2023 FC, 2023 FC 1520

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. 868 Patent Claims

(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 worked on approximately 50 biologic therapeutics, most of them being mAbs. [ 94 ] Dr.

Trout was qualified as an expert in the field of protein formulation, including formulations for mAbs, as well as protein stability and techniques used to assess their pharmaceutical formulations. Dr. Trout provided an expert report on claim construction and infringement for the 458 Patent. He also prepared a responding expert report on validity. [ 95 ] Dr. Trout provided evidence on the POSITA.

He opined the skilled person would be a team of persons with an educational background in the pharmaceutical sciences, chemical engineering, chemistry or related fields, having knowledge or experience with protein-based formulations. He also stated the educational degrees would be a PhD with one to two years of relevant experience in formulating protein-based compositions, or it could be a lesser degree, like a bachelors or masters but with proportional experience. [ 96 ] In his initial report, Dr. Trout provided his analysis of the claims at issue, detailing his

interpretation of claims 1 and 69, along with claim 191 (and those claims at issue dependent thereon). He also examined the issue of infringement, finding the making, importation, use, offer for sale, and sale of the product fell within the scope of the following claims of the 458 Patent: (

a) Claim 1 and the following claims which depend either directly or indirectly on Claim 1: Claim 10, Claim 28, Claim 37, Claim 38, Claims 40-43, Claims 45-49, and Claim 215. (

b) Claim 69 and the following claims which depend either directly or indirectly on Claim 69: Claim 72, Claim 75, Claim 76, Claims 78-80, Claim 83, Claim 124, Claim 125, and Claim 215. (

c) Claim 191 and the following claims which depend either directly or indirectly on Claim 191: Claims 192-198, Claim 204, Claim 205, and Claim 217. [ 97 ] Additionally, Dr. Trout provided his opinion on the two key validity issues: anticipation and obviousness. He stated the 181 Application neither disclosed nor enabled the subject matter of the 458 Patent. Dr. Trout found the 458 Patent was not obvious given the challenges associated with antibody formulation. In his responding report, Dr.

Trout noted antibody formulation is more difficult at high concentrations, since the formulation becomes more prone to stability issues as the concentration of antibodies increases. As of November 30, 2007, he stated it well known that a buffer was needed in a monoclonal antibody formulation to help stabilize the antibody formulation. Further, at that time, every commercially available monoclonal antibody formulation contained a buffer, including HUMIRA. (

e) Dr. Eduardo Mysler [ 98 ] Dr. Mysler is a physician and rheumatologist with experience in the clinical use of biologic medicines and biosimilars, including adalimumab biosimilars marketed in Argentina. His clinical practice focuses on treating rheumatologic diseases. He is also a research scientist and has published extensively on biosimilars, including on the safety and effectiveness of biosimilars and switching patients to or between biosimilars. [ 99 ] Dr.

Mysler obtained a medical degree in 1987 from the University of Buenos Aires and completed a fellowship in rheumatic disease at Cornell University from 1992 to 1995. He worked as a resident and an attending physician at the hospital for joint disease in New York City from 1996 to 1998. [ 100 ] Dr. Mysler explained how Health Canada has found each adalimumab biosimilar in the Canadian market is safe and effective, as

all of them have similar quality, safety and efficacy. Dr. Mysler opined there would be no harm to patients if SIMLANDI was removed from the market and patients were prescribed one of the other approved adalimumab biosimilars. Dr. Mysler explained how biosimilars in the European market are interchangeable and there have been no safety issues. (

f) Mr. Neil Palmer [ 101 ] Mr. Palmer did not provide testimonial evidence and his expert report was taken as read. Mr. Palmer gave evidence on drug approvals, specifically adalimumab biosimilars, and SIMLANDI’s market share in Canada. He was tendered as a pharmaceutical industry consultant with expertise in the Canadian marketplace; in particular, product pricing, market access, reimbursement policies, and interchangeability with the listing of drug products. H. Witnesses for JAMP

(1) Expert Witnesses (

a) Dr. Colin Howden [ 102 ] Dr. Howden is a doctor who specializes in gastroenterology. He presently treats patients with IBD, including Crohn’s disease and UC. He received his medical degree from the University of Glasgow in Scotland in 1978. [ 103 ] Dr. Howden was qualified as a gastroenterologist with expertise in the evaluation and treatment of Crohn’s disease and UC, including the clinical use of TNFα inhibitors like adalimumab. His expertise also includes the design, conduct and evaluation of clinical trials. [ 104 ] Dr.

