AbbVie Corporation v. Jamp Pharma Corporation

AbbVie Corporation v. Jamp Pharma Corporation
Court (s) Database
Federal Court Decisions
Date
2023-12-04
Neutral citation
2023 FC 1520
File numbers
T-557-21, T-561-21, T-573-21, T-577-21
Decision Content
Date: 20231204
Dockets: T-557-21
T-561-21
T-573-21
T-577-21
Citation: 2023 FC 1520
Ottawa, Ontario, December 4, 2023
PRESENT: The Honourable Madam Justice McVeigh
Docket: T-557-21
BETWEEN:
ABBVIE CORPORATION AND ABBVIE BIOTECHNOLOGY LTD
Plaintiffs
and
JAMP PHARMA CORPORATION
Defendant
Docket: T-561-21
AND BETWEEN:
ABBVIE CORPORATION AND ABBVIE BIOTECHNOLOGY LTD
Plaintiffs
and
JAMP PHARMA CORPORATION
Defendant
Docket: T-573-21
AND BETWEEN:
JAMP PHARMA CORPORATION
Plaintiff by Counterclaim
and
ABBVIE CORPORATION AND ABBVIE BIOTECHNOLOGY LTD
Defendants by Counterclaim
Docket: T-577-21
AND BETWEEN:
JAMP PHARMA CORPORATION
Plaintiff by Counterclaim
and
ABBVIE CORPORATION AND ABBVIE BIOTECHNOLOGY LTD
Defendants by Counterclaim
PUBLIC JUDGMENT AND REASONS (Confidential version issued on November 16, 2023)
I. Overview [1] This matter involves a dispute between JAMP Pharma Corporation (“JAMP”) and AbbVie Corporation and AbbVie Biotechnology Ltd (collectively, “AbbVie”). This dispute relates to JAMP’s SIMLANDI product – a biosimilar of AbbVie’s HUMIRA.
[2] HUMIRA is a successful and well-known drug, which purports to have changed the lives of millions of patients. HUMIRA is the brand name for the monoclonal antibody (“mAb”) adalimumab sold by AbbVie and is used to treat a range of autoimmune disorders, including rheumatoid arthritis, Crohn's disease, and hidradenitis suppurativa (“HS”), amongst many other diseases.
[3] There are three patents at issue in this matter, all of which pertain to AbbVie’s HUMIRA: Canadian Patent No 2,504,868 (the “868 Patent”); Canadian Patent No 2,801,917 (the “917 Patent”); and Canadian Patent No 2,904,458 (the “458 Patent”). Adalimumab is the anti-inflammatory biologic that is contained in each of the claimed patent inventions in this matter.
[4] This proceeding involves two patent infringement actions and two impeachment actions pursuant to subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 [the Regulations], subsections 60(1)-(2) and 55(1) of the Patent Act, RSC 1985, c P-4 [the Patent Act] [Appendix A].
[5] Ultimately, this matter largely comes down to legal conceptual differences, as opposed to vast disagreements with the evidence. I commend the parties for distilling the issues down with appropriate concessions.
[6] For the reasons that follow, I find that JAMP has established on a balance of probabilities that the asserted claims of the 868 and 917 Patents are invalid. In light of the prior art, I find the dosing regimens for the 868 and 917 Patents were obvious to try.
[7] However, I find that JAMP has failed to demonstrate that the asserted claims of the 458 Patent are invalid. Those claims are not anticipated by WO 2006/138181 (the “181 Application”), nor are they obvious to try in light of the prior art. I also do not find the asserted claims are invalid due to overbreadth or double patenting.
[8] JAMP has conceded infringement of the 458 Patent. However, I will not grant AbbVie the injunction they sought, which would have restrained JAMP from making, using, promoting, or selling SIMLANDI in Canada until the 458 Patent expires on November 28, 2028. I also will not grant AbbVie’s request for delivery up or destruction of the infringing products.
II. Background [9] Court File T-557-21 involves one of the two patent infringement actions pursuant to subsection 6(1) of the Regulations [Appendix A]. In that action, AbbVie alleges JAMP directly or indirectly infringes the 868 Patent and the 917 Patent. JAMP denies infringement of the patents and counterclaims, pleading the patents and their claims are invalid pursuant to section 60 of the Patent Act and section 8.1 of the Regulations [Appendix A].
