Abbott Laboratories v. Canada (Health)

Abbott Laboratories v. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2008-12-11
Neutral citation
2008 FC 1359
File numbers
T-135-07
Notes
Reported Decision
Decision Content
Date: 20081211
Docket: T-135-07
Citation: 2008 FC 1359
BETWEEN:
ABBOTT LABORATORIES and
ABBOTT LABORATORIES LIMITED
Applicants
and
THE MINISTER OF HEALTH and
SANDOZ CANADA INC.
Respondents
PUBLIC REASONS FOR ORDER AND JUDGMENT
(Confidential Reasons for Order and Judgment issued December 8, 2008)
HUGHES J.:
[1] This is an application made by Abbott Laboratories and Abbott Laboratories Limited (collectively Abbott) under the provisions of section 6 of the Patented Medicines (Notice of Compliance Regulations), SOR 93-133 as amended (PMNOC Regulations) to prohibit the Respondent Minister of Health from issuing a Notice of Compliance to the Respondent Sandoz Canada Inc. until the expiry of Canadian Letters Patent Number 2,386,527 (’527). For the reasons that follow, I find that the allegations as to invalidity are justified and that the allegations as to non-infringement are not justified. The application is dismissed with costs to Sandoz.
THE PARTIES AND PROCEEDINGS
[2] The Applicant Abbott Laboratories owns the ’527 patent and can be referred to as the patentee. The other Applicant Abbott Laboratories Limited is a Canadian subsidiary of Abbott Laboratories and has regulatory approval (NOC) from the Minister of Health to sell in Canada a drug containing clarithromycin as an antibiotic which it does under the name BIAXIN XL. The two companies are referred to as “first parties” in the PMNOC Regulations.
[3] The Respondent, Minister of Health is charged with certain duties under the PMNOC Regulations and the Food and Drug Act, R.S.C. 1985, c. F-27 as amended and its Regulations including the issuances of Notices of Compliance (NOC) to those applying to the Minister for approval to sell certain drugs in Canada. The Minister was not represented at the hearing of this proceeding.
[4] The other Respondent Sandoz Canada Inc. is what is commonly called a “generic” drug company and is referred to as a “second person” in the PMNOC Regulations. Sandoz applied to the Minister for an NOC to sell a drug product containing clarithromycin in Canada using an Abbreviated New Drug Submission (ANDS) which meant that it simply referenced the previous NOC granted to Abbott thereby limiting greatly the amount of testing and technical date that it was required to submit. On the other hand, Sandoz was required to engage the PMNOC Regulations under which Abbott had listed a number of patents including the ’527 patent.
[5] In accordance with the PMNOC Regulations, Sandoz served on Abbott on or about December 8, 2006 a Notice of Allegation, alleging, among other things, that claim 5 of the ’527 patent was invalid for a number of reasons and that the claim would not be infringed by Sandoz. Abbott instituted this present proceeding by filing a Notice of Application on January 22, 2007, in which it requested that the Minister be prohibited from issuing an NOC to Sandoz until the expiry of the ’527 patent.
MOTION TO STRIKE
[6] Just a few days before the hearing of this proceeding was scheduled to begin, the Applicants filed a motion to strike certain portions of Sandoz’s Memorandum of Fact and Law and for an order prohibiting Sandoz from relying on prior art references other than what were identified as documents 62 and 65, or “evidence relating thereto” in support of its allegations that claim 5 of the ’527 Patent was invalid for obviousness and for anticipation. The motion was to be heard at the opening of the hearing.
[7] The basis for the Applicants’ motion was that in Sandoz’s Notice of Allegation it placed specific reliance only on documents identified as 62 and 65 when alleging invalidity of claim 5 thus, the Applicants assert, Sandoz cannot go beyond reliance upon those two documents in supporting its allegation in evidence and in argument. Reliance is placed on decisions such as ABHassle v. Canada (MNR) (2000), 7 C.P.R. (4th) 272, [2000] F.C.J. No. 855 (FCA) at paragraph 17 where the Federal Court of Appeal said: “…the detailed statement must be such as to make the patentee fully aware of the grounds…”
[8] Sandoz argues that the Applicants were fully aware of the grounds, they received Sandoz evidence without complaint or moving to strike, the Applicants cross-examined upon that evidence without complaint, the Applicants led evidence of their own on the matters addressed by Sandoz in its evidence without complaint. The written argument of the Applicants addresses the evidence and argument of Sandoz.
