[Ip-health] A US court judgment that is relevant to Novartis case

Tue Mar 27 10:24:19 2007

The blog PatentlyO suggests here that the Pfizer v. Apotex case may
have implications beyond the patentability of salt forms:
http://www.patentlyo.com/patent/2007/03/routine_experim.html

As has been noted, the court held that Pfizer's improvements were
neither "unexpected" nor "surprising."  Pfizer had argued for non-
obviousness on the grounds that the beneficial effect of producing
the salt was "unpredictable," but the court held that even if the
effect is unpredictable, this does not suffice for patentability if
there is a "reasonable expectation of success."

The "reasonable expectation of success" standard could have
implications for the patentability of many minor changes to
previously existing drugs.

Mar 26, 2007
Routine Experimentation -> Obvious

Pfizer v. Apotex (Fed. Cir. 2007).

Norvasc=AE is Pfizer's patented blockbuster drugs for treating
hypertension and angina.  The Court of Appeals for the Federal
Circuit (CAFC) has invalidated Pfizer's patent -- finding it obvious.
Generics are already on the market.

Background: Apotex, a generic manufacturer, filed a notice with the
FDA -- certifying its belief that Pfizer's patent covering Norvasc
was invalid and unenforceable. The trial court upheld Pfizer's patent
and issued an injunction stopping Apotex from making a generic version.

Courts and the PTO: In its appellate opinion, the CAFC began with a
strong repudiation of any reliance on Examiner's findings during
prosecution of a patent: "Our case law consistently provides that a
court is never bound by an examiner=92s finding in an ex parte patent
application proceeding."  Applying this boundary, the panel found
that "it can never be the case that an examiner=92s interim finding of
prima facie obviousness renders the claims of an issued patent prima
facie obvious."

Unpredictably Obvious: Norvasc is amlodipine besylate.  At the time
of the invention, amlodipine was known as was the use of besylate
anions.  Pfizer argued that the results of combining these would have
been unpredictable and therefore non-obvious.  The CAFC disagreed,
finding that unpredictability does not result in nonobviousness.

     [A] rule of law equating unpredictability to patentability,
applied in this case, would mean that any new salt ... would be
separately patentable, simply because the formation and properties of
each salt must be verified through testing. This cannot be the proper
standard since the expectation of success need only be reasonable,
not absolute.

Here, the court found plenty of evidence to believe that a PHOSITA
would have had a reasonable expectation of success.

Obvious to try: A combination can be "obvious to try" but still be
nonobvious.  This is may be true, for instance, in cases where there
are many potential parameters or where the art merely suggests a
=93general approach that seemed to be a promising field of
experimentation.=94 The court distinguished those situations from the
present case -- finding that a PHOSITA would have been able to narrow
the group of potential salt-formers to fewer than 53 anions, which
would be an acceptable number to form "a reasonable expectation of
success."

Routine Experimentation: Start telling your story!!  It is
axiomatically true that patentability is not negated by the manner in
which the invention was made.  The exception, found here, is that
"routine testing" can be considered a reason to invalidate the patent.

     [T]he prior art provided not only the means of creating acid
addition salts but also predicted the results, which Pfizer merely
had to verify through routine testing.

Secondary Factors: On appeal, the CAFC also held that it was an error
to consider Pfizer's switch from a different form of amlodipine to
amlodipine besylate as a secondary factor of obviousness.
Furthermore, comparison of unexpected results must compare the
invention to the closest prior art -- not to the closest commercial
product.

Orange Book Issues: Mylan was first to challenge the patent and
lost.  Under the Orange Book rules, Mylan still qualifies for six-
months as the exclusive generic seller.  Apotex, which won this case,
claims that it also has rights to begin selling a generic version as
soon as the FDA gives its approval. Apotex, however, has not
presented its legal claim.

Expiration: When $2.4 billion per year are at stake, every day
counts.  The patent was set to expire on Sunday, although Pfizer
claimed six additional months of exclusivity based on its testing of
childhood eficacy.

Notes:

     * The patent had previously been upheld by three separate
district courts.