[10] Court File T-573-21 involves a patent impeachment action, where JAMP seeks declarations of invalidity with respect to each of the patents and the claims at issue pursuant to subsection 60(1) of the Patent Act [Appendix A]. For each of the patents, JAMP seeks declarations pursuant to subsection 60(2) of the Patent Act that the making, using, or selling of JAMP products by JAMP in Canada will not infringe any of the valid asserted claims of the three patents at issue. AbbVie counterclaims pursuant to the Patent Act, seeking declarations that the claims of the 868 Patent and the 917 Patent are valid.
[11] Court File T-561-21 pertains to the 458 Patent and is the second infringement action pursuant to the Regulations. In that action, AbbVie seeks a declaration pursuant to subsection 6(1) of the Regulations [Appendix A] that the making, constructing, using, or selling by JAMP of its SIMLANDI product would directly or indirectly infringe the asserted claims of the 458 Patent. JAMP counterclaims, requesting a declaration that the asserted 458 Patent claims are invalid pursuant to section 60 of the Patent Act and section 8.1 of the Regulations [Appendix A].
[12] Court File T-577-21 relates to the 458 Patent and is the second impeachment action pursuant to subsection 60 of the Patent Act [Appendix A]. There, JAMP seeks a declaration of invalidity pursuant to subsection 60(1) of the Patent Act [Appendix A]. JAMP also seeks a declaration pursuant to subsection 60(2) of the Patent Act that the making, using, or selling of JAMP products by JAMP in Canada will not infringe any of the valid asserted claims of the 458 Patent. AbbVie counterclaims, asking for a declaration that the 458 Patent and its claims are valid and will be infringed by JAMP’s SIMLANDI product, pleading the Patent Act.
A. The Parties [13] AbbVie Corporation is a corporation existing under the laws of the province of Québec, having a principal office or place of business at 8401 Trans-Canada Highway in Montreal. AbbVie Biotechnology Ltd is a corporation existing under the laws of Bermuda with a principal office or place of business in Hamilton, Bermuda.
[14] In 2013, Abbott Laboratories (“Abbott”) created AbbVie, which is an independent research-based pharmaceutical company.
[15] JAMP is a pharmaceutical company headquartered in Québec, and has its principal corporate office located at 1310 Nobel Street in Boucherville. JAMP operates its business as a manufacturer and distributor of pharmaceutical products.
B. Procedural History [16] In December 2020 or January 2021, JAMP sought regulatory approval in Canada for SIMLANDI in the 40mg/0.4 mL pre-filled syringe, 40 mg/0.4mL auto-injector pen, and 80mg/0.8mL pre-filled syringe (see Table below). On February 19, 2021, JAMP served a Notice of Allegation (“NOA”) on AbbVie pursuant to subsection 5(3) of the Regulations.
JAMP Presentation
Reference Biologic Drug
SIMLANDI, adalimumab, 40 mg in 0.4 mL sterile solution (100 mg/mL), subcutaneous injection, pre-filled syringe
HUMIRA, adalimumab, DIN 02458349, 40 mg in 0.4 mL sterile solution (100 mg/mL), subcutaneous injection, pre-filled syringe
SIMLANDI, adalimumab, 40 mg in 0.4 mL sterile solution (100 mg/mL), subcutaneous injection, auto-injector
HUMIRA, adalimumab, DIN 02458357, 40 mg in 0.4 mL sterile solution (100 mg/mL), subcutaneous injection, pre-filled pen
SIMLANDI, adalimumab, 80 mg in 0.8 mL sterile solution (100 mg/mL), subcutaneous injection, pre-filled syringe
HUMIRA, adalimumab, DIN 02466872, 80 mg in 0.8 mL sterile solution (100 mg/mL), subcutaneous injection, pre-filled syringe
[17] On January 5, 2022, the Minister of Health issued a Notice of Compliance (“NOC”) to JAMP for the three JAMP presentations.
[18] Accordingly, JAMP launched its products on April 13, 2022, under the brand name SIMLANDI.
[19] AbbVie judicially reviewed the Minister of Health’s decision to issue the NOC to JAMP, alleging the Minister erred by finding that JAMP was not a “second person” for the purposes of subsection 5(1) of the Regulations [Appendix A]. In AbbVie Corporation v Canada (Health), 2022 FC 1209 [AbbVie 2022], the Court found the Minister’s decision reasonable and dismissed the judicial review. An appeal is underway of that decision. At the time of writing this decision, the Federal Court of Appeal has yet to hear the appeal. This issue was not raised during the trial.
[20] Accordingly, following the trial, I issued a direction to the parties asking whether they wanted this Court to wait to release its decision, until after the Federal Court of Appeal determines the appeal, or whether I can proceed without regard to that decision.
