Litigation Details for Par Pharmaceutical, Inc. v. Twi Pharmaceuticals, Inc. (Fed. Cir. 2014)

« Back to Dashboard

Par Pharmaceutical, Inc. v. Twi Pharmaceuticals, Inc. (Fed. Cir. 2014)

Docket		Date Filed	2014-04-01
Court	Court of Appeals for the Federal Circuit	Date Terminated
Cause		Assigned To
Jury Demand		Referred To
Patents	6,375,986; 7,101,576
Link to Docket	External link to docket

Details for Par Pharmaceutical, Inc. v. Twi Pharmaceuticals, Inc. (Fed. Cir. 2014)

Date Filed	Document No.	Description	Snippet	Link To Document
2014-04-01				External link to document

Par Pharmaceutical, Inc. v. TWi Pharmaceuticals, Inc. Litigation Summary and Patent Analysis

Last updated: October 9, 2026

Par Pharmaceutical, Inc. v. TWi Pharmaceuticals, Inc., No. 14-1391, concerned TWi’s Paragraph IV challenge to Par’s patent covering the Megace ES formulation of megestrol acetate oral suspension. The U.S. Court of Appeals for the Federal Circuit reversed the district court’s obviousness ruling and held that the asserted claims were not invalid on the record presented. The decision preserved Par’s patent position against TWi’s ANDA product and confirmed that unexpected pharmacokinetic results can support nonobviousness when the prior art does not provide a reason to expect those results. [1]

What drug and formulation were at issue in Par v. TWi?

The litigation involved Megace ES, Par’s concentrated oral suspension containing megestrol acetate, an appetite stimulant used primarily for anorexia, cachexia, or significant weight loss in patients with AIDS.

Megace ES differs from conventional Megace oral suspension in its formulation and concentration. The product uses a nanoparticulate or micronized megestrol acetate formulation designed to improve oral absorption and reduce the effect of food on bioavailability. The commercial product is administered as a 625 mg/5 mL oral suspension, equivalent to 125 mg/mL of megestrol acetate. [2]

The patent dispute focused on formulation claims rather than the basic therapeutic use of megestrol acetate. The claimed technology addressed the relationship between:

• Megetrol acetate particle size;
• an aqueous oral suspension;
• surfactant content;
• enhanced absorption; and
• reduced food-effect variability.

The case was therefore a formulation patent dispute involving drug delivery and bioavailability, not a dispute over the chemical structure of megestrol acetate.

What patent protected Megace ES in the case?

The principal patent was U.S. Patent No. 6,593,318, assigned to Par Pharmaceutical. The Federal Circuit opinion treated the asserted claims of the ’318 patent as the relevant patent claims in the appeal. [1]

The patent covered pharmaceutical compositions containing megestrol acetate in a formulation intended to provide improved absorption. The claims were directed to the composition and related pharmaceutical characteristics rather than merely reciting megestrol acetate as an active ingredient.

Item	Detail
Patent	U.S. Patent No. 6,593,318
Patent holder	Par Pharmaceutical, Inc.
Active ingredient	Megestrol acetate
Dosage form	Oral suspension
Technology	Micronized or nanoparticulate formulation with surfactant and aqueous vehicle
Accused product	TWi’s proposed generic megestrol acetate oral suspension
Procedural posture	Hatch-Waxman patent litigation following an ANDA Paragraph IV certification
Federal Circuit case	No. 14-1391
Decision	Federal Circuit reversed the obviousness determination

The ’318 patent formed part of Par’s broader intellectual-property position around Megace ES. The case did not resolve every potential patent or regulatory issue affecting the product. It addressed the asserted claims and the obviousness analysis applied by the district court.

How did TWi challenge Par’s Megace ES patent?

TWi filed an abbreviated new drug application seeking FDA approval for a generic version of Megace ES. TWi made a Paragraph IV certification asserting that the ’318 patent was invalid, unenforceable, or would not be infringed by the proposed product.

Under the Hatch-Waxman framework, a Paragraph IV certification gives the patent holder a basis to sue for infringement before generic approval. Par filed suit against TWi, triggering the statutory 30-month stay of FDA approval under 21 U.S.C. § 355(j)(5)(B)(iii), subject to the statutory conditions and any court order affecting the stay. [3]

The litigation presented the standard ANDA question: whether the proposed generic product would infringe the asserted claims and, if so, whether those claims would survive TWi’s validity challenge.

TWi principally argued that the claimed formulation was obvious in view of prior-art megestrol acetate products, micronized megestrol acetate, and known pharmaceutical formulation techniques. The challenge relied on the proposition that a skilled formulator would have had reason to use smaller drug particles and a surfactant to improve dissolution and absorption.

What did the district court decide?

The district court held the asserted claims of the ’318 patent invalid as obvious. Its analysis treated the claimed formulation as an expected combination of known formulation elements.

