial. Whether or not  
Pfizer can succeed on those grounds in respect of factual findings  
and legal determinations made by the Hughes Decision, shall, as  
Sexton J.A. made clear in Pfizer Ireland, depend on the trial  
judge’s assessment of these issues in light of the evidence.  
[155] Pfizer identifies several findings by Justice Hughes that it argues would represent an  
abuse of process to re-litigate;  
A. Dr. Welte had already identified the critical protein, isolated it, purified it, and  
characterized it in several respects;  
B. Welte 1985 was motivational for leading edge scientific labs such as Amgen  
to undertake the task laid out by Dr. Welte;  
C. Dr. Welte found the protein and said to the readers of his paper to go out and  
make it in quantity, which Amgen did;  
Page: 60  
D. Amgen obtained a product having an amino acid sequence beginning with a  
methionine, the addition of which was simply part of the process necessary in  
order to create the recombinant protein that Dr. Welte said should be made;  
E. Amgen’s steps in carrying out the G-CSF project were routine in the sense  
that they were carried out by skilled persons operating with the science as it  
was known at the time;  
F. Amgen did not utilize any hitherto unknown step or technique; and  
G. Amgen’s end product, which is simply the protein made by whatever process,  
was not itself inventive.  
[156] As explained in Pfizer Canada at paragraph 57, the principles informing an abuse of  
process analysis were identified by the Supreme Court of Canada in Toronto (City) v CUPE,  
Local 79, 2003 SCC 63, and include the need to address attempts to re-litigate a claim already  
determined by the Court that would have a negative impact on judicial economy, consistency,  
finality, and the integrity of the administration of justice.  
[157] Pfizer Ireland explains the application of these principles to the interaction between NOC  
applications and subsequent infringement actions (at paras 24-25 [emphasis added]):  
[24] This court has repeatedly said that NOC proceedings are  
quite different from subsequent infringement or impeachment  
actions. In my view, there is scope for applying the bars of issue  
estoppel and abuse of process in the later proceedings to prevent  
the relitigation of subsidiary factual and legal issues in order to  
preserve judicial resources, promote the integrity of the justice  
system, prevent inconsistent findings, and prevent abuse. The  
difference between the NOC proceeding and later proceedings is  
an important consideration for the judge in the later proceedings,  
along with all of the other discretionary considerations discussed in  
Danyluk and C.U.P.E. Simply put, Danyluk and C.U.P.E. can  
apply in proceedings such as these.  
[25] Given the foregoing analysis to the effect that res judicata  
does not apply to the determination of validity and infringement,  
Page: 61  
the parties remain free to launch proceedings on those issues in  
other fora. Where a party introduces significant and important new  
evidence or raises significant and important new argumentation in  
the subsequent action, the trial judge should reconsider the issue in  
light of the full record before him or her (Ratiopharm at  
paragraphs 25 and 26). In applying the rule that issue estoppel  
generally precludes parties from raising arguments or issues that  
could have been raised at the original hearing, courts should be  
cognisant of the summary nature of NOC proceedings and the fact  
that no discoveries or live evidence are permissible.  
[158] Noting the language highlighted above, Pfizer argues that Amgen bears a burden to lead  
evidence capable of unseating the findings from the Apotex Decision and that it has failed to  
discharge that burden. Pfizer submits that all Amgen’s fact witnesses in this case were heard by  
Justice Hughes and that, while two of Amgen’s three experts are new, none points to any step  
taken by Amgen that was not described in the prior art.  
[159] Amgen disputes that it bears a burden as articulated by Pfizer. Instead, it reads the same  
language in Pfizer Ireland as describing one scenario in which the trial judge should reconsider  
the issues in light of the full record. That is, the introduction of significant new evidence is not  
the only circumstance in which the trial judge should do so. To support its position that the Court  
should reconsider the issues upon which Justice Hughes has already pronounced, Amgen argues  
Justice Hughes erred in his legal analysis of obviousness for Claim 43. It notes there has been no  
substantive appellate consideration of such alleged errors, as the Federal Court of Appeal  
dismissed Amgen’s appeal of the Apotex Decision on the basis of mootness (see Amgen Canada  
Inc v Apotex Inc, 2016 FCA 196 [Amgen Canada]).  
Page: 62  
[160] I do not consider it this Court’s role, when assessing abuse of process submissions, to  
consider whether another decision of this Court demonstrates legal error (see MacDougall v Lake  
Country (District), 2012 BCCA 408 [MacDougall] at para 36, for a similar conclusion in the  
context of res judicata). However, the fact that Amgen has not had an opportunity to subject  
those alleged errors to appellate review is relevant to my discretion whether to apply the  
principle of abuse of process.  
