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RECENT FEDERAL CIRCUIT
CASES CONCERNING
PHARMACEUTICAL AND
BIOTECH INVENTIONS
December 2009
Topics to be Covered
1.
Statutory Subject Matter after Bilski
2.
Anticipation
3.
Obviousness
4.
Enablement
5.
Product-by-Process
6.
Double Patenting
Statutory Subject Matter
Prometheus Laboratories v. Mayo Clinic (Fed. Cir.
2009).
The patent claimed methods including:
(a) “administering” a drug that provides 6-TG to a subject;
(b) “determining” the levels of the drug’s metabolites, 6-TG
and/or 6-MMP, in the subject; and
(c) comparing the measured metabolite levels to predetermined metabolite levels, “wherein” the measured
metabolite levels “indicate a need” to increase or decrease the
level of drug to be administered so as to minimize toxicity and
maximize efficacy of treatment.
Statutory Subject Matter
The court framed the issue as whether Mayo’s claims are
“drawn to a fundamental principle or an application of a
fundamental principle.”
The court referred to its “definitive” Bilski test, i.e., that a
process is patent-eligible under § 101 if:
(1) “it is tied to a particular machine or apparatus, or
(2) it transforms a particular article into a different state or
thing”; and
 this transformation must be “central to the purpose of the
claimed process” and not merely “data gathering.”
Statutory Subject Matter
The court found that the claimed method met the “transformation”
prong of Bilski

“When administering a drug such as AZA or 6-MP, the human body
necessarily undergoes a transformation. The drugs do not pass
through the body untouched without affecting it.”

The determining step is also transformative and central to the claimed
methods because “[d]etermining the levels of 6-TG or 6-MMP in a
subject necessarily involves a transformation, for those levels cannot
be determined by mere inspection.”
Statutory Subject Matter
This transformation is not mere “data-gathering” because
“Measuring the levels of 6-TG and 6-MMP is what enables
possible adjustments to thiopurine drug dosage to be detected for
optimizing efficacy or reducing toxicity during a course of
treatment.”
The court also found that the final “mental step” in the claim of
providing a warning based on the results of the prior steps does
not detract from the patentability of the “claimed methods as a
whole.”
Anticipation
In In re Gleave (Fed. Cir. 2009), the court held that a reference need
not disclose an independent use or utility to anticipate a claim
under § 102.
Gleave claimed:
[a] bispecific antisense oligodeoxynucleotide, wherein substantially all of
the oligodeoxynucleotide is complementary to a portion of a gene
encoding human IGFBP-2 and …to a gene encoding human IGFBP-5,
and wherein the oligodeoxynucleotide is of sufficient length to act as an
antisense inhibitor of human IGFBP-2 and human IGFBP-5.
Anticipation
The prior art disclosed:
- a 1400 sequence list of every fifteen-base-long sense
oligodeoxynucleotide in the IGFBP-2 gene;
- the general concepts that antisense oligonucleotides are
preferably between fifteen and twenty-five bases in length;
- that some antisense oligonucleotides may be bispecific (i.e.,
capable of inhibiting “an IGFBP such as IGFBP-2 and/or IGFBP5”); and
- that “[a]ntisense oligonucleotides to IGFBP-2 may be selected
from molecules capable of interacting with one or more” of the
1400 sense oligonucleotides described.
Anticipation
Gleave argued that the prior art provided no guidance to make
particular selections, and no understanding of which of the
targets would be useful, and what the properties of the related
antisense would be.
The Federal Circuit disagreed, noting that precedent “makes clear
that a reference need disclose no independent use or utility to
anticipate a claim under § 102.”
Anticipation
In Amgen v. Hoffman-LaRoche (Fed. Cir. 2009), the Federal Circuit
reviewed the validity of a claim to “[a] pharmaceutical
composition comprising a therapeutically effective amount of
human erythropoietin and a pharmaceutically acceptable
diluent, adjuvant or carrier, wherein said erythropoietin is
purified from mammalian cells grown in culture.”

Roche argued that addition of the source limitation (“purified
from mammalian cells grown in culture”) could not distinguish
the prior art urinary EPO because the EPOs were the same,
regardless of source.
Anticipation
The court held that::

An old product is not patentable even if made by a new process;

But a product may be patentable by reciting source or process
limitations so long as the product is new and unobvious;

Thus, the district court did not err in giving weight to the source
limitation since “by its plain terms,” the patent “claims a product with a
source limitation.”

