Details for Patent: 7,384,980

Summary for Patent: 7,384,980

Title:	Derivatives of 3,3-diphenylpropylamines
Abstract:	The invention concerns novel derivatives of 3,3-diphenylpropylamines, methods for their preparation, pharmaceutical compositions containing the novel compounds, and the use of the compounds for preparing drugs. More particularly, the invention relates to novel prodrugs of antimuscarinic agents with superior pharmacokinetic properties compared to existing drugs such as oxybutynin and tolterodine, methods for their preparation, pharmaceutical compositions containing them, a method of using said compounds and compositions for the treatment of urinary incontinence, gastrointestinal hyperactivity (irritable bowel syndrome) and other smooth muscle contractile conditions.
Inventor(s):	Claus Meese, Bengt Sparf
Assignee:	UCB Pharma GmbH
Application Number:	US11/201,756
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,384,980
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 7,384,980: Fesoterodine Scope, Claims, Expiration, and Patent Landscape

US Patent 7,384,980 covers the R-(+)-enantiomer of fesoterodine, its acid-addition salts, pharmaceutical compositions, and therapeutic use as a muscarinic receptor antagonist, including treatment of urinary incontinence. The patent issued June 10, 2008, and its ordinary U.S. patent term expired February 15, 2022. It is no longer an enforceable barrier to an ANDA applicant, although related formulation, salt, method-of-use, or manufacturing patents must be reviewed separately.[1][2]

What compound does US 7,384,980 protect?

The principal compound is fesoterodine, chemically identified in the patent as:

R-(+)-isobutyric acid 2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenyl ester.

Fesoterodine is a prodrug. In vivo, ester hydrolysis produces 5-hydroxymethyl tolterodine, commonly called 5-HMT. The active metabolite antagonizes muscarinic receptors and is responsible for the pharmacologic effect in overactive bladder and urinary incontinence.[3]

The marketed product is Toviaz, containing fesoterodine fumarate in extended-release tablets. The product was developed by Schwarz Pharma, later acquired by UCB, and commercialized in the United States by Pfizer under a commercialization arrangement.[3][4]

Item	Detail
Patent	US 7,384,980
Patent title	R-(+)-isobutyric acid 2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenyl ester
Active pharmaceutical ingredient	Fesoterodine
Marketed salt	Fesoterodine fumarate
Product	Toviaz extended-release tablets
Therapeutic area	Overactive bladder; urinary urgency, frequency, and urge urinary incontinence
Pharmacologic class	Muscarinic receptor antagonist
Patent issue date	June 10, 2008
Reported patent expiration	February 15, 2022
FDA pathway for competitors	ANDA
Biosimilar pathway	Not applicable

How broad are the claims of US 7,384,980?

The claims divide into four principal categories: the R-enantiomer, salts, compositions, and methods of treatment. Claims 8 through 16 broaden the patent to a group of related ester compounds and their racemic or enantiomeric forms.

Claims 1 and 2: R-fesoterodine and acid-addition salts

Claim 1 is a product claim directed to the R-(+)-enantiomer of fesoterodine. It does not claim the racemate. The stereochemical limitation is commercially important because the R-enantiomer is the form associated with the marketed active ingredient.

Claim 2 covers salts of the R-enantiomer with a physiologically acceptable acid. Fesoterodine fumarate falls within the ordinary scope of this type of salt claim because fumaric acid is a physiologically acceptable acid and the marketed product is the fumarate salt.

The claim structure therefore reaches both:

1. The free-base R-enantiomer; and
2. Acid-addition salts, including the fumarate salt used in Toviaz.

A generic product containing the same R-fesoterodine active moiety would not avoid the product claims merely by using a different pharmaceutically acceptable acid.

Claims 3 and 10: pharmaceutical compositions

Claim 3 covers a composition containing an effective amount of R-fesoterodine or a physiologically acceptable acid-addition salt, together with a pharmaceutically acceptable carrier.

Claim 10 covers compositions containing any member of the listed compound group in claim 8. The composition claims are broader than the marketed product in one respect because they are not limited on their face to an extended-release tablet, a particular excipient, a particular dissolution profile, or a particular dose.

The claims could therefore reach multiple dosage forms, including tablets, capsules, powders, and other conventional pharmaceutical compositions, provided the composition contains a claimed compound or salt.

They do not, however, expressly claim the specific Toviaz extended-release technology. A competitor may need to assess separate formulation patents if it uses the same release profile, excipient architecture, coating system, or manufacturing process.

Claims 4 and 5: muscarinic antagonism and treatment

Claim 4 is a method claim requiring administration of R-fesoterodine or a salt, resulting in contact between the muscarinic receptor and an effective amount of R-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenol, the active 5-HMT metabolite.