[21] The parties jointly explained that the impeachment actions are “entirely unaffected” by the Federal Court of Appeal’s pending decision and that this decision can be released without regard to the appeal of AbbVie 2022. Therefore, at the time of the release of this decision, T-557-21 and T-561-21 are not at issue.
[22] A brief summary of the actions is provided below. The bolded box (first two lines) indicates those actions are not live in this decision.
Court File No.
Patents at Issue
Type of Action
T-557-21
868 and 917 Patents
PM(NOC) Action
T-561-21
458 Patent
PM(NOC) Action
T-573-21
868 and 917 Patents
Impeachment Action
T-577-21
458 Patent
Impeachment Action
[23] On March 1, 2022, the Case Management Judge bifurcated the liability determination from the quantification and specific damages assessment.
[24] At the outset of the trial, the parties advised the Court that they had agreed to withdraw all claims and counterclaims in respect of the remaining non-asserted claims of the 917 Patent and the 458 Patent. The parties withdrew all claims from Patent 2,847,142 (the “142 Patent”), Patent 2,385,745 (the “745 Patent”), and Patent 2,898,009 (the “009 Patent”). Accordingly, four court files associated with the 745 Patent and the 009 Patent are also no longer at issue.
[25] Finally, there is a confidentiality order presently in place that protects both parties’ confidential technical, scientific, regulatory, sales, marketing, financial, business strategy, and other commercially sensitive information (or proprietary information) not otherwise known or available to the public.
C. Technical Background (1) HUMIRA and Adalimumab [26] D2E7, adalimumab, was the first fully human mAb developed in the world (Dr. Hoffman Witness Statement at para 28). It is not disputed that adalimumab and HUMIRA were a breakthrough for the treatment of rheumatoid arthritis. HUMIRA stands for “human monoclonal antibody in rheumatoid arthritis”.
[27] HUMIRA was initially approved for patients with rheumatoid arthritis. The original buffered adalimumab formulation of HUMIRA was approved by the Food and Drug Administration (“FDA”) in 2002. In Canada, HUMIRA first received approval in 2004 as a 50 mg/mL concentration of adalimumab. Amongst many other indications, HUMIRA is widely used around the world to treat rheumatoid arthritis, adult and pediatric Crohn’s disease, and psoriasis: AbbVie 2022 at para 15. AbbVie is the exclusive marketer and seller of HUMIRA in Canada.
[28] Currently, AbbVie Corporation is authorized to market and sell the drug HUMIRA in Canada in the following strengths:
HUMIRA Strength
Approval
40 mg/0.8 mL sterile solution (50 mg/mL)
NOC on September 24, 2004
10 mg/0.1 mL sterile solution (100 mg/mL)
NOC on March 26, 2018
20 mg/0.2 mL sterile solution (100 mg/mL)
NOC on March 26, 2018
40 mg/0.4 mL sterile solution (100 mg/mL)
NOC on October 13, 2016
80 mg/0.8 mL sterile solution (100 mg/mL)
NOC July 28, 2017 and March 26, 2018
[29] Inflammation is the body’s immune response, which generally protects the body from disease and fights infection. Typically, the body will respond to threats by triggering an immune response to eliminate the threats. However, in some diseases, the immune system targets the body’s own cells and tissues (Dr. Marshall October Report at para 29). Cytokines are proteins that communicate between cells and assist in triggering an immune response. Tumor necrosis factor alpha (“TNFα”) identifies threats and triggers the immune response to clear threats from the body (Dr. Marshall October Report at para 30).
[30] Antibodies are another type of protein that is also involved in the body’s immune response to threats. Antibodies respond to a specific antigen and bind to the antigen to neutralize it. Antibodies consist of two parts: 1) the antigen-binding region and 2) the constant region (Dr. Marshall October Report at para 33).
[31] Antibody therapies function by targeting specific proteins in the body and neutralizing undesired side effects of the proteins (Dr. Marshall October Report at para 54). Adalimumab, also known as D2E7, binds to soluble TNFα and neutralizes the biological function of tumor necrosis factor (“TNF”) by blocking its interaction with cell surface TNF receptors. HUMIRA is a biologic therapy, meaning it is a protein-based drug that is derived from cells or living organisms (Dr. Marshall October Report at para 54).
[32] Throughout the trial, there were discussions about human anti-human antibodies (“HAHAs”), which are now better known as anti-drug antibodies (“ADAs”). HAHAs and ADAs are produced by the body in response to humanized monoclonal antibodies (“mAbs”), and are a form of immunogenicity. The production of ADAs has the potential to impact adalimumab effectiveness in patients. When developing use of a new mAb, there is frequently concern about minimizing the development of ADAs. In and around 2004, ADAs had previously been reported for TNFα inhibitors. For example, the REMICADE (infliximab) Package Insert warned of ADAs and the associated risk of infusion related reactions (Dr. Mould Responding Report at para 91).