Moreover, the claimed recombinant EPO with the source limitation
was not anticipated because, compared to natural EPO, it had (1) a
higher molecular weight; (2) different charge; and (3) a different
carbohydrate content.
Anticipation
In Iovate Health Sciences, Inc. v. Bio-Engineered Supplements &
Nutrition, Inc. (“BSN”) (Fed. Cir. 2009), the court addressed the
question of whether an advertisement for a nutritional supplement was
an anticipatory “printed publication” for a claim reciting:

A method for enhancing muscle performance or recovery from fatigue
wherein said method comprises administering a composition
comprising a ketoacid and an amino acid wherein said amino acid is
cationic or dibasic.
The prior art ad describes a supplement containing the recited
components to increase muscle strength, size and mass and to help
muscles recuperate faster after exercise;
The ad also describes how the product is made and instructs a user on
the amount to take.
Anticipation
Iovate argued that the ad failed:
to disclose an effective method of “enhancing muscle performance or
recovery from fatigue;” and
2. to teach an “effective amount” of the components;
1.
The court rejected these contentions, holding:
1.
The ad’s disclosure of increasing muscle strength and helping
muscles recuperate faster after exercise anticipates “enhancing
muscle performance” and “recovery from fatigue;”
1.
The claims do not restrict the method to an “effective amount” and in
any event the prior art discloses such amount; and
Anticipation
Iovate also argued that the ad failed to enable the method because
the ad “lacks any guidance on appropriate ingredient dosages”
BSN responded that, “because the claims are not directed to any
particular concentrations, ratios, or percentages, one of skill in the
art could practice the invention by buying the individual ingredients”
or “the product itself.”
The Court agreed with BSN because “all one of ordinary skill in the
art would need to do to practice an embodiment of the invention is
to mix together the known ingredients listed in the ad and
administer the composition as taught by ad.”
Obviousness
In re Kubin, (Fed. Cir 2009):
In view of KSR, Federal Circuit finds that a
prior art protein, even of unknown
structure, renders obvious the cDNA
encoding it.
Obviousness
Kubin claimed:
An isolated nucleic acid molecule comprising a polynucleotide
encoding a polypeptide at least 80% identical to amino acids 22221 of SEQ ID NO:2, wherein the polypeptide binds CD48.
The prior art disclosed:
1.
The protein called “NAIL” encoded by the nucleic acid;
2.
Antibodies specific to the protein; and
3.
Cloning techniques for obtaining the polynucleotide.
Obviousness
On appeal Kubin argued that the prior art did not enable its NAIL
DNA; noting that its isolation method was different from the
isolation method of the prior art;

The court found this irrelevant absent a suggestion that the prior
art technique, even if different, would not yield the claimed
polynucleotide;

The court also found Kubin’s statement in the specification that
its claimed gene sequence can be derived and isolated by
“standard biochemical methods” discussed in a well-known
manual on cloning techniques belied its argument that isolation
of the DNA was not routine

But there may have been confusion between DNA isolation and
finding a suitable library.
Obviousness
Kubin also argued that the Board’s decision is inconsistent with In
re Deuel;

In Deuel, the Federal Circuit held that prior art teaching (1) a
method of gene cloning, and (2) a partial amino acid sequence
of a protein, did not render obvious DNA molecules encoding
the protein, because:
“[K]nowledge of a protein does not give one a
conception of a particular DNA encoding it.” It’s
merely obvious to try.
Obviousness
Federal Circuit holds that Deuel overruled by KSR!

“Insofar as Deuel implies the obviousness inquiry cannot
consider that the combination of the claim’s constituent
elements was ‘obvious to try,’ the Supreme Court in KSR
unambiguously discredited that holding.”
Obviousness
The court cited two situations where non-obviousness is found
in an obvious to try situation:
1.
to vary all parameters or try each of numerous possible choices
until one possibly arrived at a successful result, where the prior
art gave either no indication of which parameters were critical or
no direction as to which of many possible choices is likely to be
successful; or
2.
to explore a new technology or general approach that seemed
to be a promising field of experimentation, where the prior art
gave only general guidance as to the particular form of the
claimed invention or how to achieve it.
Obviousness
In Altana Pharma AG v. Teva, (Fed. Cir. 2009), the Federal Circuit affirmed
the district court’s refusal to grant a preliminary injunction because Altana
was not likely to prevail on the merits as to validity.
The claim recited a compound of formula:
The prior art ‘518 patent disclosed “compound 12” (out of 18 disclosed
compounds) having a methyl group, -CH3 at position R3 whereas the
claimed preferred compound included a methoxy group, -OCH3 at position
R3
Obviousness
Altana argued error in the selection of “compound 12” as a “lead
compound” because the prior art suggested numerous other
compounds at least as promising to modify as compound 12.