[9] When asked the Applicants why they waited so long to bring this motion and why no earlier objection had been raised, Applicants’ counsel could only point to the Reasons of the Federal Court of Appeal in Aventis Pharma Inc. v. Mayne Pharma (Canada) Inc. (2005), 38 C.P.R. (4th) 1, 2005 FCA 50, at paragraph 16 where that Court said that such motions should preferably be brought before the hearing judge, but added that it was not wrong for a motions judge to deal with the matter. It said at paragraph 16:
16 Although this Court has stated in unequivocal terms that this type of motion should preferably be deferred to the hearing judge, it has not held, as a matter of principle, that Motions Judges must defer such motions to the hearing judge. Thus, a Motions Judge will not be found to have erred in law if he or she decides to deal with the motion. Whether or not, in a given case, the Motions Judge has made a reviewable error will be dealt with on the basis of the applicable standard of review. I should add that this Court has also made it clear that it will rarely interfere with a Motions Judge's decision to defer the matter to the hearing judge.
[10] This decision does not say that a party must wait to bring a motion such as this before the hearing judge at the outset of the hearing. In fact in the present case the parties were aware for several weeks that I would be the hearing judge yet there was no suggestion that such a motion would be brought.
[11] The Applicants were fully aware of the case they had to meet and did meet that case by cross-examination, by their own evidence and in argument. The merits of the motion, if any, rest only on slender technical grounds. Sandoz has not relied upon documents beyond those listed in its Notice of Allegation where the nature of the attacks on validity of claim 5 was set out. While specific reliance was placed on two documents in the Notice of Allegation, the other prior art was also listed. If the Applicants had felt surprised or disadvantaged the time to object and make a motion was upon receipt of Sandoz evidence, and not to raise the matter a few days before the trial when it is clear that the Applicants were fully prepared on the evidence and in argument to meet the challenge.
[12] The motion was dismissed at the hearing.
WITNESSES AND EVIDENCE
[13] The evidence in this proceeding was, as is usual, provided by way of affidavits and cross-examination transcripts. Since the scope of this proceeding was reduced from the consideration of several claims of several patents to just one claim of one patent, claim 5 of the ’527 patent, the parties, following a request from the Court, filed an amended Record containing only the evidence said to be pertinent to that claim of that patent. As a result the evidence of record includes evidence from the following :
For the Applicants Abbott:
Affidavit of Sonia Atwell, a law clerk employed by Abbott’s solicitors which exhibited, among other matters, the patent at issue, the Notice of Allegation, certain Orders and correspondence. She also testified that Abbott Canada makes tablets known as BIAXIN XL containing clarithromycin as the active ingredient pursuant to a Notice of Compliance granted by the Minister. That notice is not in evidence however it is common ground between the parties that the Notice does not specify any particular crystalline form of clarithromycin.
Atwell was not cross-examined.
Affidavit of Dr. Jerry Atwood a professor of chemistry at the University of Missouri-Columbia. He claimed expertise in crystal growth, crystal engineering, X-ray crystalography and polymer chemistry. No serious challenge to his expertise was raised.
Dr. Atwood was cross-examined.
Dr. Stephen R. Byrn, a professor of medicinal chemistry at Purdue University, Indiana. He claims expertise in solid-state chemistry including polymorphism. His expertise was not seriously challenged.
Dr. Byrn was cross-examined.
Loretta Del Bosco who is employed by Abbott Canada as Director of Regulatory Affairs and Quality Assurance. She does not claim to be an expert.
She was cross-examined.
For the Respondent Sandoz:
Dr. Craig Eckhardt a professor of Chemistry at the University of Nebraska at Lincoln. He claims expertise in crystals and polymorphs. His expertise was not seriously challenged.
Dr. Eckhardt was cross-examined.
Dr. Edward Lee-Ruff a Professor of Chemistry at York University, Toronto. He claims expertise in synthetic and mechanistic organic chemistry. His expertise was not seriously challenged.
Dr. Lee-Ruff was cross-examined.