Howden prepared two reports for this matter, including his initial expert report on the 868 Patent and a responding expert report to Dr. Marshall. [ 105 ] In his first report, he opined the skilled person would be a physician with experience and expertise in the management of patients with IBD. Additionally, given the 868 Patent involved a dosing regimen, Dr. Howden stated the skilled person (or team of persons) would include individuals with experience in deciding the doses to use in clinical trials, such as a clinician and pharmacologist. [ 106 ] For the 868 Patent, Dr.

Howden determined the prior art included extensive information on TNFα inhibitors as of April 9, 2004 (including adalimumab, infliximab and etanercept), the use of TNFα inhibitors to treat IBD, and the doses of adalimumab disclosed to be therapeutically effective. At trial, he stated a skilled person in 2004 would appreciate an association between TNFα inhibitors and Crohn’s disease. In particular, Dr.

Howden referred to Professor van Deventer’s paper, titled " “ Tumour necrosis factor and Crohn’s disease ” " (1997) 40:4 Gut 443-448, which recognized that TNFα was an important pro-inflammatory mediator in Crohn’s disease. [ 107 ] Although the prior art did not specify the dosing regimen claimed by the 868 Patent, Dr. Howden found the loading and induction doses of 160 mg and 80 mg fell within the range of doses of adalimumab previously described as being efficacious for treating IBD.

Additionally, he noted the biweekly (or every other week) maintenance dose of at least 40 mg was the main, regulatory-approved dosing regimen of adalimumab for the treatment of RA. [ 108 ] Dr. Howden opined that a clinician would know that, when treating IBD, a maintenance dosing regimen would be insufficient on its own to treat moderate to severe Crohn’s disease, given an induction phase is crucial to bringing the disease under control.

Therefore, he indicated a clinician would understand that a loading or induction dose should be incorporated with a maintenance dose (and the amount of adalimumab in the loading phase should be larger than the maintenance phase). [ 109 ] Dr. Howden noted a clinician would understand the routine way for selecting a drug’s dosing is to engage in a dose-ranging study. In his report, Dr. Howden stated AbbVie’s internal documents supported his opinion that: (

i) there was a strong expectation that adalimumab would treat Crohn’s disease (and ulcerative colitis); (ii) there was a strong expectation that a dosing regimen for adalimumab for the treatment of Crohn’s disease (and ulcerative colitis) would be selected and tested and demonstrated to be effective; and (iii) the efforts to arrive at the invention of the 868 Patent were routine. [ 110 ] In his responding report, Dr. Howden disagreed with Dr. Marshall on several main points. First, Dr.

Howden did not concur that the results of the 868 Patent in study M02-403 were surprising, as REMICADE had already been regulatory-approved and marketed for the treatment of Crohn’s disease since the late 1990s. Further, REMICADE and adalimumab shared many similarities. Second, Dr. Howden also did not agree that a skilled person would interpret the term " “treating,” " as stated in the 868 Patent for Crohn’s disease and UC, to mean something more than " “simply administering a drug to a patient.” " (

b) Dr. Sharon Baughman [ 111 ] Dr. Baughman is a pharmaceutical scientist with expertise in pre-clinical and clinical pharmacokinetics and pharmacodynamics of protein and small molecule entities. She has extensive experience working at pharmaceutical companies developing novel therapies. She holds a Bachelor of Science in Chemistry from the University of New Orleans and a PhD in Physical Organic Chemistry from Rice University. [ 112 ] Dr. Baughman provided her opinion in relation to the 868 and 917 Patents, specifically focusing on the skilled pharmacologist perspective and the selection of dosing regimens.

She supposedly provided a blind opinion. However, on cross-examination it became apparent that Dr. Baughman had been involved with litigation related to the 868 Patent previously. [ 113 ] During the cross-examination of Dr. Baughman, AbbVie relied on and used Dr. Baughman’s expert report from the Samsung

Bioepis ( " “Bioepis” " ) litigation, sworn on February 9, 2018 [2018 Affidavit], to show she did not provide a blind opinion. [ 114 ] In the previous litigation, Bioepis served a NOA on AbbVie in relation to its proposed adalimumab product, HADLIMA, and the 868 Patent (amongst other patents). In its NOA, Biopeis alleged that HADLIMA would not infringe any of the AbbVie patents, leading AbbVie to apply to this Court pursuant to

section 6 of the Regulations . That matter was subject to a Protective Order, as agreed to by the parties and created by this Court: see AbbVie Corporation v Samsung Biopeis Co, Ltd , 2017 FC 675 at para 4 . The terms of the applicable Protective Order can be found at Appendix A of that decision. The parties settled the matter in 2018; therefore, there was no trial. As a result, the information and documents contained in that matter still remain subject to the Protective Order. [ 115 ] Within the report, Dr. Baughman referred to the dosing regimen of 160 mg, 80 mg and 40 mg every other week for Crohn’s disease.

