Hoffman-La Roche Limited v. Apotex Inc., 2013 FC 718 (2013)

Parts:Hoffman-La Roche Limited v. Apotex Inc.
Reporting Judge:The Honourable Madam Justice Kane
Docket Number:T-1247-11
 
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Federal Court - Hoffman-La Roche Limited v. Apotex Inc.

Source: http://decisions.fct-cf.gc.ca/en/2013/2013fc718/2013fc718.html

Date: 20130712

Docket: T-1247-11

Citation: 2013 FC 718

Ottawa , Ontario , July 12, 2013

PRESENT: The Honourable Madam Justice Kane

BETWEEN:

HOFFMAN-LA ROCHE LIMITED

Applicant

and

APOTEX INC.

and

THE MINISTER OF HEALTH

Respondents

and

F. HOFFMAN-LA ROCHE AG

Respondent Patentee

PUBLIC REASONS FOR JUDGMENT AND JUDGMENT

(Confidential Reasons for Judgment and Judgment Issued June 27, 2013)

INDEX PARA

INTRODUCTION.............................................................................................................. 4

THE PARTIES.................................................................................................................. 12

THE ‘721 PATENT GENERALLY................................................................................. 19

THE EVIDENCE.............................................................................................................. 26

ISSUES............................................................................................................................. 28

THE NOTICE OF ALLEGATION.................................................................................. 44

BURDEN.......................................................................................................................... 57

PERSON SKILLED IN THE ART.................................................................................. 65

THE ‘721 PATENT IN DETAIL...................................................................................... 71

CONSTRUCTION OF THE CLAIMS............................................................................ 90

THE INVENTION ........................................................................................................... 99

IS IT A SELECTION PATENT?................................................................................... 133

ANTICIPATION............................................................................................................ 179

OBVIOUSNESS............................................................................................................. 243

CLAIMS BROADER THAN THE INVENTION MADE OR DISCLOSED............. 355

INFRINGEMENT.......................................................................................................... 365

CONCLUSIONS AND COSTS..................................................................................... 400

[1] This is an application brought under the provisions of the Patented Medicines (Notice of Compliance) Regulations SOR/93-133, as amended [ NOC Regulations ] to prohibit the Minister of Health from issuing a Notice of Compliance to Apotex in respect of its valganciclovir hydrochloride 450mg tablets (the Apotex product) until the expiry of Canadian Letters Patent No 2154721 (the '721 Patent) on July 26, 2015.

[2] For the reasons that follow, I find that the allegations with respect to invalidity are justified and the allegation with respect to non-infringement of claim 4 is justified.

[3] The application is dismissed with costs to Apotex.

INTRODUCTION

[4] In the 1990s, ganciclovir was recognized as the leading drug for the treatment of certain herpes viruses, particularly cytomegalovirus [CMV], a type of herpes virus. The parties and the experts described ganciclovir as an antiviral nucleoside, which is a compound that disrupts DNA synthesis in, for example, virally-infected cells. Disrupting viral replication induces the death of the infected cell. A nucleoside is a compound formed by joining a base moiety with a sugar moiety. A disadvantage of ganciclovir was its limited oral bioavailability. Although it could be more effective when administered intravenously [IV], this mode had other disadvantages including inconvenience for patients and potential infections, particularly in immunocompromised patients. An improvement in the bioavailability of ganciclovir for oral administration was, therefore, desired.

[5] Acyclovir and penciclovir were other antiviral nucleosides that were also effective against various strains of the herpes virus. However, they also shared the disadvantage, when orally administered, of poor absorption across the gut (small intestine) into the blood stream. These drugs were, therefore, also generally administered by IV (directly into the bloodstream). Several research groups were seeking to improve the oral bioavailability of these compounds in the 1980s and 90s. As explained by the experts, one of the several possible approaches for improving the bioavailability of a drug like ganciclovir was to link the molecule to another compound, referred to as a pro-moiety, (often an amino acid) and to thereby create a prodrug. A prodrug is a compound that has improved absorption and is metabolized to the active drug after absorption (valganciclovir is a prodrug formed by the molecular combination of ganciclovir with the amino acid, mono-L-valine).