The district court found that the prior art provided a motivation to formulate megestrol acetate using smaller particles and a surfactant. It also concluded that the skilled artisan would have had a reasonable expectation of success in obtaining improved absorption.

Par appealed the invalidity ruling to the Federal Circuit.

The district court’s approach reflected a common formulation-obviousness theory:

1. The active ingredient was already known.
2. Micronization was a recognized technique for improving dissolution.
3. Surfactants were known excipients.
4. The claimed composition combined known components for their expected functions.

The Federal Circuit rejected that analysis because it did not adequately account for the claimed formulation’s unexpected pharmacokinetic performance.

Why did the Federal Circuit reverse the obviousness ruling?

The Federal Circuit reversed because the prior art did not establish that a skilled artisan would have reasonably expected the claimed formulation to produce the relevant bioavailability results.

The court emphasized that obviousness requires more than identifying each claim element somewhere in the prior art. The challenger must show both:

• a reason to combine or modify the prior-art teachings; and
• a reasonable expectation that the modification would succeed.

The court found that TWi’s evidence did not satisfy that second requirement. The prior art suggested that particle-size reduction could affect dissolution, but it did not establish that the specific claimed formulation would produce the observed pharmacokinetic profile.

The Federal Circuit also credited evidence that the claimed formulation delivered unexpectedly improved absorption and reduced food-effect variability. Those results were relevant because the formulation had to operate in an oral delivery environment in which megestrol acetate’s absorption characteristics were not predictable solely from particle size.

The decision did not establish that every formulation using micronized megestrol acetate is nonobvious. Its holding was narrower: the evidence in this record did not prove that the specific claimed combination was an expected result of the prior art.

How important were unexpected results in the Federal Circuit’s analysis?

Unexpected results were central to the outcome.

Par relied on comparative data showing that the claimed formulation produced superior pharmacokinetic performance. The Federal Circuit treated the results as probative of nonobviousness because they were linked to the claimed formulation and were not predictable from the cited references.

The relevant considerations included:

• higher or improved bioavailability;
• reduced variability associated with food intake;
• the relationship between particle size and absorption;
• the role of surfactant in the formulation; and
• the absence of reliable prior-art guidance predicting the claimed result.

The court also rejected the idea that improved dissolution alone made the claimed pharmacokinetic performance predictable. Dissolution, absorption, systemic exposure, and food-effect behavior are related but distinct properties. A formulation that dissolves more readily does not necessarily produce the claimed in vivo result.

For formulation patents, the decision supports a practical litigation principle: comparative pharmacokinetic evidence is most valuable when it isolates the claimed feature and demonstrates a clinically or commercially relevant advantage over the closest prior art.

What was the final Federal Circuit outcome?

The Federal Circuit reversed the district court’s determination that the asserted claims were obvious. The court remanded the case for further proceedings consistent with its opinion. [1]

The ruling restored the validity of the asserted claims on the record before the court. It did not invalidate the patent, authorize TWi’s generic product, or establish that Par had waived its patent rights.

The key result was:

Issue	Federal Circuit result
Motivation to combine	Not sufficient by itself
Reasonable expectation of success	Not established
Unexpected pharmacokinetic results	Supported nonobviousness
’318 patent validity	Claims not shown obvious
TWi’s Paragraph IV position	Weakened
Generic launch based on the litigated challenge	Blocked unless otherwise permitted by patent expiry, settlement, or later proceedings

What was the Orange Book status of the Megace ES patent?

The litigation arose from an Orange Book-listed patent covering the Megace ES product. Under the Hatch-Waxman system, an ANDA applicant must address listed patents through certifications, including a Paragraph IV certification alleging invalidity or noninfringement. [3]

The case did not decide the broader Orange Book listing policy for all Megace ES patents. It addressed the patent claims placed in issue by TWi’s ANDA challenge.

The commercial effect of an Orange Book patent depends on several factors:

• whether the patent is listed against the reference product;
• whether the ANDA applicant makes a Paragraph IV certification;
• when the patent expires;
• whether pediatric exclusivity applies;
• whether a court enters an injunction;
• whether the parties settle; and
• whether other patents remain enforceable.

A favorable decision on one formulation patent does not automatically eliminate all generic-entry risk, but it can preserve a significant barrier when the patent covers the commercial product’s defining formulation.

Were there biosimilar issues in Par v. TWi?

No. Biosimilar law was not implicated.

Megestrol acetate is a small-molecule active pharmaceutical ingredient. TWi pursued an ANDA under the Hatch-Waxman Act, not a biologics license application under the Public Health Service Act or a biosimilar application under the Biologics Price Competition and Innovation Act.

The relevant regulatory pathway was:

Product type	Applicable pathway
Megace ES	New drug application
TWi generic	Abbreviated new drug application
Patent challenge	Paragraph IV certification
Biosimilar application	Not applicable

What generic-entry risks did TWi face?

TWi faced substantial entry risk after the Federal Circuit reversed the invalidity judgment.