Dr. Sohrab Rohani a Professor of Chemical and Biochemical Engineering at the University of Western Ontario, London. He claims expertise in the areas of crystallization, crystallization processes, solid state chemistry and polymorphism. His expertise was not seriously challenged.
Dr. Rohani was cross-examined.
Dr. Martyn Brown a PhD. chemist claiming experience in crystallization. His expertise was not seriously challenged. He performed experiments said to be designed to emulate certain prior art.
Dr. Brown was cross-examined.
Dr. Srebai Petrov a research associate at the Department of Chemistry, University of Toronto claiming considerable experience in analytical methods for studying crystalline substances. His experience was not seriously challenged. He analyzed samples prepared by Dr. Brown.
Dr. Petrov was cross-examined.
f. Pamela Christoforakis, a law clerk with Sandoz’s firm of solicitors. She attaches as exhibits copies of the Notice of Allegation and of the prior art referred to in that Notice. She was not cross-examined. No challenge was raised in respect of any of the copies of the prior art documents or the Notice.
[14] Certain portions of the evidence, largely that directed to the processes used to manufacture the Sandoz and Abbott products, were claimed as confidential and, pursuant to an Order of this Court dated March 8, 2007, such documents and evidence relating thereto has been filed with this Court as confidential. Counsel for the parties have endeavoured to restrict their claims to confidentiality to only those documents and materials dealing with processes for producing their versions of clarithromycin.
[15] A consent Order of this Court was issued on April 25, 2007, wherein Sandoz was required to disclose to Abbott certain information, including information that Sandoz provided to the Minister in respect of its product. Included were such documents as would be contained in what is called a Drug Master File (DMF) and samples of any product as supplied to the Minister. Sandoz complied with this Order, no samples were provided since none had been provided to the Minister.
ISSUES
[16] The parties have restricted themselves to issues involving claim 5 of the ’527 patent only. Those issues are:
Construction of the claim. Are the following allegations as to invalidity justified:
Anticipation; Obviousness?
Are the allegations as to non-infringement justified?
[17] Before addressing these issues it will be useful to provide a brief scientific background drawn from the non-controversial evidence of the experts and exhibits provided by them.
SCIENTIFIC BACKGROUND
[18] The scientific background has to do with solid state chemistry and, as the ’527 patent says in its opening words at page 1, crystal forms of chemical compounds.
[19] Chemical compounds for use as pharmaceuticals generally must be in solution, that is, dissolved in some liquid for administration as a liquid or intravenously or by becoming liquid such as when a tablet or pellet in a capsule dissolves in the fluids of the stomach or intestine. Once dissolved the chemical has no particular structure, it is a molecule to be found together with other molecules in the liquid environment.
[20] In solid form, such as in a tablet or pellet, before swallowed the pharmaceutical may, depending on a variety of factors assume various forms or no form at all. An amorphous form means that there is no particular regular form assumed by the material. A crystalline form means that the molecules are in a regular ordered arrangement in a lattice or three dimensional patterns. The same molecule may assume a variety of crystalline forms depending on a variety of factors such as the nature of the molecule, how the substance was prepared, stored or handled and, if prepared by drying, the heat, pressure and time of drying among other matters. A polymorph is a molecular material that can crystallize in a variety of different forms.
[21] As to crystals in particular, it is known that the same molecule can exhibit different properties when it assumes different crystal structures, coal, graphite and diamonds, all of which are carbon crystals are used as common examples of these differing properties.
[22] Identification of a particular crystal structure can rarely be done by eye or touch. Instead a variety of testing techniques are commonly used. Three common techniques are powder x-ray diffraction (PXRD), infra-red (IR) and differential scanning calorimetry (DSC). Each technique produces graphical data which can be read and analyzed by persons skilled in the art. Important identifying features in the graph are noted in respect of samples tested and compared with known graphical features for known crystal forms of the molecule. If they match, then skilled persons recognize the sample as being a known crystal form. If they do not match, then probably a hitherto unknown or previously unidentified form may be present. There is no standard protocol for naming known forms of a crystal structure or new ones as they become identified. Often the first form of a particular molecule to become identified is simply called Form I, the next Form II and so forth. The Forms are related to the identifying characteristics observed from graphs produced by tests such as PXRD or IR or DSC.