(a) Protein Stability [33] A key consideration in mAb formulation is the stability of the protein formulation. This involves numerous considerations, including the potential of hydrogen (“pH”), conductivity, buffering agents, excipients, and the structure of the protein itself.
[34] Immunoglobulin G (“IgG”) antibodies have a general Y structure, consisting of two light chains and two heavy chains. The amino acid sequence for IgG antibodies are similar (Dr. Falconer Report at paras 93-96 and Dr. Falconer’s PowerPoint at slide 6).
[35] Proteins can vary dramatically and unpredictably, even when they have similar structures (Dr. Trout’s PowerPoint at slide 12). There are two classes of instability that can negatively impact the efficacy, safety, or appearance of the protein formulation: chemical and physical instability. Chemical instability leads to modification of the protein through bond formation or cleavage, which is where the peptide bonds between the amino acids essentially break. Physical instability involves changes to the “higher order structure of the protein” (458 Patent at 1).
[36] Pharmaceutical formulation scientists attempt to overcome these instabilities through the formulation process. The formulation of the protein is important, as the protein concentration increases, so does aggregation, insolubility, and degradation of the protein (458 Patent at 3 and Dr. Trout July Report at para 52).
[37] Aggregation results when the mAb molecules self-associate, which also potentially leads to mAb precipitates.
[38] pH is an important consideration, as the solubility, physical, and chemical stability of mAbs is pH dependent (Dr. Falconer’s PowerPoint at slide 11). Any given mAb formulation will have a pH value. The isoelectric point (or “pI value”), is where the pH of a formulation will have a neutral charge (Dr. Falconer’s PowerPoint at slide 11). The further away the pH value is from the mAb’s pI value, the more charged the molecules are. This means that the molecules repel each other, which increases solubility and decreases viscosity (Dr. Falconer’s PowerPoint at slide 11).
[39] Excipients are used to maintain the given pH of a formulation. Buffering systems are an example of an excipient that can be added to a protein formulation.
[40] Buffering systems can be used to stabilize aqueous protein formulations, as buffers help maintain the pH of the formulation. There is an array of buffers such as acetate, succinate, citrate, amino acids, and phosphate (Dr. Falconer’s PowerPoint at slide 13). Buffers have their own buffering capacity, which increases proportionally with the increasing buffer concentration, and a certain buffer range (Dr. Falconer’s PowerPoint at slide 13).
[41] Surfactants are used in protein formulation as they reduce surface tension and decrease the driving force for protein adsorption, as well as aggregation on hydrophobic surfaces (Dr. Falconer’s PowerPoint at slide 18).
[42] All of these considerations are important when creating and manufacturing mAbs because aggregation, insolubility, and degradation have implications on drug safety and efficiency.
(b) PK/PD Modelling [43] Pharmacokinetic (“PK”) is a branch within pharmacology that attempts to understand the effects of the body on an administered drug (Dr. Noertersheuser Witness Statement at para 1). PK models determine the fate of substances administered to a living organism. In essence, PK modelling understands what the body does to the drug (Dr. Mould’s PowerPoint at slide 4 and Dr. Mould Report at para 41). There are several different types of PK modelling, including individual PK modelling, population PK modelling, and meta-modelling. PK deals with absorption, distribution, metabolism, and excretion.
[44] Pharmacodynamics (“PD”) is another branch within pharmacology which analyzes the impact of a drug on the body. PD models simulate the biological response of the drug over time, following administration of a drug, thereby allowing a modeller to understand the body’s response to the drug.
[45] PK/PD modelling combines these two disciplines in one complex model. A PK/PD model translates biological data into a mathematical framework. The PK/PD model consists of a series of mathematical equations and functions which can be used to predict what the body may do to a drug upon administration and what the effects may be on the body (Dr. Noertersheuser Witness Statement at para 2). The model can be used to support the development of clinical trial protocols.
(2) Crohn’s Disease and Ulcerative Colitis [46] Crohn’s disease and ulcerative colitis (“UC”) are types of inflammatory bowel disease (“IBD”). Both are serious diseases that affect the gastrointestinal tract (“GI”) of the body.
[47] UC is confined to the colon and is characterized by inflammation of the colon, which causes diarrhea and bleeding. Discrete ulcers may be seen in the colon with UC, and the inflammation seen in UC is contiguous (Dr. Howden August Report at para 109).
