Astrazeneca Canada Inc. v. Ranbaxy Pharmaceuticals Canada Inc.: Not So "Obvious to Try"

Earlier this week, the Federal Court granted Astrazeneca’s order prohibiting the Minister of Health from issuing a notice of compliance to Ranbaxy in relation to tableted dosage forms of the proton pump inhibitor, omeprazole until the expiry of Canadian Patent No. 2,170,647.

A copy of the decision can be found at the following link: http://decisions.fct-cf.gc.ca/en/2013/2013fc232/2013fc232.html

Omeprazole is used to treat gastroesophageal reflux disease (GERD) and other gastric ailments.

The only issue at question was whether Ranbaxy’s invalidity allegations were justified (see paragraph [2] of the FC decision) and in particular, was the subject matter of the claims of the ‘647 patent obvious in view of the prior art.

The question of obviousness was assessed using the four question analysis set out by the Supreme Court of Canada in Apotex Inc. v Sanofi-Synthelabo Canada Inc., 2008 SCC 61 at paragraph 67, [2008] 3 SCR 265:

(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 in question 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;  

(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? (paragraph [11] of FC decision) 

The Parties were generally in agreement with respect to the answer to the first three questions with the inventive concept being the “formulation of a tablet of enteric coated pellets of omeprazole, whose pellets can retain their acid resistance after tablet compression”. (see paragraph [61] of the FC decision).

The main point of contention between the Parties was with respect to the fourth question. Astrazeneca argued “that the prior art would have directed the skilled person away from concluding that an acid sensitive drug, such as omeprazole, could have been formulated into a multiple unit tableted enteric dosage form.” (paragraph [16] of the FC decision). In contrast, Ranbaxy argued that the “person skilled in the art would view the making of a tablet formulation of enteric coated omeprazole pellets to be something that could be accomplished directly and without difficulty using routine formulation and optimization techniques known at the time”. (paragraph [33] of the FC decision).

The “obvious to try” test was considered appropriate in this case for assessing the fourth question. The Federal Court addressed the “obvious to try” test using the following questions as originally put forward in Sanofi-Synthelabo:

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 trials carried out or is the experimentation prolonged and arduous, such that the trials would not be considered routine?  

3. Is there a motive provided in the prior art to find the solution the patent addresses? (paragraph [65] of FC decision) 

Several key facts were considered relevant to answering these questions, namely: ·

• The experts “agree[d] that there are numerous variables which must be accounted for including: the amount of plasticizer, the composition of plasticizer, what coating agent should be used, what quantity of coating agent should be used, the size of the sub-unit, what external additives, the rate and magnitude of pressure applied during tabletting, the quantity and composition of cushioning material, and whether all of this complies with pharmacopeial standards.” (paragraph [68] of FC decision) · 

• There was a 2011 paper that indicated “that as a result of the numerous considerations “…production of such a dosage form [is] technologically an extremely complex process.”” (see paragraph [72] of the FC decision) · 

• Only five drugs that had gone to market in enteric coated pellet format. (see paragraphs [21] and [72] of FC decision) 

In view of the above, the Federal Court concluded that “the need for a solution is evident from the prior art; namely, an enteric coating suitable for dispersed omeprazole delivery, however, that solution is not provided for in the prior art. The prior art teaches away from the existence of such a solution or alternately indicates that such a solution is extremely complex and technically difficult to produce. Therefore, the enteric coating is not self-evident and so it is necessary to move on to the second stage of the “obvious to try” test.” (paragraph [70] of FC decision). The Federal Court further concluded that “facts point to a significant amount of effort required to obtain the desired result.” (paragraph [73] of the FC decision). The Federal Court appears to have found the 2011 article particularly persuasive noting in the decision that “[p]resumably manufacturing and drug delivery technology have advanced between 1994 [the priority date of the patent] and 2011. It is therefore reasonable to presume that in 1994, development of such dosage forms remained at least an extremely complex process.” From the decision, the expert for Ranbaxy appears to have dismissed this paper “due to its origin in Slovenia” (paragraph [20]).