During cross-examination, Dr. Baughman agreed that it appeared she had been aware of the dosing regimen prior to giving her opinion given the Biopeis litigation. When pressed further, Dr. Baughman stated she did not recall completing this earlier work. (

c) Dr. Daniel Sauder [ 116 ] Dr. Sauder specializes in dermatology. He currently practices at the Dermatology Centre in Toronto, Ontario. He obtained his MD from McMaster University in 1975 and completed his Dermatology Residency at the Cleveland Clinic in Ohio in 1979. Like the other experts in this matter, he has extensive experience in his field and many publications. He also has clinical trial experience, as he has acted as a Principal Investigator or Co-investigator on approximately 50 clinical trials (Phases I to IV). [ 117 ] The Court qualified Dr.

Sauder to give his opinion on the use of biologic medicines, such as TNFα inhibitors, for the treatment of inflammatory skin diseases, including adalimumab for treating HS. His expertise also includes the design and conduct of clinical trials for the treatment of inflammatory skin diseases. [ 118 ] Dr. Sauder provided his opinion on the 917 Patent. He addressed whether the claim terms were described, along with anticipation, inventiveness, and the method of medical treatment. He provided two reports in this matter, including a response to Dr. Solomon’s expert report. (

d) Dr. Robert Falconer [ 119 ] Dr. Falconer is a professor in Bioprocess Engineering in the Department of Chemical Engineering & Advanced Materials at the University of Adelaide in South Australia. Since joining the university in 2019, Dr. Falconer has continued to focus his research on the interactions between proteins, excipients and water for the development of stable protein pharmaceutical formulations. [ 120 ] Dr. Falconer received his BSc degree in Biotechnology from the University of New South Wales in 1984. Dr.

Falconer obtained his PhD in the field of recombinant protein manufacturing process development from the University of Adelaide in 1998. Dr. Falconer has over 30 years of industry and academic research experience in protein chemistry and biotechnology. He has authored and co-authored over 60 papers in scientific journals, with several of his publications involving the stability of proteins and protein pharmaceutical formulations. He has also supervised doctoral students working in the area of protein stability. [ 121 ] Dr.

Falconer was qualified to provide expertise in the field of protein formulation, including formulations for mAbs, as well as protein stability and the techniques used to assess their pharmaceutical formulations. [ 122 ] Dr. Falconer provided two expert reports in this matter for the 458 Patent. [ 123 ] In his initial report, Dr. Falconer stated there was a large amount of knowledge on proteins, including mAbs and pharmaceutical formulations, as of November 2007.

He indicated adalimumab was a well-known anti-tumour necrosis factor alpha ( " “anti-TNFα” " ) antibody, and an aqueous pharmaceutical formulation of adalimumab had been extensively studied and approved for medical use in the treatment of RA in 2002 in the US. [ 124 ] At trial, Dr. Falconer stated a skilled person working on a formulation would have a science background.

In his report, he indicated this person would have a sound knowledge of mAb chemistry and stability and a PhD in biology, chemistry, biochemistry or chemical engineering, with at least two years of practical experience in developing mAb pharmaceutical formulations for therapeutic use. Alternatively, Dr. Falconer suggested this person could have lesser qualifications, such as a master's or bachelor's degree, with more practical hands-on formulation experience. [ 125 ] Dr.

Falconer noted the overarching inventive concept of the 458 claims is an aqueous pharmaceutical formulation comprising an antibody or fragment of an antibody (including adalimumab) at a concentration of at least 50 mg/mL with essentially no buffering system and little or no ionic excipients. [ 126 ] Dr. Falconer opined the 181 Application disclosed and enabled each of the essential elements of the 458 claims. Further, in discussing pain associated with injection, Dr. Falconer noted there was an increasing interest during this time to reduce pain on injection. [ 127 ] During questioning, Dr.