[48] Unlike UC, Crohn’s disease can occur anywhere in the GI tract. Inflammation also occurs in Crohn’s disease, although the inflammation is typically patchier than UC. There may be “skip lesions” in persons affected with Crohn’s disease, meaning that while some areas of the GI tract can be actively affected, the inflamed areas can be separated by normal-appearing areas.
[49] A comparison of the location, inflammation, and symptoms of Crohn’s disease and UC can be seen below (Dr. Howden’s PowerPoint at slides 9 and 10):
Crohn’s Disease
Ulcerative Colitis
Location
Can occur anywhere in the GI tract
Confined to the colon (i.e. large intestine)
Inflammation
Inflammation …. more patchy than in UC “Skip lesions”
Inflammation …. is contiguous
Symptoms
Diarrhea and rectal bleeding Rectal bleeding not always present Obstruction or abscess formation Infections with intestinal abscess formation, fistulas, episodes of intestinal obstruction and … colorectal cancer Life-threatening and may require surgery
Diarrhea and rectal bleeding May or may not … discrete ulcers in the colon Anemia Toxic dilatation of the colon … a medical/surgical emergency If [medical treatment] fails …. surgical removal of the entire colon is required Long-term risk of colorectal cancer
(3) HS [50] HS is a skin disorder of the apocrine glands and hair follicles, which involves swollen, painful, chronically inflamed lesions or lumps that develop in the groin and sometimes under the breasts and armpits. HS has a horrible odor from “purulent, malodorurant fluid” (Dr. Okun Nov 17 page 660 line 21), and many witnesses testified this a very unpleasant symptom. This, along with other symptoms, causes a reduced quality of life for patients (Dr. Okun Nov 17 page 660 line 27). HS symptoms appear and disappear over time.
[51] HS frequently occurs in patients who have other medical conditions, such as acne, diabetes, IBD, and in patients who are overweight (Dr. Sauder Invalidity Report at para 65).
[52] HS exists with varying severity in patients, ranging from mild symptoms to severe. HS can range from the appearance of swollen pimple-like bumps on the skin to lesion or lumps infected by bacteria (such as abscesses or draining fistulas) that can lead to scarring (Dr. Sauder’s PowerPoint at slide 18 and Dr. Sauder Invalidity Report at para 63).
[53] Treatment depends on the severity of HS. Mild forms can be treated using warm compresses, topical antibacterial agents or washes, oral antibiotics, as well as anti-inflammatory agents (Dr. Sauder Invalidity Report at para 67). Moderate forms can be treated similarly, with corticosteroids to reduce swelling and retinoids. As well, although the parties raised an issue about TNFα inhibitors on cross-examination, based on a present understanding of treatment, I recognize this is another treatment option (Dr. Sauder Invalidity Report at para 67). Finally, severe forms of HS may require surgical intervention (Dr. Sauder Invalidity Report at para 67).
D. The Patents at Issue (1) The 868 Patent [54] The 868 Patent discloses a multi-variable dose method for treating TNFα disorders, including Crohn’s disease and psoriasis. The 868 Patent is listed on the Canadian Patent Registrar in respect of the drug HUMIRA.
[55] The 868 Patent is titled “Multiple-Variable Dose Regimen for Treating TNF-α Related Disorders”. The 868 Patent was issued on November 29, 2016, and its earliest prior date is April 9, 2004. Its filing date is April 11, 2005 and its publication date is September 29, 2005.
[56] The named inventors of the 868 Patent are Rebecca S. Hoffman (US), Elliot Keith Chartash (US), Lori K. Taylor (US), George Richard Granneman (US), and Philip Yan (US).
[57] The 868 Patent contains five claims. Those five claims are as follows:
868 Patent
Claims
1.
Use of D2E7 in multiple doses for treating inflammatory bowel disease in a human subject, wherein the multiple doses comprise of: a first dose of 160 mg of D2E7 for subcutaneous administration; a second dose of 80 mg of D2E7 for subcutaneous administration two weeks following administration of the first dose; and a third dose of 40 mg of D2E7 for subcutaneous administration two weeks following administration of the second dose.
2.
The use according to claim 1, additionally comprising further doses of 40 mg of D2E7 for subcutaneous administration two weeks apart commencing two weeks following administration of the third dose.
3.
The use according to claims 1 or 2, wherein the first dose and the second dose are provided in four and two dosage unit forms of 40 mg of D2E7 each, respectively.
4.
The use according to any one of claims 1 to 3, wherein the inflammatory bowel disease is Crohn's disease.
5.
The use according to any one of claims 1 to 3, wherein the inflammatory bowel disease is ulcerative colitis.