As a Patent Agent I found the reliance on the 2011 paper particular interesting as it supports the use of post filing art to counter obviousness objections, however, such a strategy must be used cautiously to avoid calling into question enablement of the claimed invention. With respect to whether there was motivation in the prior art, the Federal Court noted that “[i]n the context of the “obvious to try” test, motivation disclosed in the prior patent would be indicative of a marketplace that would actively seek the (subsequently) patented solution. If other parties were motivated to find the solution and yet were unable or unwilling to do so prior to the patent being obtained, this factor would point to a solution that was not “obvious to try”.” (paragraph [82] of the FC decision)

By Claire Palmer

When is An Extended Release Tablet "Obvious to Try"?

The Federal Court released a decision to dismiss an application under the provisions of the Patented Medicines (Notice of Compliance) Regulations (the PM(NOC) Regulations) to prohibit the issuance of a Notice of Compliance to Teva Canada Limited (Teva) in respect of AstraZeneca’s quetiapine fumarate extended release tablets (sold under the brand name SEROQUEL XR) until the expiry of Canadian Patent No. 2,251,944 (“’944 Patent).

SEROQUEL XR is a sustained release formulation of a drug effective in treating various psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder.

The key issue addressed in this decision is the invalidity of the ‘944 Patent on the basis of obviousness. Ambiguity was a second basis of invalidity. It however was not explored in the decision. The Court, however, stated that ambiguity is truly a last resort, rarely, if ever, to be used.

Obviousness 

Prior to an assessment of validity the claims must be construed purposively. The construction of the claims was not at issue in this case (see paragraph [12]). With the parties agreeing that the patent at issue claims a sustained release formulation of quetiapine hemifumarate, made up of: (i) the particular gelling agent hydroxypropyl methylcellulose [HPMC]; (ii) the hemifumarate salt of quetiapine; and (iii) one or more pharmaceutically acceptable excipients (see paragraph [12]).

A second component of the claim construction was an assessment of the inventive concept of the claims. The Court noted that “[w]here, as in this case, the inventive concept of the claims is not discernible from the claims themselves because they present a bare chemical formula, the Court is directed to read the specification in the patent to determine the inventive concept of the claims”. The Court further stated that as established previously, “the entire specification, including the claims, must be considered in determining the nature of the invention”.

The Court however cautioned in paragraph [13] that:

this does not give the Court free rein to construe the claims as broadly or as narrowly as it wishes. The patentee is “entitled to have the question of obviousness determined by refer. 

The Court held that the key elements of the inventive concept claimed by the ‘944 Patent are: (1) a decreased occurrence of dose dumping; and (2) a less frequent dosing regimen.

Applying the four-step guide for assessing obviousness as established by the Supreme Court of Canada in Apotex Inc. v. Sanofi-Synthelabo Canada Inc [Sanofi], it was agreed that the “obvious to try” test was appropriate for the present case. It was stated in the Sanofi case that:

For a finding that an invention was “obvious to try”, there must be evidence to convince a judge on a balance of probabilities that it was more or less self-evident to try to obtain the invention. Mere possibility that something might turn up is not enough. [emphasis added]. 

There was a disagreement between the parties about the parameters of the “obvious to try” test.

AstraZeneca focused on the results of experimentation and took the position that “it must be obvious that successful results will be achieved before any experimentation was carried out”. Teva’s position was that a patent claim “will be obvious if it was more or less self-evident to try to obtain the invention”. The Court accepted Teva’s interpretation of the parameters of the test.

The Court adopted the standard laid out in Pfizer Canada v. Apotex FC 8(2009), which states that the “predictable”, and therefore obvious, solutions are equivalent to ‘solutions that provide ‘a fair expectation of success’”. The Court held that “it was self-evident or plain that there was a fair expectation that a sustained release formulation of quetiapine using HPMC would be successful”.