[23] In performing a test known as PXRD the sample being tested is prepared in powder form and spread on a flat surface. X-Rays are impringed on the sample in the shape of a cone emanating from the outlet of the X-Ray which is essentially a point. The angle of the outside of the cone measured against the direction in which the x-rays are emanated is called two theta (2 θ). A graph of the scatter of the x-ray beams bouncing off the sample is produced which shows various peaks corresponding to particular ways that the x-rays are scattered. Those peaks vary in intensity depending on how much of the material being studied is present in the sample. Sometimes, the sample tested includes a variety of materials in which case the peaks created by one material may be masked by peaks created by another material. A skilled person will read the graph or, nowadays, a computer may be used, and the important peaks identified. A particular crystal form of a material may be identified by the peaks created by the PXRD technique. Thus it is common scientific language to say something like Form III of chemical x is identified using PXRD with 2 θ values of (say) 2.2, 4.3, 7.8, 9.2 and 15.7. Another sample tested the same way which exhibits the same peaks is said to be Form III also.
[24] In the present case we are dealing with crystalline forms of a pharmaceutical chemical, a molecule known as clarithromycin. The ’527 patent discusses crystalline forms which Abbott has chosen to call Form I and Form II. There is reference elsewhere in the evidence to another form identified as Form 0. The ’527 patent provides graphs showing the result of testing Form I and Form II by each of PXRD, IR and DSC. The claims of the ’527 patent however speak only of Form I and clarithromycin in Form I substantially free of Form II and in identifying Form I the claims speak only of the identification provided by one of those techniques RXRD and the 2 θ values detected at 8 peaks, using recorded figures, at 2 θ values, 5.2, 6.7, 10.2, 12.3, 14.2, 15.4, 15.7 and 16.4 (rounded off).
THE ’527 PATENT – CLAIM 5
a) General
[25] The ’527 patent is the only patent now at issue. Originally several more patents were involved in this application. The parties have reduced the number of patents to this one and the only claim of that patent at issue is claim 5.
[26] The application for the ’527 patent was filed with the Canadian Patent Office on July 25, 1997 which means that the patent is governed by the post October 1, 1989 and, in particular, the post October 1, 1996 version of the Patent Act, R.S.C. 1985, c. P-4.
[27] The application claims priority from a similar application filed in the United States Patent Office on July 29, 1996. The Canadian application was laid open for public inspection on February 5, 1998. The ’527 patent was ultimately issued and granted to Abbott Laboratories on May 27, 2003. The patent will endure for a term of 20 years from its Canadian filing date that is until July 25, 2017, unless earlier held to be invalid in an action (not this proceeding) brought for that purpose in this Court.
b) Description of the patent
[28] The descriptive portion of the ’527 patent comprises the first seventeen pages (the last two are numbered 15a and 15b) together six graphs at the end identified as Figures 1a, b and c and 2 a, b and c. Figure 1a is a graph illustrating a PXRD graph of Form I clarithromycin, 1b is an IR graph, and 1c is a DCS graph. Figures 2 a, b and c are similar graphs for Form II clarithromycin. The descriptive position of the ’527 patent is similar in many respects to that of another Canadian Patent 2,258,606 (’606) which patent has been considered in other NOC proceedings in the Court and the Federal Court of Appeal. The ’606 patent has claims directed to Form II clarithromycin while the claims of the ’527 patent are directed to Form I clarithromycin. Both patents claim priority from the same United States patent application, 08/681, 723 filed July 29, 1996. The application for the ’527 patent was filed directly with the Canadian Patent Office on July 25, 1997 whereas the application for the ’606 patent was filed under the provisions of the Patent Co-Operation Treaty (PCT) on July 25, 1997 and entered the “national phase” in Canada on December 16, 1998. For purposes of considering construction both were laid open for public inspection on February 5, 1998 and for purposes of anticipation and obviousness, both have a “claim date” of the claimed priority filing date of the Untied States application, July 29, 1996. I set out this identity because other Courts have considered the ’606 patent.
[29] The ’527 patent at issue begins with a description of the technical field which description includes both Form I and II:
Technical Field
This invention relates to compounds having therapeutic utility and to methods for their preparation. More particularly, the present invention concerns the novel compounds 6-O-methylerythromycin A crystal Form I and Form II, a process for their preparation pharmaceutical compositions comprising these compounds and methods for use as a therapeutic agent.