(2) The 917 Patent [58] The 917 Patent is directed to the treatment of HS. The 917 Patent is also listed on the Canadian Patent Registrar in respect of the drug HUMIRA.
[59] The 917 Patent is titled “Uses and Compositions for Treatment of Hidradenitis Suppurativa (HS)”. The earliest priority date of the 917 Patent is June 3, 2010 and its filing date is June 3, 2011. The 917 Patent’s publication date is December 8, 2011 and it was issued on April 25, 2017.
[60] The two named inventors of the 917 Patent are Martin M. Okun (US) and Thomas C. Harris (US).
[61] The 917 Patent consists of seven claims. Those seven claims are as follows:
917 Patent
Claims
1.
Use of adalimumab, in multiple doses for treating moderate to severe hidradenitis suppurativa (HS) in an adult, wherein the multiple doses comprise:
a first loading dose of 160 mg of adalimumab for subcutaneous administration to the subject at week 0;
a second loading dose of 80 mg of adalimumab for subcutaneous administration to the subject at week 2; and
a weekly maintenance dose of 40 mg of adalimumab for subcutaneous administration to the adult starting at week 4, wherein said multiple doses are not subject to any discretionary adjustment by a physician or medical practitioner.
2.
The use of claim 1, further comprising use of a biweekly maintenance dose of 40 mg of adalimumab for subcutaneous administration to the adult starting at week 16, wherein said weekly administration of the maintenance dose stops after week 15.
3.
The use of any one of claims 1 to 2 wherein said treating decreases the number of inflammatory lesions in the adult.
4.
The use of any one of claims 1 to 3 wherein said treating prevents worsening of abscesses in the adult
5.
The use of any one of claims 1 to 4 wherein said treating prevents worsening of draining fistulas in the adult.
6.
The use of any one of claims 1 to 5, further comprising use of antibiotics in the adult.
7.
The use of any one of claims 1 to 6, wherein the adult had an inadequate response to oral antibiotics prior to said treating.
(3) The 458 Patent [62] The 458 Patent is titled “Protein Formulations and Methods of Making Same”. The 458 Patent deals with protein formulation, protein stability, and the shelf-life of proteins. Specifically, it is directed towards the finding that proteins formulated in water maintain solubility, as well as stability, even at high concentrations, during long-term liquid storage or other processing steps (458 Patent at page 4). The 458 Patent reports that “the formulations of the invention do not rely on a buffering system and excipients, including surfactants, to keep proteins in the formulation soluble and from aggregating” (458 Patent at page 42).
[63] The 458 Patent consists of 280 claims. However, not all of the claims are at issue. Only the following claims are at issue in this matter [Appendix B]:
Claim 28 as it depends on claim 10 as it depends on claim 1;
Any one of claims 37, 38, 40-43, 45-49 and 215 that depend either directly or indirectly on claim 28;
Claim 83 as it depends on claim 72 as it depends on claim 69;
Any one of claims 75, 76, 78-80, 124, 125 and 215 that depend, either directly or indirectly, on claims 83, 72 or 69;
Claim 217 as it depends on claim 193 as it depends on claim 192 as it depends on claim 191; and
Any of claims 194-198, 204 and 205 that depend, either directly or indirectly, on claims 217, 193, 192 or 191.
E. SIMLANDI [64] JAMP markets its product SIMLANDI in Canada, which is a “biosimilar” of AbbVie’s HUMIRA. JAMP began selling SIMLANDI in Canada on April 13, 2022.
[65] SIMLANDI is available as a 40 mg/0.4 mL pre-filled syringe, 40 mg/0.4 mL pre-filled auto-injector, and 80 mg/0.8 mL pre-filled syringe. It is a high concentration, low volume, citrate-free formulation.
F. Witnesses-General Comments [66] Before turning to the specific witnesses for the parties, I wish to comment on the quality and calibre of the expert witnesses in this matter for all the patents at issue. All of the witnesses were excellent and provided assistance to the Court, subject to some observations. These specific concerns will be addressed when dealing with their evidence.
[67] Generally, the fact witnesses were candid and helpful. Some of the invention stories occurred a long time ago; therefore, this may be how the stories are remembered now. In the analysis, I will address any concerns that I need to by giving that testimony less weight or preferring another witness’s testimony on that particular matter.
[68] Counsel for AbbVie made much out of the opposing expert witnesses and devoted significant portions of closing to impugning their credibility. However, as counsel for JAMP put it, “[n]o one was perfect. They all have their warts. I think we should deal with the merits” (December 14 Trial Transcript at 2510). That is exactly what I intend to do in these reasons for both parties witnesses.