On Mar 27, 2007, at 1:22 AM, chan park wrote:

> --
> [ Picked text/plain from multipart/alternative ]
> fyi - the full decision is available at http://fedcir.gov/opinions/
> 06-1261.pdf.
>
> this decision casts doubt on the validity of all patents and
> pending patent applications relating to converting a drug into a
> "pharmaceutically acceptable" salt form.  in arguing that it was
> obvious to convert amlodipine (the active ingredient) to amlodipine
> besylate, apotex argued that it was well known in the art to
> convert a drug into its salt form in order to improve its
> stability, solubility, hygroscopicity, manufacturability, etc.
>
> in the present case, apotex relied on a 1977 article:  Berge,
> "Pharmaceutical Salts," J. Pharm. Sci. 66(1):1-19 (Jan 1977) to
> show that it was well known in the art to convert a drug into its
> salt form for these reasons.  since the priority date of the patent
> at issue in this case, there have been further advancements in the
> science of salt selection.  for instance, in the gleevec
> opposition, we successfully relied on the following article to show
> that the salt selection process was routine and non-inventive :
>
> Morris, et al., =93An integrated approach to the selection of optimal
> salt form for a new drug candidate,=94 International Journal of
> Pharmacuetics 105 (1994) presented an integrated, three-tiered
> approach to selecting the optimal salt for any given new drug
> candidate.  Starting from a pool of seven possible salts, the
> authors proposed an approach by which the least time-consuming
> experiments were conducted in the first tier, and the more time-
> consuming experiments were conducted as more and more candidates
> were eliminated in the earlier tiers.  Using this approach, the
> authors concluded that the entire salt-selection process could be
> completed within 4-6 weeks or less and easily be adopted into the
> drug development program.
>
> the holding in the pfizer v. apotex case supports the proposition
> that conversion of a drug into a salt form to improve its
> stability, solubility, hygroscopicity, manufacturability, etc will
> essentially always be non-inventive, because such improvements,
> even if real, are very well known in the art, and are neither
> "unexpected" nor "surprising."
>
> this decision is also notable for its rejection of pfizer's proffer
> of evidence to show that it had invested substantial sums of money
> into research and development as a secondary consideration of
> nonobviousness.  the court also implicitly holds that one must
> compare the compound at issue against the "entire range of prior
> art compounds,"  even if not expressly disclosed in the prior art.
>
> this is significant - particularly in india with section 3d -
> because it places the burden on the applicant to show that its
> application represents not only an improvement over the free base
> compound, but over all other derivatives contemplated by the
> disclosure of the free base.  we successfully used this argument in
> the gleevec patent opposition to show that any improvement in
> "efficacy" had to be shown as between b-crystalline imatinib
> mesylate versus other forms of imatinib mesylate, and not the free
> base, imatinib.
>
> happy opposing,
>
> chan
>
> Joana Ramos <joaninha@comcast.net> wrote: http://www.hindu.com/
> thehindu/holnus/006200703251901.htm
>
>
> A US court judgment that is relevant to Novartis case
>
> The Hindu Online
> Business
>
> D Murali
>
> Chennai, March 25: A recent decision of a US court may be relevant
> for a
> case currently on in Chennai court, says Ms Srividhya Ragavan,
> Associate
> Professor of Law, University of Oklahoma Law Center, in a mail sent to
> Business Line. "On March 22, the United States Court of Appeals for
> the
> Federal Circuit, which is the highest court in the US for patent
> appeals, issued a judgment on the same lines as the Indian statute and
> the Chennai Patent office," she explains. Novartis, which has been
> criticised by health activists for challenging Indian patent law in
> Chennai court, is said to be seeking the support of the European
> Parliament's members.
>
> Here's more from Ms Ragavan about the case.
>
> First, the Novartis case, in India.
>
> As many of us are already aware, the Chennai Patent office's
> refusal to
> award patent protection on Gleevac has been challenged by the drug
> maker
> in the High Court. The Chennai Patent office rejected an
> application on
> Gleevac on the grounds that the material sought to be patented by
> Novartis was obvious and hence, unpatentable. An invention has to be
> useful, novel and nonobvious in order to become eligible for patent