[30] Following that the ’527 patent acknowledges that clarithromycin and its use as an antibiotic in humans form the background of what is later discussed as being the invention. In other words, clarithromycin and its use is prior art. It says (without reproducing the picture of the molecule):
6-O-methylerythromycin A (Clarithromycin) is a semisynthetic microlide antibiotic of formula
…
Which exhibits excellent antibacterial activity against gram-positive bacteria, some gram-negative bacteria, anaerobic bacteria, Mycoplasma, and Chlamidia. It is stable under acidic conditions and is efficacious when administered orally. Clarithromycin is a useful therapy for infections of the upper respiratory tract in children and adults.
[31] Page 2 of the ’527 patent sets out a summary of the alleged invention, in brief, it says that the inventors have discovered that clarithromycin can exist in and at least two crystal forms which they call Form I and Form II, that these forms have an “identical spectrum of antibacterial activity” but that Form I dissolves more quickly. It is stated that Form I exclusively can be found when clarithromycin is recrystallized from a solution containing certain solvents. In other words, Form I and Form II have the same antibacterial properties, Form I dissolves more quickly:
Summary of the Invention
We have discovered that 6-O-methylerythromycin A can exist in at least two distinct crystalline forms, which for the sake of identification are designated “Form I” and “Form II”. The crystal forms are identified by their infrared spectrum, differential scanning calorimetric thermogram and powder x-ray diffraction patterns. Form I and Form II crystals have an identical spectrum of antibacterial activity, but Form I crystals unexpectedly have an intrinsic rate of dissolution about three times that of Form II crystals. Investigations in our laboratory have revealed that 6-O-methylerythromycin A when recrystallized from ethanol, tetrahydrofuran, isopropyl acetate, and isopropanol, or mixtures of ethanol, tetrahydrofuran, isopropyl acetate, or isopropanol with other common organic solvents result in exclusive formation of Form I crystals, not identified hitherto before.
[32] The summary goes on at page 2 of the ’527 patent to say that “Drugs currently on the market” utilize Form II crystals. It is asserted by Abbott and not disputed by Sandoz that this is a reference to Abbott’s BIAXIN product (not the later product BIAXIN XL) and that while BIAXIN contained essentially only Form II as an active ingredient, the public was not aware as to what the crystal form was. It says:
Drugs currently on the market are formulated from the thermodynamically more stable Form II crystals. Therefore, preparation of the current commercial entity requires converting the Form I crystals to Form II. Typically this is done by heating the Form I crystals under vacuum at a temperature greater than 80oC. Therefore, the discovery of a novel form of 6-O-methylerythromycin A which can be prepared without the high temperature treatment results in substantial processing cost savings. In addition, the favourable dissolution characteristics of Form I relative to Form II increases bioavailability of the antibiotic and provides significant formulation advantages.
[33] What is being said is that Form I is cheaper to make and, because it dissolves more quickly, can be more advantageously formulated into a drug.
[34] The summary at page 2 of the ’527 patent describes the characteristics of Form I crystals with reference to the 2 θ values obtained by the PXRD technique:
Accordingly, the present invention in its principle embodiment provides a novel crystalline antibiotic designated 6-O-methylerythromycin A Form I. This novel crystalline antibiotic may be characterized by peaks in the powder x-ray diffraction pattern having the following 2 θ values (not repeated here, they are the same as set out in claim 1 which is repeated in full subsequently in those reasons).
[35] The summary distinguishes between Form I and Form I “substantially free” of Form II.
In another embodiment, the present invention provides a novel crystalline antibiotic designated 6-O-methylerythromycin A Form I substantially free of 6-O-methylerythromycin A Form II. This novel crystalline antibiotic may be characterized by peaks in the powder x-ray diffraction 2 θ (same values as in claim 1).
[36] The summary of the ’527 patent at page 2 and over to page 3 states that the alleged invention also includes pharmaceutical compositions including Form I, to a method of treating mammals by administering Form I and to a process of making Form I.
The present invention also provides pharmaceutical compositions which comprise a therapeutically effective amount of 6-O-methylerythromycin A Form I in combination with a pharmaceutically acceptable carrier and such compositions for use in the treatment of bacterial inventions or in the preparation of an antibiotic medicament.