G. Witnesses for AbbVie (1) Fact Witnesses (a) Dr. Rebecca S. Hoffman [69] Dr. Hoffman worked for 18 years at Abbott (as it was called then) and is a named inventor of the 868 Patent. In May of 2001, she was an Associate Medical Director at Abbott. During her time at AbbVie, she was a Global Medical Director. By 2008, Dr. Hoffman was responsible for all the global clinical development programs for HUMIRA.
[70] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||| Dr. Hoffman was involved in the clinical studies that ultimately led to the creation of the 868 Patent and the 458 Patent.
[71] Dr. Hoffman stated that Abbott was considering using adalimumab to treat Crohn’s disease as early as January 2002 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| || ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
[72] Dr. Hoffman testified to the invention process |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(b) Dr. Peter Noertersheuser [73] Dr. Noertersheuser worked at AbbVie and its predecessor companies for almost three decades. In the late 1990s, he began to develop PK/PD modelling for adalimumab, which was used to support the development of clinical trial protocols. Dr. Noertersheuser spoke to the PK/PD modelling that Abbott conducted and developed. He explained that the field of PK and PD biologics was relatively new and modelling was important for designing protocols for clinical trials. His work was used in the design of many protocols and trials, including Crohn’s disease and HS.
(c) Dr. Martin Okun [74] Dr. Okun is a medical doctor and former employee of Abbott. He is a named inventor of the 917 Patent. He helped develop the clinical study that investigated the use of adalimumab for the treatment of HS. |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||| He discussed the life altering impact of using HUMIRA on HS patients that responded well.
(d) Dr. Wolfgang Fraunhofer [75] Dr. Fraunhofer was a fact witness who spoke to the invention story of the 458 Patent. He is a highly qualified doctor with expertise in pharmaceutical formulation. He holds a pharmaceutical degree from Regensburg University and obtained his PhD in Pharmaceutical Technology and Biopharmaceutics at Ludwig University in Munich.
[76] Dr. Fraunhofer was not qualified as an expert witness; however, he was able to speak extensively on the prior art and the scientific knowledge of adalimumab in the 2000s. This was especially so in light of his PhD thesis, which focused on pharmaceutical antibodies and the use of analytical techniques to investigate their stability.
[77] Dr. Fraunhofer’s testimony was wide-ranging and JAMP sought to use it in many places alongside that of AbbVie’s expert witnesses. I will not do so. As mentioned, Dr. Fraunhofer was a fact witness, not an expert witness. He was not instructed in the law of claim construction, nor was he given the definitions of a person of ordinary skill in the art (“POSITA”) or the common general knowledge. Moreover, his position as a research scientist working on adalimumab for AbbVie makes it questionable whether his opinions, absent instruction from counsel, would line up with those of a POSITA and reflect the common general knowledge at the relevant time.
(2) Expert Witnesses (a) Dr. John Marshall [78] Dr. Marshall is a Professor of Medicine, Director of the Division of Gastroenterology and a full member of the Farncombe Family Digestive Health Research Institute at McMaster University. Up until 2018, he was Head of Clinical Research for the Division of Gastroenterology and Chief of Service for Gastroenterology at Hamilton Health Sciences.
[79] Dr. Marshall holds a Bachelor of Science from Queen’s University and he received his Doctor of Medicine (“MD”) from Queen’s University in 1992. He also obtained a Master of Science in Clinical Epidemiology and Biostatistics from McMaster University in 2000. He has extensive experience with IBD, including prior work with clinical trials, care, and research. He also has lengthy involvement with numerous journals relating to gastroenterology.
[80] Dr. Marshall provided expert evidence via his testimonial evidence and two expert reports in this matter. He was qualified to give his expertise in the evaluation, treatment, and research of Crohn’s disease and UC, including the clinical use of TNFα inhibitors. His expertise also relates to the design and conduct of clinical trials, including biologic medicines related to Crohn’s disease and UC.
[81] Dr. Marshall provided expert evidence for the 868 Patent. Specifically, he addressed the POSITA and interpreted the patent claims as of September 26, 2005. He also gave his opinion on whether JAMP was influencing physicians and patients to choose SIMLANDI for the treatment of Crohn’s disease and UC.
(b) Dr. Diane R. Mould [82] Dr. Mould is a pharmacologist with expertise in pharmacokinetics and pharmacodynamics. She has modelled and developed dosing regimens in clinical trials. She received her PhD in Pharmaceutics and Pharmaceutical Chemistry from the Ohio State University College of Pharmacy in 1989. She is an Adjunct Professor at the College of Pharmacy at the University of Rhode Island, the College of Pharmacy at Ohio State University, and in the Pharmaceutics Department at the University of Florida. Dr. Mould also taught at the National Institutes of Health.