Falconer testified that there were no significant differences between the 458 Patent and the 181 Application and that, if there were substantial differences, somebody familiar with the literature and skilled in the art would have been able to bridge those gaps. Dr. Falconer opined a skilled person would understand that a high concentration of adalimumab formulation would provide the buffering capacity that is required to maintain the preferred pH. As well, a skilled person would learn that having a low ionic content was advantageous. [ 128 ] Dr. Falconer opined it was self-evident to try the invention.

Additionally, he stated a skilled person would have been motivated to increase the adalimumab concentration, as a lower volume meant less pain. [ 129 ] Dr. Falconer referred to literature which described significant gains in protein stability when increasing the protein concentration.

[ 130 ] Dr. Falconer also stated it was more or less self-evident that what was being tried should work. Based on the literature, he indicated there was a high probability that a stable high concentration adalimumab formulation could be made. He also indicated there were a finite number of identified predictable solutions. (

e) Dr. Laurence Rubin [ 131 ] Dr. Rubin is a doctor with a specialization in rheumatology. He is presently a staff physician in the Rheumatology Division and the Metabolic Bone Clinic at Saint Michael’s Hospital in Toronto. He obtained his MD from the University of Ottawa and has significant expertise in rheumatology. [ 132 ] Dr. Rubin was qualified as a medical doctor, clinical rheumatologist, researcher and professor of medicine, with expertise in rheumatology, including the past and present treatment of chronic inflammatory rheumatic diseases in Canada using biologic medicines and biosimilars.

He also responded to Dr. Mysler’s Report. [ 133 ] His evidence pertained to biosimilars in Canada and injection site pain. His evidence was that, if SIMLANDI and Yuflyma were not available in Canada, then some patients forced to switch to another adalimumab formulation might have increased injection pain or poor tolerance, resulting in less adherence to the treatment. (

f) Dr. Rosemary A. Bacovsky [ 134 ] Dr. Bacovsky is an experienced pharmacist, including prior work experience in government policy positions. She has acted as a consultant in many roles, including for private companies, the government, and various health authorities. [ 135 ] With respect to SIMLANDI’s place in the Canadian marketplace, the Court took Dr. Bacovksy’s evidence as read. (

g) Ms. Ashley Beacom [ 136 ] Ms. Beacom provided a report regarding the translation of some of the laboratory materials. She attested to the accuracy of the translation from German to English. III. Issues [ 137 ] The Parties filed the following Joint Statement of Issues: A. The 868 Patent 1 . Are claims 1-5 contrary to

section 28.3 of the Patent Act (i.e. obvious)? 2 . Are claims 1-5 contrary to

section 2 of the Patent Act (i.e. patentable subject matter) for claiming a method of medical treatment? B. The 917 Patent 1 . Are claims 1 and 3-5 contrary to

section 28.2 of the Patent Act (i.e. anticipated) in view of the 868 Application? 2 . Are claims 1 and 3-5 contrary to

section 28.3 of the Patent Act (i.e. obvious)? 3 . Are claims 1 and 3-5 contrary to

section 2 of the Patent Act (i.e. patentable subject matter) for claiming a method of medical treatment? 4 . Are claims 1 and 3-5 contrary to subsection 38.2(2) of the Patent Act for containing a claim term that cannot reasonably be inferred from the 917 Patent’s specification or drawings contained in the application on its filing date and/or for claiming subject matter that was neither made nor disclosed by the named inventors? C. The 458 Patent 1 . Are the 458 claims contrary to

section 28.2 of the Patent Act (i.e. anticipated) in view of WO 2006/138181? 2 . Are the 458 claims contrary to

section 28.3 of the Patent Act (i.e. obvious)? 3 . Are the 458 claims invalid for overbreadth? 4 . Are the 458 claims invalid for same-invention and/or obviousness-type double patenting in view of CA 2,815,689? D. Infringement 1 . Does JAMP infringe the asserted claims, as alleged by AbbVie? E. Entitlement to Relief

1 . Is AbbVie entitled to a permanent injunction (if infringement is found) and, if it is entitled to a permanent injunction, what ought to be the proper scope of said injunction? 2 . Is JAMP required to deliver up or destroy its infringing products (if infringement is found)? [ 138 ] Prior to the commencement of the trial, a disagreement arose as to whether JAMP was able to argue previously pleaded invalidity allegations for which it had provided no expert evidence.

AbbVie took the position that AbbVie bears the burden on invalidity and that, having delivered no expert evidence on some invalidity allegations, JAMP was not entitled to advance them at trial. [ 139 ] On November 7, 2022, I directed that JAMP was not precluded from advancing the pled invalidity issues. [ 140 ] JAMP preserved the right to advance lack of utility (i.e. not demonstrated and/or not soundly predicted) in respect of the 868 Patent. Ultimately, JAMP did not advance this invalidity ground in its written closing submissions nor in its oral closing arguments.