The invention further relates to a method of treating bacterial infections in a host mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of 6-O-methylerythromycin A Form I.
In another embodiment, the present invention provides a process for preparing 6-O-methylerythromycin A Form I comprising…
[37] In the process described at page 3 the steps of drying the crystals out of solution is described as being carried on between ambient temperature (later described at page 8 as being about between 20oC to about 25oC) and about 70oC. At lines 19 and 20 on page 3 the patent says:
(d) drying 6-O-methylerythromycin A is isolated in step (c) at a temperature of between ambient temperature and about 70oC to form 6-O-methylerythromycin A Form I.
[38] In what is described as a “preferred route” at pages 7 to 9 of the patent the drying step is more particularly described:
For purposes of this specification, ambient temperature is from about 20oC to about 25oC. Crystalline 6-O-methylerythromycin A is then isolated, preferably by filtration, and the wet solid is converted to 6-O-methylerythromycin A Form I by drying in a vacuum oven at a temperature of between ambient temperature and about 70cC, preferably from about 40 to about 500C and a pressure of between about 2 inches of mercury and atmospheric pressure to remove any remaining solvent.
[39] The Form I clarithromycin is said at pages 9 to 12 as being capable of formulation into a pharmaceutical composition in solid or liquid form:
The present invention also provides pharmaceutical compositions which comprise 6-O-methylerythromycin A Form I formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions may be specially formulated for oral administration in solid or liquid form, for parenteral injection, or for rectal administration.
…
Solid dosage forms for oral administration include capsules, tablets, pills, powder and granules.
…
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs.
[40] The reference to liquid forms is peculiar because a crystal such as Form I is no longer a crystal once it is in solution, it loses its crystalline identity. There can be no liquid dosage forms which includes Form I crystals. When asked about this at the hearing Abbott’s counsel had no explanation. Perhaps it was an overzealous or careless patent draughtsman.
[41] The dosage levels for administration are described at page 12 and 13 as levels that “may be varied” depending on several conditions and that it is “within the skill of the art” to start with lower doses then increase the level:
Actual dosages levels of active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated, and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved.
Generally dosage levels of about 1 to about 1000, more preferably of about 5 to about 200mg of 6-O-methylerythromycin A Form I per kilogram of body weight per day are administered to a mammalian patient. If desired, the effective daily dose may be divided into multiple doses for purposes of administration, e.g. two to four separate doses per day.
[42] Nowhere is it set out whether the fact that Form I is the crystalline form used to do the formulations of the pharmaceutical composition makes a difference or is in any way different from, for instance, Form II formulations. The “significant formulation advantages” promised at page 2 are not described or exemplified anywhere.
[43] The intrinsic dissolution rate for Form I in comparison with Form II as promised at page 2 is, however, exemplified in Example 4 at page 19 of the ’527 patent:
Example 4
Dissolution Rates of 6-O-methylerythromycin A Forms I and II
Dissolution studies were carried out at 60 rpm in 300mL of 0.05 M phosphate buffer at 37oC using a constant surface area (13/32”diameter) drug compact. Aliquots were removed periodically and assayed directly by HPLC (5cm x 4.6mm 3μ ODS-2 “Little Champ” (Regis) column; 50:50 acetonitrile-0.05 M pH 4.0 phosphate buffer mobile phase; 1.0 mL/min flow rate). As shown in Table 1. 6-O-methylerythromycin A Form I has an intrinsic rate of dissolution about three times grater than Form II.
[44] Nowhere, however, does the patent show what advantage, if any, this increased rate gives. Both Form I and Form II dissolve. Form II is acknowledged at page 2 of the patent to be the active ingredient in a commercial product. Thus it is reasonable to infer that Form II is sufficiently soluble for commercial use. What then is the advantage of increased solubility? It is not stated.
c) Claim 5
[45] Claim 5 reads as follows:
5. The use of 6-O-methylerythromycin A Form I according to claim 1 or 2 in the treatment of bacterial infections in a host mammal.
[46] Claims 1 and 2 referred to in claim 5 reads as follows:
1. 6-O-methylerythromycin A Form I characterized by peaks in the powder x-ray diffraction pattern having the following 2 θ values: 5.2o±0.2, 6.7o±0.2, 10.2o±0.2, 12.3o±0.2, 14.2o±0.2, 15.4o±0.2, 15.7o±0.2, and 16.4o±0.2.