[83] Dr. Mould spent a decade working for major pharmaceutical and biopharmaceutical companies, including Hoffman-La Roche, Amgen, and SmithKline-Beecham. From 1999 to 2001, she worked for a consulting company, PharSight, on their scientific advisory board. In 2001, Dr. Mould founded Projections Research, Inc., which advises the pharmaceutical industry on pharmacology issues, including individual and population PK and PD models. Her models can be used to simulate different dose regimens and treatment options, design clinical studies, and support proposed labeling and dose adjustments. She has published a number of papers on the PK and PD of many of the currently approved mAb therapeutics, as well as other immunomodulatory biological agents.
[84] In this matter, Dr. Mould provided an expert report, along with a responding report to Dr. Sauder’s and Dr. Baughman’s expert reports. Her opinions related to the validity of the 868 Patent and the 917 Patent. Dr. Mould’s expertise also included dosing simulations for small molecule and biologic drugs.
[85] Her evidence described the POSITA for the 868 Patent, along with the common general knowledge as of April 9, 2004 (the priority date). She opined on the construction and validity of the 868 patent and responded to Dr. Baughman’s report. In her opinion, nothing in the prior art would have supported a pharmacologist selecting the dosing regimen for treating IBD of 160/80/40, given it was four times the approved dose for RA (Dr. Mould Responding Expert Report at paras 33 and 35). Dr. Mould stated there was a significant gap between the prior art and the inventive concept, and a pharmacologist would not have arrived at the 868 Patent claims.
[86] In her report, she also addressed the 917 Patent, including the POSITA and the common general knowledge as of June 3, 2010 (the priority date). Dr. Mould constructed the patent, reviewed its validity, and responded to Dr. Sauder’s report. In her opinion, there was a significant gap between the state of the art and the inventive concept of the 917 Patent claims, that the “use of adalimumab in the claimed 160/80/40 EW regimen is safe and effective to treat HS” (Dr. Mould Responding Expert Report at para 308). She opined that the skilled pharmacologist “would not have been led directly and without difficulty to the solution taught by the 917 Asserted Claims” (Dr. Mould Responding Expert Report at para 308).
(c) Dr. Gary Solomon [87] Dr. Solomon is an Associate Professor of Clinical Medicine at New York University Grossman School of Medicine. He obtained his Bachelor of Arts from the University of Michigan, and his MD from Mount Sinai School of Medicine in 1977. He has extensive experience in treating and researching inflammatory diseases, with a specific focus on treating inflammatory skin conditions. This rheumatology experience overlaps with the field of dermatology.
[88] Dr. Solomon provided two reports for the 917 Patent, including a response to Dr. Sauder’s Report. He provided opinions on the POSITA, the common general knowledge, and the construction of claims 1 and 3-5. His second expert report addressed whether the 917 claims would have been obvious, and whether the asserted claims constrained the ability of physicians to utilize their skill and judgment.
(d) Dr. Bernhardt Trout [89] Dr. Trout was AbbVie’s expert for the 458 Patent. He is the Raymond F. Baddour Professor of Chemical Engineering at Massachusetts Institute of Technology (“MIT”). He has previously taught courses and supervised students in the area of protein stability.
[90] Dr. Trout received his BS and MS degrees from MIT in 1990. He obtained a PhD in Chemical Engineering from the University of California at Berkley in 1996. He completed post-doctoral research at the Max Planck Institute for Solid State Physics in Stuttgart, Germany. Afterwards, Dr. Trout began his career as an Assistant Professor of Chemical Engineering at MIT. He became a full-time professor in 2008.
[91] Since 1998, Dr. Trout has conducted research at MIT in collaboration with the pharmaceutical industry. He has also worked with regulatory agencies, including the FDA. His research focuses on pharmaceutical development and manufacturing, including the stabilization and formulation of therapeutic proteins.
[92] From 2006 to 2014, Dr. Trout acted as the Co-Chair of the Chemical and Pharmaceutical Engineering Singapore-MIT Alliance Program. Additionally, from 2007 to 2019, Dr. Trout cofounded and served as the Director of the Novartis-MIT Centre for Continuous Manufacturing Research, which was aimed at transforming the way pharmaceuticals are manufactured.
[93] Dr. Trout has over 20 years of experience working on protein formulations and has focused his research on antibody formulation since 2004. Since joining MIT, Dr. Trout has w