The Court further stated that “motivation” is relevant in “determining whether the skilled person has good reasons to pursue ‘predictable’ solutions or solutions that provide ‘a fair expectation of success’”. The Court agreed with Teva that there was compelling evidence in support of “motivation”, namely reducing dosing frequency and the fact that a more convenient dose regime would improve compliance (see paragraph [52]). 

The Court also assessed if certain properties of quetiapine (e.g. dose size, solubility, partition coefficient, metabolism and duration of action) would have de-motivated the skilled person from trying a sustained release formulation of the drug. The Court held that these properties did not teach away from a sustained release formulation, and stated that the skilled worker would not have viewed them as were "lions in the path”, but rather "paper tigers". (paragraph [56]).

The Court stated that, the prior art, first motivated the skilled person to find the solution of the ‘944 patent - namely, to decrease dosing frequency and the avoidance of dose dumping, and secondly clearly taught that sustained release formulations were commonly used to achieve this purpose, where HPMC being the most commonly used gelling agent.

The Court thus concluded that it was more or less self-evident to try to obtain a sustained release formulation of quetiapine using HPMC, and that the person skilled in the art would have has a fair expectation of success.

Links to decisions: 

http://decisions.fct-cf.gc.ca/en/2013/2013fc245/2013fc245.html (50 mg strength tablets)

http://decisions.fct-cf.gc.ca/en/2013/2013fc246/2013fc246.html (Same reasons for 150, 200, 300 & 400 mg strengths)

By Poonam Tauh

5 (More) Prior Art Search Tips

The always-informative Patently-O blog recently posted an article titled “10 Secrets to Locating Non-Patent Prior Art.” We thought this was a good opportunity to share a few of our own tips for searching prior art. To complement the above article, we will concentrate on more conventional searching techniques using databases such as patent databases.

1. Set a goal 

Is it an invalidity search, a patentability search, or a freedom to operate search? Should the search be exhaustive, exhaustive within a certain field, or simply limited in time or cost? Define a number of search sub-tasks to complete, and budget your time for each sub-task. It likely goes without saying that a little planning goes a long way.

2. Scout out search terms by numbers alone 

This trick will help you to determine what you’re up against when running complex keyword/classification database queries. Start with a list of keywords (including synonyms) and classifications. Build query “atoms” using the list and query each atom individually and then in pairs. For example: Atom “A”: “toaster” returns 12,208 records from a database containing 86,619,634 total records, or 0.0141%. Atom “B”: “butter or jam or spread” returns 1,801,994 records from the same database, or 2.0804%. This shows that Atom “A” is much more specific than Atom “B” and should be treated as a limiting factor. But this is only part of the story. If a pair of atoms is unrelated, the expected number of documents returned by a query for both atoms is given by multiplying the percentages of records returned. For the above example, we would thus expect a query for “toaster AND (butter or jam or spread)” to return 0.0003% of all records, or 254 records. However, the query “toaster AND (butter or jam or spread)” actually returns 1,689 records, which suggests that these two terms are strongly (positively) correlated. The higher the ratio of actual records to expected records, the stronger the correlation. This can be used to identify terms that go together strongly, or that are rarely encountered together.

3. Use random sampling to gauge the effectiveness of a search query 

Patent databases are closing in on 100 million entries, and even a well-constructed query can return a large number of irrelevant results. You can estimate the effectiveness of a large query without reviewing every single document by randomly choosing a much smaller subset for review. The proportion of relevant results in the subset will be roughly the same as the proportion of relevant results overall, and a higher proportion means a better query. What size should your sample be? The Statistics 101 answer is “as big as you can make it,” followed by a set of precise formulas for various situations. You might choose, as a rule of thumb, a sample size of at least 30 documents, at least 50 documents, or a proportion such as 5% to 10% of the total number of results.