The court held that the prior art need not point to a single lead
compound for further development efforts, and that Altana’s restrictive
view of the lead compound test would present a rigid test similar to the
TSM test that the Supreme Court rejected in KSR;

Here compound 12 was properly selcted as a lead compound
because (1) the prior art taught that it was an improvement over the
prior art; (2) was one of the more potent of the eighteen compounds
and; (3) was relied on by the patent examiner during prosecution.
Obviousness
The court next addressed whether it was obvious to substitute the R3 methyl
group of prior art compound 12 with claimed methoxy group;

The district court determined that one of skill in the art would have
been motivated to modify the prior art compounds to reduce their
pKa to 4 because Sachs taught that a pKa of 4 would lead to better
stability of the compound within the body;

Bryson taught lowering pKa through substitution of a methoxy
group for a methyl group at 3-position of the pyridine ring;
The court held that “the defendants had made out a sufficient case of
obviousness to defer the matter for trial on the merits, as opposed to
granting the preliminary relief sought by the plaintiffs.”
Obviousness
In Bayer Schering Pharma AG v. Barr Laboratories (Fed. Cir. 2009), Bayer
claimed a pharmaceutical composition comprising (1) micronized
drospirenone particles in an oral dose form exposed to the gastric
environment upon dissolution, (2) an ethinylestradiol and (3) a carrier,
the composition being effective for oral contraception in a human female.

The prior art disclosed the use of drospirenone with the
ethyinylestradiol as an oral contraceptive.

Bayer distinguished the prior art because it micronized its composition
to increase its bioavailability.