This claim links the prodrug administration step to the active metabolite's receptor interaction. Claim 5 covers treatment of a disease in a mammal that is amenable to treatment through muscarinic receptor antagonism.

These claims are not limited to urinary incontinence. Their language potentially encompasses a broader set of muscarinic-mediated disorders, subject to ordinary requirements for claim construction, enablement, written description, and proof of infringement.

Claims 6, 7, 15, and 16: urinary incontinence and human treatment

Claims 6 and 7 narrow the treatment method to urinary incontinence in a human patient. Claims 15 and 16 provide a parallel urinary-incontinence limitation for the broader compound group in claim 12.

These claims are the closest claims to the commercial indication for Toviaz. A generic applicant filing for fesoterodine fumarate extended-release tablets would typically address method-of-use patents through a Paragraph IV certification, a section viii statement, labeling restrictions, or a combination of those mechanisms, depending on the listed patent and the approved indication.

What compounds are covered by claims 8 through 16?

Claims 8 through 16 extend beyond the single R-fesoterodine compound. They cover a defined group of ester analogs sharing the 3-diisopropylamino-1-phenylpropyl phenyl core.

The listed compounds include:

Compound category	Ester substitution
Acetate derivative	Acetoxy and acetoxymethyl substitutions
n-Butyrate derivative	n-Butyric acid ester
Isobutyrate derivative	Isobutyric acid ester, including fesoterodine
Propionate derivative	Propionic acid ester
Diacylated derivatives	Additional isobutyryloxy or butyryloxy groups

Claim 8 expressly includes racemic mixtures and individual enantiomers, as well as physiologically acceptable salts. Claim 9 narrows the group to four hydroxy-methylphenyl ester derivatives:

• n-Butyric acid derivative;
• Isobutyric acid derivative;
• Propionic acid derivative; and
• Acetic acid derivative.

Claims 10 and 12 apply the composition and treatment limitations to the broader group. Claims 11 and 13 narrow those claims to the four compounds identified in claim 9.

The analytical significance is that claims 8 through 16 are genus and Markush-style claims. They potentially cover compounds other than fesoterodine, but their practical value depends on whether the listed alternatives are adequately supported by the specification and whether a marketed product falls within the precise structural language.

What is the scope of the urinary-incontinence claims?

The urinary-incontinence claims cover administering a claimed ester or salt in a pharmaceutical composition to a mammal, with claims 7 and 16 limiting the patient to a human.

The claims are not expressly limited to:

• A specific dose;
• Once-daily administration;
• Extended-release delivery;
• Fesoterodine fumarate specifically;
• A particular tablet strength;
• A particular patient subgroup; or
• A named diagnostic criterion.

That breadth would have made the claims relevant to a broad generic product targeting the approved urinary-incontinence indication during the patent term. Following expiration, the claims no longer create a current U.S. patent exclusion, but they remain relevant to historical Paragraph IV litigation and patent-term analysis.

When did US 7,384,980 lose exclusivity?

US 7,384,980 expired on February 15, 2022, based on the patent term reflected in FDA and patent records.[1][2]

Event	Date or status
Earliest relevant priority and filing history	Associated with the late-1990s fesoterodine development program
U.S. patent application	Filed before issuance of the patent
Patent issued	June 10, 2008
Reported expiration	February 15, 2022
Current enforceability	Expired
Current ANDA barrier from this patent	None
Pediatric exclusivity	Must be assessed separately from patent expiration and FDA exclusivity records

Patent expiration does not necessarily mark the end of all market protection for the product. A product may retain other patents, regulatory exclusivity, pediatric exclusivity, or commercial protection. For Toviaz, the central active-ingredient and enantiomer protection is no longer available as a current patent barrier.

What is the Orange Book status of fesoterodine?

Fesoterodine fumarate is an FDA-approved small-molecule drug listed in the Orange Book as an approved prescription product. Toviaz is approved as an extended-release tablet for symptoms of overactive bladder, including urge urinary incontinence, urgency, and frequency.[3]

The Orange Book analysis should distinguish among:

1. The active-ingredient patent represented by US 7,384,980;
2. Salt or polymorph patents;
3. Extended-release formulation patents;
4. Method-of-use patents; and
5. Any pediatric or regulatory exclusivity.

Because US 7,384,980 has expired, it no longer supports a valid Paragraph IV litigation strategy by itself. A current ANDA applicant's risk depends on whether an unexpired related patent remains listed against the relevant reference product and whether the proposed label overlaps the patented use.

FDA Orange Book records should be reviewed as of the relevant filing or launch date because listed patent status, delisting, and expiration information can change.[1]

Which companies challenged the Toviaz patent estate?

The Toviaz generic market has involved ANDA-based competition rather than biosimilar competition. Public records associate generic fesoterodine development with multiple generic manufacturers, including Teva and other ANDA sponsors.