[161] Pfizer Ireland notes (at para 24) that the difference between the NOC proceeding and  
later proceedings is an important consideration, along with all of the other considerations  
discussed in the applicable Supreme Court jurisprudence, in exercising this discretion. The  
unavailability of appellate review of the NOC decision forms part of this important  
consideration. In Penner v Niagara Regional Police Services Board, 2013 SCC 19 [Penner] at  
paragraph 41, the Supreme Court identified the availability of an appeal as an important  
consideration in an issue estoppel analysis. In the absence of an opportunity to have an earlier  
decision reviewed, it may be unfair to hold a party to the results of that decision for purposes of  
later proceedings. I find this factor similarly relevant to an abuse of process analysis.  
[162] I note Penner provides this guidance in the context of an earlier decision by an  
administrative decision-maker. Pfizer refers to jurisprudence to the effect that, when the earlier  
decision is from a court (as opposed to a tribunal), the discretion to decline to apply the abuse of  
process doctrine is limited in its application (see Procter & Gamble Pharmaceuticals Canada  
Inc v Canada (Minister of Health), 2003 FCA 467 [Proctor] at paras 28-29; MacDougall at para  
Page: 63  
[163] However, I do not read these authorities as suggesting that the inability to appeal an  
earlier decision, even a decision of a court, cannot be a circumstance where the applicable  
discretion is available. In deciding to apply the doctrine of issue estoppel in relation to a decision  
of a court of competent jurisdiction, the British Columbia Court of Appeal in MacDougall took  
into account the fact that there was an available right of appeal, which simply had not been  
exercised (at para 35). Indeed, in Assiniboine v Meeches, 2013 FCA 177 at paragraph 37, the  
Federal Court of Appeal noted that the comments at paragraphs 40-41 of Penner were made in the  
context of a claim of issue estoppel following an administrative decision, but the Court held they  
were nevertheless applicable to that case, which involved decisions of the Federal Court.  
[164] In my view, it is unfair to hold Amgen to the results of the Apotex Decision in the current  
proceedings, when it did not have the benefit of substantive appellate review of that decision. As  
Amgen emphasizes, the Federal Court of Appeal in Amgen Canada dismissed Amgen’s appeal  
for mootness in part because it could pursue a subsequent infringement action (at para 22). In  
conclusion on this issue, regardless of the scope of Amgen’s burden to identify evidence  
warranting reconsideration of the issues before Justice Hughes, I have decided to exercise my  
discretion not to apply the abuse of process doctrine and will therefore address the issues in this  
action on their merits.  
[165] In in its opening written submissions, Pfizer argued the Court should defer to the Apotex  
Decision by reason of judicial comity, even if I decide I am not bound by that decision as a  
Page: 64  
matter of abuse of process. As Pfizer did not pursue this argument in its closing submissions, I  
will address it only briefly.  
[166] Pfizer refers to Allergan Inc v Canada (Minister of Health), 2012 FCA 308 [Allergan] at  
paragraph 50, in which the Federal Court of Appeal held the Federal Court should have applied  
principles of comity and adhered to findings of law in another Federal Court decision, involving  
the same patent but different parties. To similar effect, in Apotex Inc v Pfizer Canada Inc, 2013  
FC 493 at paragraph 18, Justice O’Reilly held an earlier decision by Justice Snider as to the  
construction of the same patent was binding on him unless it was, for strong reasons, necessary  
to depart from it.  
[167] I accept the importance of stare decisis and its cousin, judicial comity. However, the  
authorities upon which Pfizer relies apply these principles to prior findings of law, not to  
findings of fact or mixed law and fact. Indeed, in Allergan, the Federal Court of Appeal notes the  
doctrine of comity has no application with respect to findings of fact (at para 50). As Justice  
Fothergill explained in Bayer Inc v Apotex Inc, 2016 FC 1013 [Bayer] at para 54, in the context  
of an action for patent infringement following an earlier NOC decision:  
[54] Previous findings of fact or mixed fact and law made in the  
NOC context are potentially persuasive, but they must be  
approached with caution. For example, Justice Hughes previously  
defined the “person of ordinary skill in the art” […] in the NOC  
proceedings, but this is a question of mixed fact and law. It must  
therefore be determined anew based upon the evidence adduced in  
these proceedings. Obviousness is generally considered to be a  
question of fact or mixed fact and law, to which the principle of  
comity does not apply (Wenzel Downhole Tools Ltd v National-  
Oilwell Canada Ltd, 2012 FCA 333 at para 44 [Wenzel]; Allergan  
at para 44). The same holds true for the issues of ambiguity,  
overbreadth, utility, and insufficiency.  