Bayer argued that it was not obvious to prepare an exposed, i.e.
uncoated micronized composition, because it was believed at the time
of the invention that an enteric coating was necessary for protection
against the highly acidic gastric environment.
Obviousness
The court viewed the prior art as giving one of ordinary
skill in the art a choice between “two known options”:
1.
Delivery of micronized drospirenone by a normal pill following
the spirorenone analogy of “Krause” (a drug alleged to be
analogous to drospirenone which was absorbed before
adversely affected by acid); or
2.
Delivery of drospirenone by an enteric-coated pill following the
“Nickisch” in vitro teaching that the drug needs to be protected
from the stomach.
Obviousness
Citing KSR, the court concluded that these two options,
one pointing towards the invention and one pointing away,
constituted “a finite number of identified, predictable
solutions”:
“Because the selection of micronized drospirenone in a normal
pill led to the result anticipated by the Krause series, the
invention would have been obvious."
Obviousness
In Proctor & Gamble v. Teva Pharmaceuticals, (Fed. Cir. 2009),
P&G claimed the compound risedronate (3-pyr EHDP), which is
the active ingredient in the drug ACTONEL®;
 In the claimed risedronate (3-pyr EHDP), a hydroxy-ethanediphosphonate group is connected to the #3 carbon of a
pyridine ring;
 In the closest prior art compound (2-pyr EHDP), the hydroxyethane-diphosphonate group is connected to the #2 carbon of
the pyridine ring;
Teva argued that risedronate was obvious in view of the prior art
and that 2-pyr EHDP are positional isomers.
Obviousness
P&G’s expert testified that a person having ordinary skill in the art
realized that the properties of bisphosphonate compounds
(including the claimed 3-pyr EHDP and the prior art 2-pyr EHDP)
are members, could not be anticipated based on their structure.
P&G cited a noted authority on bisphosphonates confirming that
each bisphosphonate exhibits its own physical-chemical, biological
and therapeutic characteristics, so that each bisphosphonate has to
be considered on its own.
P&G confirmed this unpredictability by showing that another
structural isomer, 4-pyr EHDP, was not active in inhibiting bone
resorption despite its close relationship with the 2-pyr and 3-pyr
compounds, which are active.
Obviousness
The Federal Circuit agreed that the compound was non-obvious;
First, the court noted that to the extent an art is unpredictable, as
the chemical arts often are, solutions are less likely to be genuinely
predictable even post-KSR.
Here, there was no “reasonable expectation of success” because,
as noted in KSR, this was not a case when an obvious modification
“leads to the anticipated success,” thereby making the invention the
product of ordinary skill;
Is this case consistent with Bayer Schering Pharma in the sense
that here, as in Bayer, there was one modification that was
successful (2→3) and one that was not (3 →4)?
Enablement
In In re ‘318 Patent Litigation, the court reviewed the enablement of a
claim directed to a “method of treating Alzheimer’s disease and
related dementias which comprises administering to a patient
suffering from such a disease a therapeutically effective amount of
galanthamine or a pharmaceutically-acceptable acid addition salt
thereof.”
Enablement
The district court found that the specification did not demonstrate
utility because:
1.
Relevant animal testing experiments were “not finished . . . by the
time the ’318 patent was allowed”;
2.
The specification provided only “minimal disclosure” of utility; and
3.
The application “only surmise[d] how the claimed method could be
used” without providing sufficient galantamine dosage information.
Enablement
The Federal circuit affirmed.
The court acknowledged that “human trials are not required for a therapeutic
invention to be patentable.”
Rather, “results from animal tests or in vitro experiments may be sufficient to
satisfy the utility requirement.”
Here, however, patentee provided “neither in vitro test results nor animal test
results involving the use of galantamine to treat Alzheimer’s-like conditions.”
Instead, applicant relied on “connecting the dots” of knowledge 1) that
galanthamine was a safe cholinesterase inhibitor having selective nicotinic
effects but modest muscarinic receptor side effects; and 2) that nicotinic
receptors in the brain are involved with the ability to learn (unlike prior art
treatments, which had primarily affected muscarinic receptors).
Enablement
The court rejected patentee’s attempt to establish utility “by analytic reasoning,”
finding that:
1.
These “insights” “are nowhere described in the specification;
2.
There was no evidence that someone skilled in the art would infer
galantamine’s utility from the specification”; and
3.
The inventor herself testified that she “certainly wasn’t sure, and a lot of
other people weren’t sure that cholinesterase inhibitors [a category of
agents that includes galantamine] would ever work.”
The court concluded that “the specification, even read in the light of the
knowledge of those skilled in the art, does no more than state a hypothesis
and propose testing to determine the accuracy of that hypothesis.”
Product-by-Process
In Abbott Laboratories v. Sandoz, Inc. (Fed. Cir. 2009), an en banc
panel of the Federal Circuit holds that product-by-process claims are
limited to the recited process steps for infringement purposes.
An exemplary claim recited:
Crystalline 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]3-vinyl-3-cephem-4-carboxylic acid (syn isomer) which is obtainable
by acidifying a solution containing 7-[2-(2-aminothiazol-4-yl)-2hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylic acid (syn
isomer) at room temperature or under warming.
Product-by-Process
Prior to Abbott, there was a split of authority among two Federal
Circuit panel decisions regarding analysis of product-by-process
claims in infringement analyses:

Atlantic Thermoplastics held that process terms in product-byprocess claims serve as limitations in determining infringement;

Alternatively, Scripps held that product-by-process claims are not
limited to product prepared by the process set forth in the claims.
Product-by-Process
The Federal Circuit endorsed Atlantic Thermoplastics:

“[B]ased on Supreme Court precedent and the treatment of
product-by-process claims throughout the years by the PTO and
other binding court decisions, this court now restates that ‘process
terms in product-by-process claims serve as limitations in
determining infringement.’ … As noted earlier, this holding follows
this court’s clear statement in In re Thorpe that ‘product by
process claims are limited by and defined by the process.”
Product-by-Process
The court also rejected Abbott’s argument that use of the language
“obtainable” in the claim meant that the product did not actually
have to be “obtained by” the claimed process:

Patentee’s use of “obtainable” rather than “obtained by” cannot give it a
free pass to escape ambit of the product-by-process claiming doctrine.
Claims that include such ambiguous language should be viewed
extremely narrowly.