4. Follow forward and backward citations, not just by one degree but by multiple degrees

According to this 2011 article by K. Itakura and G. Shlomo, the average degree of separation between two related patents is 6, while the average distance for a random pair of patents is 15. This suggests that searching within 6 degrees of separation will return some (but not all) related patents. However, the number of patent documents within 6 to 13 degrees of separation of a given “starting” patent is typically very large. Therefore, the recommended approach is to compile a list of patents which fall within X degrees of a “starting” patent, and then search this list using keywords, classifications, etc. This heuristic has application to both patent documents and non-patent academic literature.

(Speaking of citation networks, Amberscope is currently offering a free trial tool for visualizing patent citation networks.)

5. Engage the community 

For invalidity searches, Google Patents and StackExchange have teamed up to provide a forum which is intended to allow users to ask others to provide prior art on a particular patent. As well, companies such as Article One Partners allow you to put up a $5,000 bounty for prior art relevant to a particular patent.

By Michael Maskery

Sometimes Deciding To Not Make a Decision is The Best Decision Re: Federal Court decision (2013 FC 141)

In a decision released last month, Judge Snider illustrated that sometimes electing to not make a decision is in fact the best decision.

A link to the public reasons for judgment can be found at
http://decisions.fct-cf.gc.ca/en/2013/2013fc142/2013fc142.html

BACKGROUND:

GLEEVAC is a patented drug sold by Novartis Canada as a treatment for chronic myeloid leukemia. Canadian Patent No. 2,093,203 is a patent listed in relation to this drug on the “Patent Register”.

In order to sell generic versions of GLEEVAC, separately Teva and Apotex applied to the Minister of Health for a Notice of Compliance (NOC).  In the application for the NOC, any patent listed in the “Patent Register” with respect to the drug must be address by either:

“• stat[ing] that it accepts that the NOC will not issue until the patent expires (s. 5(1)(a)); or
 • alleg[ing] that... the patent is not valid...”

The above declaration is made in the application for a NOC by marking the appropriate box on “Form V: Declaration Re: Patent List” (See paragraphs 12 and 13 of the decision).

Initially, both Teva and Apotex checked the box on Form V accepting that the NOC will not issue until the patent expires. Both Teva and Apotex submitted new Forms V alleging the patent was invalid and as a result Novartis was served with Notice of Allegations (NOAs) detailing the reasons of invalidity.

Novartis took the position that “the change of the Form Vs was not permitted by the scheme of the PM (NOC) Regulations; in Novartis Canada’s view, the NOAs are invalid.” (See paragraph 18 of the decision)

Both Teva and Apotex also sought to have the patent declared invalid under s.60(1) of the Patent Act in Impreachment Actions before the Federal Court.  The patent in question was found to be valid and the allegations of invalidity raised in each of the NOAs not justified (See paragraph 7 of the decision).

As noted in paragraph 4 of the decisions, the Impreachment Actions and the Prohibition Applications were consolidated.

DECISION:

This decision only addresses issues raised by the Prohibition Applications, namely

1. Are the Teva and Apotex proper NOAs; and
2. If the NOAs are proper, are the allegations described therein justified?

(See paragraph 6 of the decision).

With respect to question 2 above, as discussed in the Impreachment Actions, the allegations were not justified. The decisions with respect to the Impeachment Actions are discussed at GLEEVEC UTILITY BLOG.  

The question Judge Snider, in my mind, rightly elected not to address in this decision was, in a nutshell, does the PM(NOC) Regulations permit the amendment of a Form V to change an election? (See paragraph 28 of the decision).

Judge Snider’s reasons for not addressing this issue are compelling and are detailed in paragraphs 30 and 31 of her decision.

In particular, Judge Snider noted that “in light of [her] determination that the allegations of invalidity made by Apotex and Teva [were] not justified, the question is not dispositive.”  Judge Snider further indicated that she did “not think that it is a wise use of judicial resources to express what would be only obiter on this important question of statutory interpretation.”

In view of the high likelihood of appeal,  Justice Snider felt that ”[b]y wading into this legal question –which has become purely academic – [she] would not be assisting either the parties before [her] or the Court of Appeal.”