Page: 65  
[168] The findings in the Apotex Decision that Pfizer argues would represent an abuse of  
process to re-litigate are all findings of either fact or mixed law and fact. The only finding of law  
that could be relevant to the present action is Justice Hughes’ construction of Claim 43.  
However, even that finding was a function of the particular evidence adduced in that application.  
Moreover, claim construction is not one of the findings Pfizer ask the Court to adopt. Rather, as  
will be explained in more detail below, the parties are largely agreed on the issue of claim  
construction in the present action. As such, I find good reason not to adopt the claim construction  
from the Apotex Decision (see Bayer at paras 52-53).  
[169] With respect to questions involving findings of fact and mixed fact and law, I recognize  
they are potentially persuasive (see Bayer at para 54), and I will therefore afford them respectful  
attention. However, those questions must be answered based upon the evidence adduced in the  
present action.  
[170] Although the parties largely agree on the construction of the Asserted Claims, the task of  
claim construction rests with the Court (see, e.g., Zero Spill Systems (Int’I) Inc v Heide, 2015  
FCA 115 at paragraph 41).  
[171] Analytically, claim construction first requires identifying the Skilled Person to whom the  
patent and its claims are addressed. In general, the qualities and capabilities of the Skilled Person  
are the same for purposes of construing the patent and for the assessment of obviousness that will  
Page: 66  
be required later in these Reasons (see Leo Pharma Inc v Teva Canada Limited, 2015 FC 1237 at  
para 103 [Leo Pharma]).  
[172] The Skilled Person is a hypothetical person possessing the ordinary skill and knowledge  
of the particular art to which the invention relates and a mind willing to understand a  
specification that is addressed to them (see, e.g., Tetra Tech EBA Inc v Georgetown Rail  
Equipment Company, 2019 FCA 203 at para 25, citing Free World Trust v Électro Santé Inc,  
2000 SCC 66 [Free World Trust] at para 44). The Skilled Person is understood to be a technician  
skilled in the art but having no scintilla of inventiveness or imagination; a paragon of deduction  
and dexterity, wholly devoid of intuition; a triumph of the left hemisphere over the right (see  
Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61 [Plavix] at para 52). The Skilled  
Person may be conceived of as a team of people possessed of different skills (see Teva Canada  
Limited v Jansen Inc, 2018 FC 754 at para 66).  
[173] There is no material dispute over the areas in which the Skilled Person in this case must  
be qualified. All experts performed their analyses using the definition supplied by Dr. Van Etten:  
a team consisting of a molecular biologist with a PhD and several years of work experience in  
academia or industry; a hematologist with an MD and board certification (or, alternatively, a  
PhD in hematology and several years of work experience in academia or industry); and a protein  
biochemist with a PhD and several years of work experience in academia or industry.  
[174] I note that Amgen's experts opined that the Skilled Person might be less experienced than  
suggested by the definition supplied by Dr. Van Etten. Nevertheless, they were instructed to use  
Page: 67  
Dr. Van Etten’s definition for purposes of their analyses and do not conduct distinct analyses  
from the perspective of a Skilled Person with less experience. I am also mindful that Amgen’s  
expert Dr. Maloy opined the Skilled Person would not necessarily have had the technical skills or  
equipment required to put the teachings of the 537 Patent into action. This characterization is  
inconsistent with the legal requirement that the Skilled Person is able to practice the invention  
disclosed in the patent (see, e.g., Pfizer Canada Inc v Novopharm Ltd, 2012 SCC 60 at para 71  
[Novopharm SCC]). Taking that principle into account, as well as Amgen’s general adoption of  
Dr. Van Etten’s definition, I prefer Dr. Van Etten’s definition of the Skilled Person and adopt it  
for purposes of these Reasons.  
[175] Having identified the Skilled Person, I must determine how the Skilled Person would  
construe the Asserted Claims of the 537 Patent. As explained below, there is no material  
disagreement between the parties on this issue. As such, I need not comment in any detail on the  
expert evidence, other than to confirm that I consider the evidence to support the constructions I  
adopt below.  
[176] While they are all independent claims, Claims 44 to 47 all build upon Claim 43, and  
specifically the Claim 43 amino acid sequence. Amgen’s and Pfizer’s proposed constructions of  
Claim 43 are as follows:  
A. Amgen: Claim 43 pertains to a polypeptide with the specified sequence of  
175 amino acids.  
Page: 68  
B. Pfizer: Claim 43 pertains to a polypeptide with a specified sequence of 175