If this court does not require, as a precondition for infringement, that an
accused infringer actually use a recited process, simply because of the
patentee’s choice of the probabilistic suffix “able,” the very recitation of
that process becomes redundant.
Double patenting
In Takeda Pharm. v. Doll, (Fed. Cir. 2009), applicant claimed:
A process for preparing a cephem
compound of the formula:
A member selected from the group
consisting of (a) a cephem compound
of formula:
which comprises introducing an acyl
group of the formula:
into the amino group of the molecule of
formula:
(b) a pharmaceutically acceptable salt
thereof: or
(c) a pharmaceutically acceptable ester.
Double patenting
The parties argued, and the court accepted, an interesting
standard for obviousness of process claims in view of product
claims:

“Product and process claims are patentably distinct if multiple
processes for creating a product exist at the time of the invention.”
The court framed “[t]he novel legal question [as] whether laterdeveloped alternative processes are relevant in the productprocess ‘patentably distinct’ inquiry.”

PTO contends that the date of invention governs relevance of
products and processes in double patenting because other issues
relating to patentability are judged from the date of invention.

Applicant argues that PTO’s approach is too limited and that
processes developed after date of invention deserve a role in the
double patenting calculus.
Double patenting
The court was not persuaded by either approach “as neither
addresses the policies underlying the double patenting doctrine.”


The court concluded that it was the later process application that
actually triggers the potential of an “unjustified extension of patent
term.”
When filing the secondary application, the applicant essentially avers
that the product and process are “patentably distinct.”
Thus, the relevant timeframe for determining whether a product
and process are “patentably distinct” should be at the filing date
of the second application.

This rule gives the applicant the benefit of future developments in the
art while at the same time preventing the inequitable situation that
arises when an applicant attempts to rely on developments occurring
decades after the filing date of the secondary application.
Double patenting
In Amgen v. Hoffman-LaRoche (Fed. Cir. 2009), Amgen asserted
its patents covering EPO and Roche counterclaimed for
invalidity based on obviousness-double patenting:

The district court held that the claims of Amgen’s later patents were the
subject of a restriction requirement and therefore exempt from a double
patenting under the safe harbor of § 121;

On appeal, Roche argued that § 121 cannot shield the patents because
they issued from “continuation” applications to which § 121 is
inapplicable and not from “divisional” applications (to which the double
patenting protection of § 121 applies exclusively);
Double patenting

Federal Circuit reversed the district court on the double patenting
issue: “We conclude that because the … applications were filed
as continuation — rather than divisional — applications, the …
patents do not receive the benefit of § 121.”

Court referred to its earlier holding in Pfizer v. Teva that the safe
harbor applies only to divisionals, and not to divisional CIPs.

“Because the ’178 and ’179 applications were filed as continuation
applications instead of divisional applications, we hold that the
’933, ’422, and ’349 patents do not receive the protections
afforded by § 121’s safe harbor.”
Double patenting
Is Amgen’s holding consistent with previous Federal Circuit treatment
of “continuations” or “CIPs” filed as a result of restriction requirement?
The answer is NO.
See, e.g., Applied Materials Inc. v. Advanced Semiconductor
Materials, (Fed. Cir. 1996) where Applied Material’s patent 4,496,609
was filed as a CIP after subject to a restriction requirement, yet the
protection of 121 not only applied, but was not even an issue.
Double patenting
Roche next contended that Takeda changed the time frame for an
obviousness-type double patenting analysis.

Roche honed in on the language in the Takeda opinion stating that “the
relevant time frame for determining whether a product and process are
‘patentably distinct’ should be at the filing date of the secondary
application”;

Amgen argued that Takeda only allows the patentee an opportunity to
rely on post-invention evidence;

The Court sided with Amgen: “Roche’s view that Takeda changed the
time frame of the obviousness-type double patenting inquiry in all cases
collides with 35 U.S.C. § 120,” which provides that a qualifying
“application for patent for an invention . . . shall have the same effect . . .
as though filed on the date of the prior application.”
Double patenting
Because of § 120, we read Takeda to stand for the limited
proposition that an applicant can only rely on subsequent
developments in the art up to the filing date of the “secondary
application” in order to show that alternative processes to make the
product render the product and the process for making that product
patentably distinct.
On remand, Takeda will permit Amgen, if it wishes to do so, to rely on
alternative processes for making the products claimed in the ’933 and
’422 patents up to their filing dates to prove that the claims of those
patents and the claims of the ’868 and ’698 patents are patentably
distinct.
Thank You!
Robert M. Schulman