As JAMP bears the burden of establishing this invalidity ground, it has not proven it and this issue is dismissed without further reasons. [ 141 ] On December 6, 2022, the parties provided an updated Joint Statement of Issues. In that update, JAMP stipulated to infringement of the 458 Patent claims, subject only to their validity. Accordingly, to the extent that any of the 458 Patent claims are valid, then JAMP agrees that its SIMLANDI products infringed the Asserted claims. IV. Applicable Legal Framework [ 142 ] AbbVie has the burden of proving infringement on a balance of probabilities.

Where validity is at issue, the starting point is that the patent is presumed to be valid: subsection 43(2) of the Patent Act . [Appendix A]The burden is on JAMP to prove each ground of invalidity on a balance of probabilities: Teva Canada Innovation v Pharmascience Inc , 2020 FC 1158 at para 156 [ Pharmascience ]. A. General Principles of Claim Construction [ 143 ] The principles of claim construction are well-established.

The Federal Court of Appeal summarized these principles at paragraphs 30-34 of Tearlab Corporation v I-Med Pharma Inc , 2019 FCA 179 . [ 144 ] At paragraphs 33 to 35 of Corlac Inc v Weatherford Canada Inc , 2011 FCA 228 [ Weatherford ], the Federal Court of Appeal explained that, where the validity of a dependent claim depends on the inventiveness of the independent claim, the first instance court is not required to construct elements of the dependent claim which were not in dispute.

The Federal Court of Appeal upheld this principle in Swist v MEG Energy Corp , 2022 FCA 118 , again re-stating that, " “where the first instance court correctly determines the validity of the dependent claims rests on the inventiveness of the independent claim, it is not required to construe elements of the dependent claims that were not actually in dispute” " (at para 22). B.

Prior Art [ 145 ] Prior art is " “the collection of learning in the field of the patent at issue” " and " “comprises any publicly available teaching, however obscure or not generally accepted” " : Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC , 2016 FCA 119 at para 23 [ Mylan Pharmaceuticals ULC ]. [ 146 ] For patent cases, prior art can be used " “to found an allegation that prior art anticipated the invention or rendered it obvious” " : Mylan Pharmaceuticals ULC at para 25 . [ 147 ] Common general knowledge is a subset of the state of the art: Hospira Healthcare Corporation v Kennedy Trust for Rheumatology Research , 2020 FCA 30 at para 84 [ Hospira ]. [ 148 ] The state of the art is no longer limited by what the skilled person could locate in a reasonably diligent search.

At paragraphs 83 to 86 of Hospira , the Federal Court of Appeal held that it is an error to exclude from consideration prior art that was available to the public at the relevant date because it would not have been located through a reasonably diligent search. [ 149 ] In Gemak Trust v Jempak Corporation , 2022 FCA 141 [ Gemak ], the Federal Court of Appeal held: [100] Thus, it is no longer required that prior art be available to the POSITA through a reasonably diligent search for it to be potentially relevant for the purpose of the obviousness or anticipation analyses.

That said, knowledge that is only discoverable through a reasonably diligent search is not, and has never been, considered to be part of the common general knowledge. [Emphasis added.] C.

Common General Knowledge [ 150 ] Common general knowledge is the knowledge that was generally known at the relevant time by the person skilled in the art or science to which the patent relates: Janssen Inc v Pharmascience Inc , 2022 FC 1218 at para 114 [ Janssen 2022], citing Apotex Inc v Sanofi-Synthelabo Canada Inc , 2008 SCC 61 at para 37 [ Sanofi or Plavix 1]; Bell Helicopter Textron Canada Limitée v Eurocopter, société par actions simplifiée, 2013 FCA 219 at paras 63-65 [ Eurocopter] .

Common general knowledge informs the way claims and specifications are read by the POSITA: Gemak at para 98 ; Mylan Pharmaceuticals at para 25.

[ 151 ] The relevant date for the purposes of construction is the date of publication, while the relevant date for the purposes of invalidity is the claim date, which is the priority date if there is one, or the filing date if there is not: Guest Tek Interactive Entertainment Ltd v Nomadix, Inc , 2021 FC 276 at para 51 . [ 152 ] The Federal Court of Appeal recently underscored that common general knowledge does not include all of the information in the public domain: Gemak at para 95 . Not all information available to the skilled person is necessarily common general knowledge.

