RECENT FEDERAL CIRCUIT CASES CONCERNING

PHARMACEUTICAL ANDBIOTECH 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 pre-determined 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 IGFBP-5”); 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:

1. to disclose an effective method of “enhancing muscle performance or recovery from fatigue;” and

2. to teach an “effective amount” of the components;

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 22-221 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-ethane-diphosphonate group is connected to the #3 carbon of a pyridine ring;

In the closest prior art compound (2-pyr EHDP), the hydroxy-ethane-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)-2-hydroxyiminoacetamido]-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-by-process 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

A process for preparing a cephem compound of the formula:

which comprises introducing an acyl group of the formula:

into the amino group of the molecule of formula:

A member selected from the group consisting of (a) a cephem compound of formula:

(b) a pharmaceutically acceptable salt thereof: or

(c) a pharmaceutically acceptable ester.

In Takeda Pharm. v. Doll, (Fed. Cir. 2009), applicant claimed:

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 later-developed alternative processes are relevant in the product-process ‘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