The principal risks were:

Patent injunction or delayed approval

If the patent remained enforceable and the infringement case was resolved in Par’s favor, TWi could not commercially launch before the relevant patent barrier expired unless it obtained a license or reached a settlement permitting earlier entry.

Formulation substitution risk

A generic applicant could attempt to design around the asserted formulation claims. That strategy would require avoiding the claim limitations while maintaining comparable suspension stability, dose concentration, absorption, and manufacturability.

FDA approval risk

FDA approval of an ANDA does not eliminate patent risk. FDA approval and patent clearance are separate issues. A product may be approvable from a regulatory perspective while remaining subject to an injunction or damages exposure.

Commercial equivalence risk

A formulation that avoided the claims might not reproduce the reference product’s commercial properties. Differences in particle size, surfactant concentration, viscosity, redispersibility, or absorption could create regulatory and commercial complications.

How strong was Par’s patent estate after the decision?

The ’318 patent was strengthened against the specific obviousness theory litigated in the appeal. The Federal Circuit’s ruling established three practical advantages for Par:

1. The prior art did not make the claimed formulation predictable on the evidentiary record.
2. Pharmacokinetic data supported a nonobviousness position.
3. The patent covered formulation characteristics that were difficult to dismiss as routine excipient selection.

The estate’s strength was not unlimited. The decision did not eliminate risks based on:

• claim construction;
• infringement differences between the generic and branded formulations;
• written description or enablement;
• inequitable conduct;
• patent expiration;
• later-developed prior art; or
• alternative generic formulations.

The strongest commercial protection came from the combination of formulation limitations and demonstrated in vivo performance. A patent that claims only routine particle-size reduction would generally present a weaker barrier than a patent tied to a specific composition and unexpected pharmacokinetic result.

Did Par and TWi settle the litigation?

The Federal Circuit opinion resolved the appeal. The cited decision does not establish a settlement permitting an authorized TWi launch before patent expiry.

A Hatch-Waxman settlement would require separate analysis of the agreement’s entry date, payment terms, patent scope, and antitrust implications. No settlement terms should be inferred from the Federal Circuit’s reversal alone.

What was the business impact of the decision?

The ruling protected Par’s ability to maintain branded Megace ES exclusivity against the challenged TWi product. The commercial impact depended on the remaining life of the ’318 patent, the status of other Orange Book patents, the timing of FDA approval, and the availability of alternative generic formulations.

The decision also had broader value for pharmaceutical formulation litigation. It confirmed that a challenger cannot establish obviousness merely by showing that each individual formulation component was known. The challenger must connect the prior art to the claimed combination and show a reasonable expectation of the claimed performance.

For branded-drug companies, the decision supports investment in formulation patents supported by comparative pharmacokinetic data. For generic applicants, it raises the value of early formulation screening, design-around work, and testing directed at the precise claim limitations.

Key Takeaways

• Par v. TWi involved Megace ES, a megestrol acetate oral suspension.
• The principal patent was U.S. Patent No. 6,593,318.
• TWi challenged the patent through an ANDA Paragraph IV certification.
• The district court found the asserted claims obvious.
• The Federal Circuit reversed that ruling in No. 14-1391.
• The court held that TWi failed to prove a reasonable expectation of success.
• Unexpected bioavailability and reduced food-effect variability supported nonobviousness.
• The case involved Hatch-Waxman generic litigation, not biosimilar litigation.
• The ruling preserved Par’s patent position against the challenged TWi product.
• The decision remains relevant to formulation patents relying on particle size, surfactants, bioavailability, and pharmacokinetic evidence.

FAQs About Par Pharmaceutical v. TWi Pharmaceuticals

What was the Federal Circuit citation for Par v. TWi?

The decision is reported as Par Pharmaceutical, Inc. v. TWi Pharmaceuticals, Inc., 773 F.3d 1186 (Fed. Cir. 2014).

What was the active ingredient in the disputed product?

The active ingredient was megestrol acetate, marketed by Par as Megace ES oral suspension.

Did the Federal Circuit find the patent invalid?

No. The Federal Circuit reversed the district court’s ruling that the asserted claims were obvious.

Was TWi’s generic product approved by the FDA?

The litigation concerned TWi’s ANDA and Paragraph IV challenge. The Federal Circuit decision did not itself grant FDA approval or authorize commercial launch.

What patent-law principle came from the case?

The case confirms that obviousness requires a motivation to combine prior-art teachings and a reasonable expectation of success. Unexpected pharmacokinetic results can rebut an obviousness challenge when the prior art does not predict the claimed performance.

References

1. Par Pharmaceutical, Inc. v. TWi Pharmaceuticals, Inc., 773 F.3d 1186 (Fed. Cir. 2014).

2. U.S. Food and Drug Administration. (n.d.). Megace ES (megestrol acetate) oral suspension prescribing information. FDA.

3. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).