A piece of particular knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of the common stock of knowledge relating to the art: Gemak at paras 95-96 . D. Anticipation [ 153 ] Anticipation law is central to this dispute. The parties agree in broad strokes on the legal principles of anticipation.

However, the parties disagree as to whether prior art which leaves open choices for the skilled person, or which broadly encompasses the claimed invention, is sufficient to invalidate the patents based on anticipation. [ 154 ] The relevant statutory provisions are found in

section 28.2 of the Patent Act . [Appendix A] [ 155 ] Both parties rely on Sanofi , albeit through a different lens and understanding. JAMP heralds Sanofi to represent a " “sea change” " in anticipation law. AbbVie, instead, relies on Sanofi as a clarification and refining of the test from Beloit Canada Ltd v Valmet OY (1986), 8 CPR (3d) 289 (FCA) [ Beloit ] , saying that Sanofi does not represent a significant change in the law. [ 156 ] It is not in dispute that the law of " “anticipation requires proof of both disclosure and enablement” " ( Sanofi at para 42).

Lord Hoffman also explained in Synthon BV v SmithKline Beecham plc , [2006] 1 All ER 685 , [2005] UKHL 59 [ Synthon ] that these two requirements must be kept distinctly separate (at para 30). Sanofi and Synthon clearly direct that experimentation or trial and error is permitted at the enablement stage, not the disclosure stage. [ 157 ] I understand that the parties disagree as to whether prior art that discloses a range can anticipate a point within a range or embodiment.

For example, has disclosure occurred if the range is 0.2-400 mg in the prior art, and the subsequent patent claims about 10 mg or a narrower range such as 0.10-100 mg. [ 158 ] JAMP relies on several recent cases where the Federal Court held a range or a broad disclosure can anticipate a point within a range or an embodiment: Hoffman-La Roche Limited v Apotex Inc , 2013 FC 718 [ Hoffman-La Roche ] ; Alcon Canada Inc v Apotex Inc , 2014 FC 699 [ Alcon Canada ] ; Eli Lilly Canada Inc v Mylan Pharmaceuticals ULC , 2020 FC 816 [ Eli Lilly 2020] ; Swist v MEG Energy Corp , 2021 FC 10 . [ 159 ] In contrast, AbbVie argues that, where the disclosure broadly includes or encompasses the claimed invention, without necessarily planting the flag at the precise destination, then this will be insufficient to meet the requirements of anticipation.

AbbVie points to the Federal Court of Appeal’s decision in Apotex Inc v Shire LLC , 2021 FCA 52 [ Shire ] at paragraph 45 , and says that the cases relied on by JAMP must be read in light of this decision. [ 160 ] To add to this discussion, Professor Norman Siebrasse’s [Siebrasse] commentaries have strongly stated that the Federal Court had it wrong in both Alcon Canada and in Hoffman-LaRoche : Norman Siebrasse, " “Construction of the Inventive Concept is Determinative of Obviousness” " (27 August 2014), Sufficient Description (blog), online: <http://www.sufficientdescription.com/2014/08/>; Norman Siebrasse, " “Time to Abandon the Doctrine of Selection Patents?” " (26 July 2013), Sufficient Description (blog), online: <http://www.sufficientdescription.com/2013/07/time-to-abandon-doctrine-of-selection.html>. [ 161 ] Professor Siebrasse also states that the Federal Court was " “clearly wrong” " in Eli Lilly 2020 : Norman Siebrasse, " “Does a Range Anticipate a Point Within the Range?” " (23 September 2020), Sufficient Description (blog), online: <http://www.sufficientdescription.com/2020/09/does-range-anticipate-point-within-range.html>. [ 162 ] In those cases, the trial judge found that a range anticipated a point within the range.

Siebrasse said that, while it might be obvious to determine the optimum dosage by routine experiments, this does not mean the dosage is anticipated by the disclosure of a range. In Eli Lilly 2020 , Siebrasse determined the Federal Court conflated the disclosure and enablement steps by finding a range plants the flag.

In his opinion, the two requirements must be kept distinct; it is not enough to say, given the prior art, that a POSITA would be able to come to the invention, since trial and error is permitted only at the enablement stage. [ 163 ] Siebrasse’s final criticism of the Federal Court is Merck & Co, Inc v Pharmascience Inc , 2010 FC 510 , which is a decision that some of these other cases have relied on: Norman Siebrasse, " “Teaching Away Irrelevant to Anticipation” " (23 May 2019), Sufficient Description (blog), online: <http://www.sufficientdescription.com/2019/05/teaching-away-irrelevant-to-anticipation.html>.