By: Claire Palmer

A Question of Utility re: The Federal Court decision (2013 FC 141)

The Federal Court released a decision (2013 FC 141) last month affirming the validity of the patent covering the active ingredient of GLEEVEC (Canadian Patent No. 2,093,203).

GLEEVEC is a drug effective in the treatment of chronic myeloid leukemia (CML), the active ingredient of which is imatinib mesylate, an inhibitor of the tyrosine kinase ABL kinase. As noted in paragraphs [53] and [54] of the decision, mutant forms of this kinase had been linked to CML. 

The patent at issue disclosed a genus of novel N-phenyl-2-pyrimidine-amine derivatives which included imatinib mesylate, processes for preparing the disclosed compounds, pharmaceutical compositions and therapeutic uses thereof.  This subdividing of subject matter is reflected in the claims of the patent.  As noted in paragraphs [86] and [108] of the decision, the claims of the application fell into one of four categories, namely compound claims; pharmaceutical composition claims, process of making the claimed compounds and therapeutic use claims. 

The compound claims described novel compounds in terms of chemical formula only.  Three of the four pharmaceutical composition claims specify specific indications, i.e. for treatment of tumors.  The use claims include language such as “use in the chemotherapy of tumours”. (See paragraph [108]) 

The key issues addressed in this decision include utility/promise of the patent and sufficiency of disclosure.

Utility and Promise of the Patent

In order to be patentable, an invention must have utility and this utility must be demonstrated or soundly predicted at the Canadian filing date. The Federal Court summarized the three requirements of sound prediction and further stated at paragraph [164] that

Sound prediction is not a free standing statutory requirement. Rather, it is a way of showing that an    invention is useful when the invention has not been directly demonstrated to work. Its introduction into Canadian law was not, as I understand it, to give a crushing hammer to those who challenge patents. [emphasis added]

In addition, the Federal Court noted that an invention which fails to meet the promise of the patent will lack utility and, as such, utility is evaluated against this promise (see paragraph [169]). The promise of the patent is “what the specification promises that it will do” (paragraph [165]).

The promise of ‘203 patent was a point of contention in the present case. The Plaintiffs argued that the promise included specific in vivo therapeutic effect for all claims – i.e. that every claim must have the same utility regardless of the fact that, for example, the compound claims included no language relating to a therapeutic effect.  The Patentee argued that the promise was dependent on which claims were assessed, namely for the compound claims the promise was that they were selective kinase inhibitors, for the use claims the promise was specific therapeutic effects (see paragraph [173]).

The Federal Court rejected the Plaintiffs argument and essentially agreed with the Patentee, stating at paragraph [194]:

For these reasons, I conclude that the promised utility would be as follows:

1. For Claims 1 to 39, the promise is that the compounds will selectively inhibit PKC, PDGF R or ABL.  
2. For Claims 45 to 48, the patent provides the reader with a specified promise of in vivo utility: that a compound included in Claims 1 to 39 can be used to treat atherosclerosis (Claims 45 and 48) and for the “chemotherapy of tumours” (Claims 46 and 47). In my view and in the opinion of the experts, this would incorporate the notion of in vivo efficacy – either demonstrated or soundly predicted (see, for example, Dr. Van Etten at 18T1602). 
3. For Claim 44, the utility is to provide a process to make the claimed compounds.

The Federal Court further found that, as of the filing date of the patent, the utility of a number of the claims (i.e. claims 5, 7, 29, 44 and 46) had been demonstrated or could be soundly predicted.

In particular, the Federal Court found that based on in vitro testing the utility of the compounds of a subset claims as selective kinase inhibitors was demonstrated, the utility of the compounds of a second subset of claims as selective kinase inhibitors could be soundly predicted. While the utility of all compounds in the broadest claims was neither demonstrated nor soundly predicted (see paragraph [244]).

The utility of the use claims as it relates to the treatment of tumours, including CML was found to be soundly predicted. 