2. 6-O-methylerythromycin A Form I characterized by peaks in the powder x-ray diffraction pattern having the following 2 θ values 5.16o±0.2, 6.68o±0.2, 10.20o±0.2, 12.28o±0.2, 14.20o±0.2, 15.40o±0.2, 15.72o±0.2, and 16.36o±0.2.
[47] It can be seen that claim 1 differs from claim 2 in that the values for 2 θ are rounded off to one decimal place in claim 1 whereas those values are expressed to two decimal places in claim 2.
[48] Claim 5 can be simplified for purposes of discussing the issues in this proceeding by referring to 6-O-methylerythromycin A simply as clarithromycin and to say simply Form 1 without recitation of the eight 2 θ values.
[49] Thus claim 5 can more cryptically be written as:
“5. The use of Form 1 clarithromycin in the treatment of bacterial infections in a host mammal”
[50] It is common ground between the parties that claim 5 is directed to a particular use of clarithromycin, namely “…treatment of bacterial infections in a host mammal”. It is also common ground that claim 5 covers the use of Form I clarithromycin even where Form I may be mixed with other forms of clarithromycin, for example Forms 0 and Form II.
[51] It is to be noted that claim 1 and 2 are directed only to Form I and do not specify any particular use. They are not at issue in this proceeding.
[52] It is also noted that other claims such as 7 and 8 specify that the clarithromycin Form I be “substantially free” of Form II. Again, these claims are not at issue.
[53] It is further to be noted that claim 5 in speaking of Form I references that Form to be “according to claim 1 or 2” and that claim 1 and 2 identify Form I as that identified by 8 specified values determined by the PXRD technique at 2 θ.
[54] In addressing the points in the construction of claim 5 that are relevant to the discussion at hand one must consider what the late Justice Pumfrey of the English Chancery Court (Patent Division) as he then was, said in Nokia v. Interdigital Technology Corporation, [2007] E.W.H.C. 3077 (Pat.) at paragraph 25, regard must be had to where the “shoe pinches”.
[55] For the purpose of the discussion at hand, therefore, claim 5 can be construed as saying:
“5. The use of clarithromycin, at least some of which is Form I, for the treatment of bacterial infections in a host mammal”.
PERSON SKILLED IN THE ART
[56] The parties are in substantial agreement that, when it is necessary to consider who is a person skilled in the art (POSITA) to whom the ’527 patent is addressed, that person is a chemist or chemical engineer having at least a bachelor level degree and at least three to five years experience in the pharmaceutical industry including substantial experience with crystallization processes.
VALIDITY
a) General
[57] This is a proceeding brought under the provisions of section 6 of the PMNOC Regulations for a determination of several issues including whether Sandoz’s allegations that claim 5 of the ’527 patent is “not valid” is “justified”. The use of the term “not valid” comes from section 5(b)(iii) of the PMNOC Regulations and, as the Supreme Court of Canada (Rothstein J. for the Court) wrote in Apotex Inc. v. Sanofi-Synthelabo Canada Inc., 2008 SCC 61 (Sanofi) at paragraph 17, the inquiry parallels what would otherwise be a defence to an infringement action as referred to in section 59 of the Patent Act.
[58] The Patent Act, section 43(2), in the case of a post October 1, 1996 patent such as the ’527 patent here, provides that a patent shall, in the absence of evidence to the contrary, be valid. In Pfizer Canada Inc. v. Canada (Minister of Health), 2008 FC 11, I reviewed the recent authorities, including two from the Federal Court of Appeal, on the question as to who had the burden of proof as to validity particularly in NOC proceedings such as this, and concluded that a patentee such as Abbott may rely on the presumption of validity however, if the attacking party, Sandoz, has lead reliable evidence, then the Court must weight all the evidence on the usual civil burden of proof, if the matter was then seen to be evenly balanced, the attack on validity fails. At paragraph 33 of that decision, I wrote:
33 If the matter were an ordinary action for, say, infringement of a patent where validity is put in issue, the party challenging validity bears the burden such that, it must put in evidence to support the allegation of invalidity. The patentee may rely on the presumption but only to the extent that the attacking party must lead some reliable evidence to support its allegation. At the end of the day, the Court must weigh the evidence on the usual civil burden of proof (Tye-Sil Corp. Ltd. v. Diversified Products Corp. (1991), 35 C.P.R. (3d) 350 at 357-359 (F.C.A.)). Only if the Court finds the evidence to be "evenly balanced" (a rare event) would the question of burden arises in an ordinary case the party attacking validity, bearing the burden, would fail.