In that decision, Siebrasse says his position is based on the rule that, " “ " " A signpost, however clear, upon the road to the patentee’s invention will not suffice.

" " The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee” " ( General Tire & Rubber Co v Firestone Tyre & Rubber Co , [1972] RPC 457 at 486; Sanofi at para 21). [ 164 ] In Apotex Inc v Shire LLC , 2018 FC 637 [ Shire 2018 ] , Justice Fothergill recognized Siebrasse’s criticism of Hoffman-La Roche : Norman Siebrasse, " “Time to Abandon the Doctrine of Selection Patents?” " (26 July 2013), Sufficient Description (blog), online: <http://www.sufficientdescription.com/2013/07/time-to-abandon-doctrine-of-selection.html>.

Justice Fothergill acknowledged Siebrasse’s conclusion that Hoffman-La Roche was very similar factually to Sanofi and the two decisions could not be reconciled ( Shire 2018 at para 95 ). [ 165 ] Wrapped around this discussion is whether it matters if the patent is a selection patent. That issue was settled in Shire , as the FCA said the validity analysis does not change depending on whether the patent is a selection patent or not. The FCA noted a selection patent is not even contained in the Patent Act : Shire at paras 31-34 .

[ 166 ] I find that, as is often the case, the application of the law depends on the facts. In this case, the issue is whether the prior art, that disclosed a range, planted the flag at a precise enough point to move to the second stage, which is whether it was enabled after some experimentation. [ 167 ] Support for this somewhat middle ground is based on Justice Rennie’s writing in Shire . In the decision, Justice Rennie stated that ranges do not necessarily anticipate points. But they may .

He noted, " “A genus may, depending on its size, the language of the claims, context and included examples, anticipate the individual species” " : Shire at para 46 . [ 168 ] In my opinion, if the range is sufficiently small, based on the factual situation (e.g. in a pharmaceutical context 0.10-0.12 mg/ml), it can be said that inventor planted their flag with sufficient specificity to anticipate a point in a claim. [ 169 ] To unpack this a bit further, we can look at what lead Justice Rennie to this finding.

As well, we can examine what examples are seen as having too broad a range, and what might fall into the anticipatory range. [ 170 ] Justice Rennie at paragraphs 45-46 of Shire said: [45] It would also be inconsistent with the principle articulated, and noted earlier, in General Tire , that “[t]he prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee” (at page 486). The point was also made succinctly in Ranbaxy Laboratories Limited v.

AstraZeneca AB , [2013] FCA 368 (Aus.) at paragraph 170: .… it is not sufficient for a prior publication to merely “include” or “encompass” the claimed invention—a broad disclosure will not necessarily anticipate a later, more specific claim: see eg Eli Lilly [2013] FCA 214 at [272] to [293] and the authorities cited therein. [46] This is not to say that anticipation has no role in the context of genus disclosures—to the contrary, it is very much alive.

A genus may, depending on its size, the language of the claims, context and included examples, anticipate the individual species (see, e.g., Aux Sable Liquid Products LP v. JL Energy Transportation Inc. , 2019 FC 581 , [2020] 1 F.C.R. 547 at paragraphs 90 and 98 ; Valence T echnology Inc. v. Phostech Lithium Inc ., 2011 FC 174 , 92 C.P.R. (4th) 123 , at paragraphs 228-230 , affd 2011 FCA 237 , 96 C.P.R. (4th) 207 ). [47] Therefore, the ultimate answer to the question of whether the inventor “planted a flag” at the compound is driven by the specific evidence in each case.

Here, the Judge identified differences that relate to the specific asserted claims within CA ′646. In doing so, he found that those specific claims were not anticipated. The Judge undertook the exercise required of him by Sanofi .

The Judge identified the correct test for anticipation (Decision, at paragraphs 99–100) and his conclusion that CA ′646 was not anticipated by AU ′168 was amply supported by the evidence. [Emphasis added.] [ 171 ] Looking at what Justice Southcott in Aux Sable held: [90] …Aux Sable also submits, and I agree, that Federal Court jurisprudence demonstrates that the prior disclosure of a point within a range prescribed by a patent is anticipatory (see, e.g. Baker Petrolite Corp. v. Canwell Enviro-Industries Ltd. , 2002 FCA 158 , [2003] 1 F.C. 49 ( Baker Petrolite ), at paragraph ; Calgon Carbon Corporation v.