Sufficiency of the Disclosure

As noted in the recent Supreme Court case that saw the patent covering Viagra invalidated, “[a]dequate disclosure in the specification is a precondition for the granting of a patent”. (See paragraph [336] of this decision).

Using the framework set out by the Supreme Court, the Federal Court looked to answer the following questions:
“(a) What is your invention?
(b) How does it work?
(c) Having only the specification, can the person of ordinary skill in the art produce the invention using only the instructions contained in the disclosure?” (paragraph [344]).

In order to answer the above questions, the Federal Court defined the “nature of the invention”.  Examining the specification as a whole the Federal Court found “the essential link is the invention of a class of compounds, each one of which can selectively inhibit certain kinases”. (see paragraph [351]).

The Federal Court further found that from the specification a worker skilled in the art could produce the invention.

The second question was not at issue and therefore not addressed in this decision.

As noted in paragraph [387], in the Viagra, “the Supreme Court identified the “key issue” with respect to s. 27(3) disclosure as follows:

As a matter of policy and sound statutory interpretation, patentees cannot be allowed to "game" the system in this way.”

The Federal Court found that this was not an issue in this case, indicating that they were “satisfied that the patentee did not “game” the system” (see paragraph [387]).  In particular, “information was not hidden for the public”. (see paragraph [361]).   

This case is nicely distinguished from the Viagra case and hopefully is indicative of adoption by the Courts of a reasonable approach to determining sufficiency of disclosure.

The decision can be found at the following link:
 http://decisions.fct-cf.gc.ca/en/2013/2013fc141/2013fc141.html


By: Claire Palmer

Intellectual Property Due Diligence (Part 2)

This is the second part of a two part series by Dr. Euan Taylor. Read the first post, Intellectual Property Due Diligence - The Basics (Part 1), for more information.

How much time and money you need to spend on investigating an IP portfolio is going to depend on many factors. Amongst these, the amount of time available and the value of the IP are among the most obvious considerations.

Due diligence can be anything from a cursory look-and-see, to an extensive process that includes preparing legal opinions and interviewing inventors and authors. For convenience, due diligence can be broken down into stages, all of which are infinitely flexible in scope and depth to reflect the nature of the IP in question and any budgetary and time constraints. Some brief suggestions of what may be included in some of these stages are set out below:

Stage 1

Carry out a cursory review of the online resources to see who is shown as the real owner of the IP, whether there are pending deadlines, and whether any applications are pending, issued, or expired. Search for any litigation or other disputes involving the IP. This is really the bare minimum that should be done before pursuing serious negotiations. The results of Stage 1 can be used to prioritize any further work. For some transactions the due diligence process never gets beyond this preliminary stage.

Stage 2

Address any issues identified to date. Review all relevant documentation to ensure that the IP owner has good and clear title to the IP and is free to sell or license it. Review the terms of any licenses for limitations on scope, representations and warranties, reservations of rights, and permissions that may have to be obtained to proceed with the transaction. Have foreign agents confirm the status and ownership of rights in their own jurisdiction. Consider the need for any preliminary assessments or legal opinions on scope, validity and freedom to operate.

Stage 3

Address any issues identified to date. Prepare any necessary legal opinions. Review laboratory notes and interview all inventors to ensure that the chain of title takes account of all parties who may have rights in the IP.

Stage 4

Address any outstanding issues. Take any remedial steps, such as challenging any conflicting third party rights, obtaining supplementary assignments, correcting any errors on the record, and obtaining any necessary consents for the transaction.

Due diligence is an organic process and the content and focus of the work will evolve depending on what surfaces as investigations proceed. Good communication between professional advisors, technical personnel and business management is critical to the efficiency and effectiveness of the due diligence process. IP is a very complex area of law and this article only touches the surface of some issues that may arise. You should always seek qualified professional assistance before making any decisions.

By Euan Taylor

Euan Taylor is a lawyer, patent agent and trade-mark agent and is based in MBM’s Vancouver office. He has wide experience of IP due diligence for a range of commercial transactions and can be reached at etaylor@mbm.com or at 604-239-0271