> protection. In order to determine whether something is nonobvious, the
> material (sought to be patented) is compared with the existing
> materials
> in the same field of science. If the application material embodies
> adequate levels of skill when compared with the existing state of
> knowledge, then it can be deemed nonobvious.
>
> What does the Indian law on the subject say?
>
> As far as chemical inventions are concerned, Section 3 (d) of the
> Indian
> Patent Act deems a mere discovery of a new form of a known
> substance as
> being obvious and hence, not patentable unless it also results in an
> enhanced efficacy. (What amounts to enhanced efficacy is left to the
> purview of the examiner through patent office guidelines). The statute
> outlines that forms of known compounds like "salts, esters, ethers,
> polymorphs, metabolites, pure form, particle size, isomers,
> mixtures of
> isomers, complexes, combinations and other derivatives" would be
> treated
> as the same substance or just as obvious variations. The Indian Patent
> Act deems that if Chemical A is already known, other forms of
> Chemical A
> like salts, isomers, esters etc., are just considered as different
> forms
> of Chemical A and not as a new invention.
>
> How is that relevant to the Novartis case?
>
> The Novartis application seems to relate to an isomer of an existing
> compound. That is, the active ingredient in Gleevac was known.
> Novartis
> felt that it was the first to invent the isomer of that compound. The
> Chennai patent office felt that it is just another form of an already
> known and existing compound and hence, did not qualify as an
> invention.
> When the atoms of a known compound are arranged differently, we call
> them isomers. Thus, an isomer of Chemical A will have the same
> chemical
> formula although the atoms are arranged differently. (Different
> structure but same formula). Novartis argues that isomers should be
> considered nonobvious over the existing compound.
>
> Now, the US case. What was it about?
>
> Pfizer, a huge pharmaceutical giant filed a suit against Apotex, a
> generic drug maker for infringing its patent on Norvasc. Norvasc is
> used
> to treat hypertension and some forms of angina. The active
> ingredient in
> the drug Norvasc is amlodipine but the ingredient is tinkered with and
> made into acid addition salt form. Thus, Norvasc is a besylate form of
> amlodipine (amlodipine besylate). Besylates are anacid addition salt
> forms of the original chemical. That is, if we assume that Chemical
> A is
> the original compound, Besylate of Chemical A is the salt form of
> Chemical A. In this case, amlodipine besylates is an acid addition
> salt
> form of amlodipine. Pfizer acquired a patent bearing number 4,879,303
> over amlodipine besylate in 1989.
>
> What was the contention of Apotex?
>
> When Pfizer sued for infringement, Apotex alleged that Pfizer's patent
> is invalid because the invention was obvious from Pfizer's own
> previous
> patent on amlodipine. Apotex pointed out that Pfizer was the patent
> owner over amlodipine (US Patent No. 4,572,909) which was issued in
> 1986. Amlodipine besylates, Apotex argued, are just the salt form of
> amlodipine and hence, are just obvious improvements.
>
> What was the decision?
>
> The Federal Circuit agreed with Apotex and held that amlodipine
> besylates was prima facie obvious over amlodipine. It is notable that
> there was no significant or enhanced utility in the besylate form. The
> Federal Circuit ruling merely reiterates an established principle that
> salts of known compounds are deemed to be obvious unless there is an
> unexpected utility or improvement or efficacy.
>
> On the verdict's relevance to India
>
> The principle reiterated by the Federal Circuit is what is already
> present in the Indian statute. Section 3(d) also states the same
> principle - salts, isomers, esters are not inventions but mere
> different
> forms of the same substance. In rare instances, they may be considered
> as inventions if they have an enhanced utility. The burden to prove
> and
> convince an examiner that there is an enhanced utility was clearly on
> Novartis. And, Novartis failed. Having failed its burden, Novartis
> lacks
> sufficient grounds to argue that the Indian statute should be amended.
> If at all, the US Federal Circuit judgment indirectly supports and
> affirms the Chennai patent office decision.
>
>
> --
> Joana Ramos, MSW
> Cancer Resources & Advocacy
> 7303 23rd Ave. NE
> Seattle, WA  98115
> 206-229-2420
> http://ramoslink.info/
>
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