The principal legal issues for an ANDA applicant would have included:

• Whether the proposed product contained R-fesoterodine;
• Whether the fumarate salt fell within the salt claims;
• Whether an extended-release tablet practiced separate formulation claims;
• Whether the proposed label induced infringement of urinary-incontinence method claims;
• Whether the patent was invalid for obviousness, lack of written description, anticipation, or indefiniteness; and
• Whether the applicant could use a section viii statement to omit a patented indication.

The expiration of US 7,384,980 materially changes the litigation posture. Any historical Paragraph IV action based solely on this patent no longer creates a prospective injunction against launch after expiration.

What Paragraph IV risks existed for fesoterodine generics?

During the patent term, an ANDA applicant seeking approval for a product containing fesoterodine fumarate could have certified under Paragraph IV that the patent was invalid, unenforceable, or would not be infringed.

A Paragraph IV notice involving US 7,384,980 could have triggered:

• A 45-day period for the patent owner or NDA holder to file suit;
• A potential 30-month FDA approval stay under the Hatch-Waxman Act;
• Discovery concerning stereochemistry, salt identity, prodrug conversion, and treatment claims;
• Invalidity challenges directed to the R-enantiomer and the broader compound genus; and
• Settlement negotiations involving launch dates, licenses, or covenants not to sue.

The practical risk was highest for a product using the same R-enantiomer and fumarate salt. A different ester analog might avoid claims 1 through 7 but could remain exposed to claims 8 through 16.

Are biosimilars relevant to US 7,384,980?

No. Fesoterodine is a chemically synthesized small molecule, not a biologic. Competitors use the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not the biosimilar pathway under the Public Health Service Act.

The relevant competitive issues are generic equivalence, salt identity, release characteristics, labeling, and patent certification. Biosimilar interchangeability, reference-product exclusivity, and biologic patent dance procedures do not apply.

What formulation patents protect Toviaz?

US 7,384,980 is not a detailed extended-release formulation patent. Its composition claims require a claimed active compound or salt and a pharmaceutically acceptable carrier, but they do not specify the commercial release system.

Toviaz's commercial presentation is an extended-release tablet. A complete freedom-to-operate review should therefore examine separate patent families covering:

• Extended-release fesoterodine tablets;
• Controlled dissolution and release rates;
• Tablet matrices or coatings;
• Fumarate salt forms;
• Particle size and solid-state properties;
• Manufacturing and granulation processes; and
• Stable pharmaceutical compositions.

Those families may have different expiration dates from US 7,384,980. They may also have been filed later and carry patent terms extending beyond the 2022 expiration date of the enantiomer patent.

How strong was the patent estate?

The estate was strongest against a product that copied all commercial attributes of Toviaz during the patent term:

• R-fesoterodine;
• A physiologically acceptable acid-addition salt;
• A urinary-incontinence indication;
• A pharmaceutical composition; and
• An extended-release dosage form covered by related patents.

US 7,384,980 had meaningful claim breadth because it combined a specific enantiomer claim with salt, composition, and method claims. Claims 8 through 16 provided additional chemical coverage but also created potential validity pressure because they covered a larger group of related compounds.

Risk factor	Assessment during patent term	Assessment after expiration
R-fesoterodine product claim	High	No current risk from this patent
Fesoterodine fumarate	High	No current risk from this patent
Generic extended-release tablet	Dependent on formulation patents	Dependent on unexpired related patents
Urinary-incontinence indication	High under method claims	No current risk from this patent
Alternative ester analog	Potentially covered by claims 8-16	No current risk from this patent
Salt substitution	May avoid a specific salt claim, but not broad salt language	No current risk from this patent
Biosimilar pathway	Not relevant	Not relevant

How does US 7,384,980 compare with the broader fesoterodine patent landscape?

US 7,384,980 is an enantiomer and therapeutic-use patent. It should not be treated as the entire Toviaz estate.

The broader landscape can be divided into five layers:

1. Core compound patents. These cover fesoterodine or related tertiary-amino phenyl esters.
2. Stereochemical patents. These focus on the R-enantiomer and may distinguish it from the racemate.
3. Salt and solid-state patents. These cover fumarate, crystalline forms, hydrates, solvates, or improved stability.
4. Formulation patents. These cover extended-release delivery and tablet composition.
5. Method-of-use patents. These cover overactive bladder, urinary urgency, frequency, and urge urinary incontinence.

The commercial product can be exposed to more than one layer at the same time. Expiration of the core enantiomer patent removes one barrier but does not automatically invalidate or expire other patents.

What generic launch scenarios exist for fesoterodine?

Launch after expiration of the core compound patent

This is the lowest-risk scenario if no related formulation or use patent remains enforceable. An ANDA applicant may market an equivalent fesoterodine fumarate extended-release product after FDA approval and completion of applicable exclusivity requirements.