[6] The intended mechanism of action of a prodrug is that the pro-moiety will help deliver the active medicine more effectively to the site of action. Prodrugs are designed such that the pro-moiety (in this case, the amino acid ester) is hydrolyzed, or cleaved, from the active drug compound at an appropriate point after absorption into the body.

[7] Doctor McGuigan, an expert for Apotex, noted at paragraph 54 of his affidavit that by 1994 it was well known that prodrugs are often used where a drug has suboptimal bioavailability. He described a prodrug as a molecular derivative of the parent drug which requires structural transformation to the active drug in vivo (in the body). Once activated in the body it can then exert its pharmacological action. A prodrug often results in improved tissue penetration by altering the lipophilicity and/or the water solubility of the drug. Prodrugs can also take advantage of the various active transport mechanisms available in the body, in particular when the prodrug resembles natural metabolites, such as with amino acid esters. The prodrug form is better absorbed, and after biotransformation, results in a greater exposure to the active drug that would have occurred had the parent drug form been administered.

[8] He also noted that the majority of produgs are esters (para 55). An ester is a compound produced through the reaction of an acid (with a -COOH functional group) with a compound having a hydroxyl group (-OH).

[9] Dr McGuigan indicated that in order to be suitable, a nucleoside prodrug would need improved bioavailability (assuming that the desired improvement is higher oral bioavailability) and would have to be: soluble enough to be dissolved in the stomach; stable enough to survive the acidic environment of the stomach; have the ability to pass through the gut; reach the blood stream; and, release the active agent. Additionally, a suitable prodrug would have to be acceptable for use as a pharmaceutical.

[10] Roche holds the patent for valganciclovir, which is more fully described below, and which the inventors claim meets these desired characteristics.

[11] In GlaxoSmithKline Inc v Pharmascience Inc , 2011 FC 239, [2011] FCJ 287, Justice Hughes explained the nomenclature of NOC proceedings and the requirements of the Notice of Allegation [NOA] as follows:

[38] The NOC Regulations identify two groups of persons, a “first person”, commonly called the “brand”, who is the person owning or licensed under a patent and who has received permission to sell a drug somehow relating to that patent in Canada (section 4(1)). A “second person”, commonly called a “generic” is a drug company wanting to take advantage of much of the material submitted by the first person in order to obtain approval itself to sell the drug. The second person must notify the first person providing particulars of its application to secure approval and to state that the patent will not be infringed or is invalid or that the second person will wait for the patent to expire. That notification takes the form of a “Notice of Allegation” (NOA).

[39] That Notice of Allegation (NOA) is required by subsection 5(3)(b)(ii) of the NOC Regulations to include “a detailed statement of the legal and factual basis for the allegations”… .

THE PARTIES

[12] The applicant, Roche, is a “first person” as described in the NOC Regulations . It has listed the '721 Patent in accordance with those Regulations . Roche has obtained a Notice of Compliance [NOC] to sell valganciclovir hydrochloride, which it does under the brand name Valcyte, from the Minister of Health.

[13] The applicant, Roche, claims to be the owner of the '721 Patent and this is not contested in these proceedings.

[14] The respondent, Apotex, is a “second person” as described in the NOC Regulations . It seeks to sell a generic version of Roche’s valganciclovir drug. To do so, it must receive a NOC from the Minister of Health. In accordance with the NOC Regulations , Apotex served Roche with a Notice of Allegation [NOA] dated June 14, 2011.

[15] In the NOA, Apotex alleges that claims 4-8 and 10 of the ‘721 Patent would not be infringed, and that the patent is invalid on the grounds of anticipation, obviousness, and overbreadth or claims broader than the invention made or disclosed. Apotex also alleges that it does not infringe any valid claim in making, constructing, using or selling its Apotex product.

[16] The respondent, the Minister of Health, who has various responsibilities under the NOC Regulations , including the issuance of an NOC to a “second person” such as Apotex, took no active role in these proceedings.

[17] The respondent, Apotex, submits that the applicant, Roche, has not honored its part of the bargain upon which the ‘721 Patent is based. The nature of this bargain was described in Apotex Inc v H Lundbeck...

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