[59] The attacks made as to the validity of claim 5 of the ’527 patent are those of anticipation (lack of novelty) and obviousness (lack of invention). I reviewed these concepts in detail in Eli Lilly Canada Inc. v. Apotex Inc., 2008 FC 142 at paragraphs 127 to 129 citing the Federal Court of Appeal in Imperial Tobacco Ltd. v. Rothmans Benson & Hedges Inc. (1993), 47 C.P.R. (3d) 188, Professor Carl Moy, and Lord Hoffman in Synthon BV v. SmithKlineBeechman plc, [2005] UKHL 59 (Synthon) a decision relied on heavily by Rothstein J. in Sanofi, supra. In brief, anticipation and obviousness are both questions of fact, prior art may be considered in respect of both, but the tests are to be used differently. In anticipation, a single document or, for post October 1989 patents, a single disclosure, is to be considered as it would be been considered by a person skilled in the art as of the relevant date to determine if the claimed invention would have been disclosed and enabled to such a person at that time. If so, the claimed invention was anticipated. With respect to obviousness, if there are differences between what was disclosed, was there room left for a person to make an inventive contribution. If what was not disclosed was something that a person skilled in the art as of the relevant date would have been expected to do without exercising invention ingenuity, hence the claimed invention is obvious.
[60] In the case of a post October 1, 1996 patent such as the ’527 patent the relevant date for consideration of novelty, where a disclosure has been made by someone other than the inventor or person deriving knowledge from the inventor, is the “claim date” which, in the case of the ’527 patent which claims priority from the United States patent application filed July 29, 1996, is that date of filing that United States application (sections 28, 28.1 and 28.2 of the post-October 1, 1996 version of the Patent Act). In respect of obviousness, the relevant date, in this case since no disclosure was made by the inventors or other persons gaining knowledge from the inventors, is also the “claim date”, July 29, 1996 (section 28.3 of the Patent Act, supra).
[61] Chemical patents, including those directed to pharmaceuticals, present particular concerns. Complex molecules are often involved. A prior art disclosure, such as an earlier patent may disclose a particular molecular structure with instruction that, at certain locations other molecules may be added or substituted or left out. Often the reader is left to select from classes or groups of molecules from which those choices may be made. Often the number of possible choices can number in the thousands or hundreds of thousands and more. Where different choices are made the resulting molecules are sometimes referred to as analogues of each other. A subsequent patent may claim one such analogue or a group of them and the Court may be asked if such claim is anticipated or obvious.
[62] Another situation may present itself where the molecular structure can be twisted, when viewed three dimensionally, this way or that. A molecule may be twisted around what are called chiral centres within the structure, and depending upon how many such centres exist in a molecule, there can be several differently twisted versions of the molecule. A mixture of such molecules with equal amounts of each twisted version is called a racemic mixture, and each individual twisted version is often called enantiomer. In Sanofi the Courts had to consider whether the selection of one of these enantiomers was anticipated or obvious.
[63] A third situation is one present in this case. In solution a molecule simply floats around with other molecules in the solution. When the molecules in solution dried out, they may assume one or another crystalline shape. The molecule however, remains chemically the same. The solidified shape of the crystals may vary. Whether the selection of one such crystalline shape was anticipated or obvious is the question here.
b) Prior Knowledge
[64] It is not contested that there was considerable prior knowledge that a person skilled in the art would have had before the “claim date”, July 29, 1996. From the Memoranda and written submissions filed and from statements made by counsel for the parties during the hearing, as well as from what has been set out at pages 1 and 2 of the description of the ’527 patent previously reviewed, at least the following can be accepted as prior knowledge:
1. Clarithromycin and its molecular structure were known
2. The use of clarithromycin in the treatment of bacterial infections in a host mammal such as a human was known. This was the onl