North Bay (City) , 2006 FC 1373 , 56 C.P.R. (4th) 281 ( Calgon Carbon ), at paragraphs , 153 and 163). [ 172 ] Justice Rothstein, who authored the Sanofi decision in 2008, wrote in 2002 for the FCA in Baker Petrolite (at para 42 ) that, " “ The Board therefore does not accept the patent proprietor's submission to the effect that a complete analysis of a prior used product must be possible, so as to enable an exact reproduction of such product , in order to destroy the novelty of the claimed product” " [Emphasis in bold in original; other emphasis added]. [ 173 ] I find that the law has developed that, where the evidence presented at trial shows that the range is narrow enough, such that a flag can be planted based on the context and examples given, then it is anticipated.

If the evidence shows a very broad range that the Judge, with the experts’ assistance (if needed), does not see it as a precise enough to plant the flag before proceeding to the enablement stage, then it fails at the disclosure stage. E. Obviousness [ 174 ] The starting point for an analysis of obviousness is

section 28.3 of the Patent Act . [Appendix A] [ 175 ] Obviousness is assessed against the four-part test established in Sanofi : 1. (

a) Identify the notional “person skilled in the art”; (

b) Identify the relevant common general knowledge of that person; 2. Identify the inventive concept of the claim or if that cannot readily be done, construe it; 3. Identify what, if any, differences exist between the matter cited as forming part of the “state of the art” and the inventive concept of the claim or the claim as construed; and 4. Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention? [ 176 ] The threshold for inventiveness is low – a " “mere scintilla of invention” " will suffice to support the validity of a patent: Valeant

Canada LP/Valeant Canada SEC v Generic Partners Canada Inc , 2019 FC 253 at para 105 [ Valeant Canada ], citing Diversified Products Corp v Tye-Sil Corp (1991), 35 CPR (3d) 350 (FCA) at 365 . [ 177 ] As AbbVie emphasized, the Court must be cautious not to employ hindsight bias in its obviousness analysis: Valeant Canada at para 104 ; Meda AB v Canada (Health) , 2016 FC 1362 at para 138 ; Bridgeview Manufacturing Inc v 931409 Alberta Ltd (Central Alberta Hay Centre) , 2010 FCA 188 at para 50 . [ 178 ] When assessing obviousness, the trier of fact can look to the cumulative effect of the prior art that can be considered by a skilled person: Donald Cameron, Canadian Patent Law Benchbook , 4th ed (Toronto: Thomson Reuters, 2022) at 241.

In addition, the Court should undertake the inquiry on a claim-by-claim basis: Zero Spill Systems (Int’

l) Inc v Heide , 2015 FCA 115 at para 85 [ Zero Spill Systems ].

(1) Obvious to Try [ 179 ] In Pharmascience Inc v Teva Canada Innovation , 2022 FCA 2 [ Pharmascience 2022] , the Court clarified that the fourth step in the Sanofi obviousness test is the " “obvious to try” " test. Under the fourth part of the Windsurfing/Pozzoli test, in some cases a secondary analysis will be required to determine whether the " “obvious to try” " test applies. In Sanofi , the Supreme Court of Canada outlined where the obvious to try test will arise.

The Court explained at paragraph 68: In areas of endeavour where advances are often won by experimentation, an “obvious to try” test might be appropriate. In such areas, there may be numerous interrelated variables with which to experiment.

For example, some inventions in the pharmaceutical industry might warrant an “obvious to try” test since there may be many chemically similar structures that can elicit different biological responses and offer the potential for significant therapeutic advances. [ 180 ] This Court and the Federal Court of Appeal have frequently held that the " “obvious to try test” " applies in pharmaceutical matters that require experimentation: Janssen Inc v Teva Canada Ltd, 2020 FC 593 at para 198 [ Janssen 2020]; Teva Canada Limited v Novartis Pharmaceuticals Canada Inc , 2013 FCA 244 at para 7 . [ 181 ] At paragraph 43 of Bristol-Myers Squibb Canada Co v Teva Canada Limited , 2017 FCA 76 [ Bristol-Myers Squibb ], the Federal Court of Appeal outlined the non-exhaustive list of relevant factors to consider (citing Sanofi at paragraph 69): 1.

Is it more or less self-evident that what is being tried ought to work? Are there a finite number of identified predictable solutions known to persons skilled in the art? 2. What is the extent, nature and amount of effort required to achieve the invention? Are routine t

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