Launch with a Paragraph IV challenge

Before expiration, an applicant could challenge listed patents by alleging invalidity, unenforceability, or noninfringement. A successful challenge could support an earlier launch. The risk would include a 30-month stay and district-court litigation.

Launch with a section viii statement

If a listed patent covered only a use that the generic applicant could omit from its labeling, the applicant could seek approval for unpatented indications. This strategy depends on the exact Orange Book listing and whether the remaining label still induces infringement.

At-risk launch

An applicant could launch before resolution of litigation if it accepted potential damages and injunction exposure. That scenario is commercially less relevant for US 7,384,980 because the patent has expired.

What licensing and settlement issues affect fesoterodine?

The relevant commercial rights have involved the originator, development partner, NDA holder, and generic manufacturers. Licensing and settlement agreements may have established:

• Authorized-generic rights;
• Royalty-bearing supply arrangements;
• Covenants not to sue;
• Agreed generic launch dates;
• Restrictions on dosage forms or indications; and
• Confidential commercial terms.

Settlement agreements in Hatch-Waxman cases are often not fully public. The enforceability and commercial significance of any particular agreement must be tied to the parties, patent numbers, launch date, and FDA approval status. US 7,384,980 itself does not create a current licensing requirement because it expired in 2022.

What geographic coverage does the patent have?

US 7,384,980 provides rights only in the United States. Equivalent protection may have existed in other jurisdictions through related national patent filings, but foreign expiration dates, claim scope, opposition outcomes, and supplementary protection certificates must be assessed country by country.

The U.S. expiration does not determine:

• European patent status;
• Canadian patent status;
• Japanese patent status;
• Australian patent status;
• Supplementary protection certificate periods;
• National patent-term adjustments; or
• Local regulatory exclusivity.

A global launch assessment therefore requires a separate family-level review.

Key Takeaways

• US 7,384,980 covers R-fesoterodine, including physiologically acceptable acid-addition salts such as fesoterodine fumarate.
• The patent also covers pharmaceutical compositions and treatment of muscarinic-mediated disease, with specific claims directed to urinary incontinence in humans.
• Claims 8 through 16 extend to related acetate, propionate, n-butyrate, and isobutyrate ester compounds, including racemates and individual enantiomers.
• The reported U.S. expiration date is February 15, 2022.
• The patent is expired and does not independently block current U.S. generic entry.
• Fesoterodine is a small molecule, so ANDA and Paragraph IV analysis applies; biosimilar law does not.
• Toviaz's extended-release formulation, salt, solid-state, manufacturing, and method-of-use patents must be reviewed separately.
• The principal current commercial issue is whether any related listed or unexpired patent remains relevant to a proposed generic label and dosage form.

FAQs

Is fesoterodine fumarate covered by US Patent 7,384,980?

Yes. Claim 2 covers salts of R-fesoterodine with physiologically acceptable acids, and fesoterodine fumarate is an acid-addition salt of the claimed R-enantiomer.

Can a generic manufacturer avoid the patent by using racemic fesoterodine?

During the patent term, a racemate could have raised a different infringement analysis for claims 1 through 7, but claims 8 through 16 expressly include racemic mixtures and individual enantiomers of listed compounds. The patent expired in 2022.

Does US 7,384,980 cover the Toviaz extended-release mechanism?

Not specifically. The patent claims compositions broadly but does not recite the detailed release technology of the marketed extended-release tablet. Separate formulation patents may have applied.

Is 5-HMT itself the compound claimed in US 7,384,980?

No. The patent primarily claims fesoterodine and related ester compounds. Claim 4 refers to receptor contact with 5-HMT after administration of fesoterodine or its salt.

Does expiration of US 7,384,980 permit immediate generic launch?

It removes this patent as a current barrier, but FDA approval, regulatory exclusivity, other Orange Book patents, formulation rights, and any settlement restrictions must still be assessed for the specific generic product.

References

1. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
2. United States Patent and Trademark Office. (2008). U.S. Patent No. 7,384,980: R-(+)-isobutyric acid 2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethylphenyl ester. https://patents.google.com/patent/US7384980
3. U.S. Food and Drug Administration. (2021). Toviaz (fesoterodine fumarate) extended-release tablets prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
4. Pfizer Inc. (n.d.). Toviaz prescribing information. https://labeling.pfizer.com/ShowLabeling.aspx?id=540

Drugs Protected by US Patent 7,384,980

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 7,384,980

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	98108608	May 12, 1998

International Family Members for US Patent 7,384,980

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1077912		CA 2007 00046	Denmark
European Patent Office	1077912		91365	Luxembourg
European Patent Office	1077912		07C0050	France
European Patent Office	1077912		SPC037/2007	Ireland
European Patent Office	1077912		SPC/GB07/053	United Kingdom
European Patent Office	1077912		SZ 47/2007	Austria