Details for Patent: 5,508,297

Summary for Patent: 5,508,297

Title:	Vascular hypertrophy suppression treatment
Abstract:	This invention relates to a method for the prophylaxis or treatment of vascular hypertropy in a mammal by administering a pharmaceutically effective amount of a compound represented by the formula (I): wherein ring W is a nitrogen-containing heterocyclic ring residue which may be substituted; R1 is hydrogen or an optionally substituted hydrocarbon residue which optionally binds through a hetero-atom; R3 represents a group capable of forming an anion or a group capable of changing thereto; X shows that the phenylene and phenyl groups bind to each other directly or through a spacer having an atomic length of two or less; n denotes 1 or 2; a and b forming the heterocyclic ring residue are independently one or two optionally substituted carbon or hetero atoms; c is an optionally substituted carbon or hetero atom; provided that, when the ring W is a condensed ring, R1 is hydrogen or an optionally substituted hydrocarbon residue which binds through a hetero atom, or a salt thereof to a mammal in need thereof.
Inventor(s):	Kohei Nishikawa
Assignee:	Takeda Pharmaceutical Co Ltd
Application Number:	US08/201,122
Patent Claim Types: see list of patent claims	Use;

US Patent 5,508,297: Candesartan Cilexetil Vascular Hypertrophy Claims and Patent Landscape

US Patent 5,508,297 protects the use of candesartan cilexetil, including pharmaceutically acceptable salts, to prevent or treat vascular hypertrophy. The patent covers two specified post-procedure settings: restenotic or hypertrophic vascular disease following percutaneous transluminal coronary angioplasty and vascular hypertrophy following bypass surgery.

The patent is a method-of-use patent, not a composition-of-matter patent. Its claims do not broadly cover candesartan cilexetil for hypertension, manufacture of the compound, or every pharmaceutical formulation. The patent term has expired, eliminating current US enforcement risk under the issued claims.

What drug and active ingredient does US Patent 5,508,297 cover?

The compound named in claim 1 is candesartan cilexetil, identified chemically as:

"(±)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate"

Candesartan cilexetil is an orally administered prodrug converted in vivo to candesartan. Candesartan is an angiotensin II receptor blocker that selectively antagonizes the AT1 receptor. The product was commercialized in the United States as Atacand by AstraZeneca, under rights originating with Takeda Pharmaceutical.

Item	Detail
Patent	US 5,508,297
Patent type	Method of treatment
Active compound	Candesartan cilexetil
Therapeutic mechanism	AT1 angiotensin II receptor antagonism
Primary claimed use	Prevention or treatment of vascular hypertrophy
Specific procedures	Percutaneous transluminal coronary angioplasty and bypass surgery
Original patent owner	Takeda Chemical Industries, Ltd.
Issue date	April 16, 1996
Patent status	Expired
FDA product association	Atacand, candesartan cilexetil
Molecular category	Small molecule, not biologic

The patent’s compound definition is unusually specific. It does not claim a broad class of angiotensin receptor blockers or all benzimidazole derivatives. It identifies one racemic candesartan cilexetil compound and its pharmaceutically acceptable salts.

What are the claims of US Patent 5,508,297?

Claim 1: Broad vascular-hypertrophy method

Claim 1 requires four principal elements:

1. A mammalian patient.
2. Prevention or treatment of vascular hypertrophy.
3. Administration of a pharmaceutically effective amount.
4. Administration of candesartan cilexetil or a pharmaceutically acceptable salt.

The claim is not limited to one dosage, route of administration, treatment duration, formulation, or disease stage. It also does not expressly limit treatment to coronary arteries. The term "vascular hypertrophy" can encompass abnormal thickening or growth of vascular smooth-muscle tissue, subject to the ordinary meaning of the term and the patent’s specification.

The claim requires therapeutic administration. Mere possession, manufacture, sale, or formulation of candesartan cilexetil would not by itself practice claim 1. Infringement would generally require performance of the claimed treatment method or activity that induces such performance under the applicable provisions of 35 U.S.C. § 271.

Claim 2: Post-angioplasty vascular hypertrophy

Claim 2 depends on claim 1 and narrows the indication to vascular hypertrophy occurring after percutaneous transluminal coronary angioplasty, commonly abbreviated PTCA.

This claim targets the biological response that can follow balloon angioplasty, including neointimal proliferation and restenotic vessel-wall changes. It does not claim the angioplasty procedure itself. It claims administering candesartan cilexetil to prevent or treat the resulting vascular hypertrophy.

A product label that expressly instructs use after angioplasty would present the clearest historical infringement theory. A label limited to hypertension would not necessarily practice claim 2.

Claim 3: Post-bypass vascular hypertrophy

Claim 3 depends on claim 1 and applies when vascular hypertrophy occurs after bypass surgery.

The claim does not identify a particular bypass vessel, surgical technique, dosage, or treatment interval. It therefore reaches a broader range of bypass-surgery settings than claim 2, although the underlying requirement remains prevention or treatment of vascular hypertrophy.

How broad is the scope of claim 1?

Claim 1 has broad therapeutic wording but narrow compound coverage.

Limitations that expand scope

The claim is not restricted to:

• Hypertension;
• Coronary arteries;
• A particular vascular bed;
• Oral administration;
• A particular dose;
• A particular dosage form;
• A specific patient age;
• A defined treatment duration; or
• A specific post-operative interval.

The claim also covers pharmaceutically acceptable salts of the named compound. This language could reach salts involving the acidic tetrazole functionality, provided the salt remains the claimed therapeutic compound and is pharmaceutically acceptable.

Limitations that narrow scope

The claim does not cover:

• Losartan;
• Valsartan;
• Irbesartan;
• Telmisartan;
• Olmesartan;
• Generic benzimidazole AT1 antagonists;
• Candesartan without the cilexetil prodrug group;
• Unrelated anti-restenotic agents;
• Any use of candesartan cilexetil unrelated to vascular hypertrophy.

The "±" designation identifies the racemic form. The issued claim is directed to the specified racemate rather than a broad genus of stereochemical variants. Separate analysis would be required for an isolated enantiomer, although infringement could depend on claim construction, product composition, and the doctrine of equivalents.

What patents protect candesartan cilexetil?

The commercial patent estate for candesartan cilexetil historically included composition, therapeutic-use, formulation, and product-specific patents. The principal early US patents were distinct in scope.

Patent	General subject matter	Strategic role
US 5,196,444	Candesartan cilexetil and related benzimidazole compounds	Core compound protection
US 5,508,297	Prevention or treatment of vascular hypertrophy	Post-angioplasty and post-bypass method protection
Later formulation and product patents	Dosage forms, compositions, combinations, or manufacturing matters	Potential secondary protection

US 5,196,444 was the principal composition patent associated with candesartan cilexetil. US 5,508,297 added use protection for vascular hypertrophy. The two patents had different claim strategies:

• US 5,196,444 focused on the chemical entity.
• US 5,508,297 focused on a medical indication and patient setting.

The distinction mattered for generic entry. A generic company could challenge or wait for expiration of the composition patent while omitting a patented method from its label under the section viii "skinny label" mechanism, if the remaining label did not induce infringement of the method patent.

When did US Patent 5,508,297 lose exclusivity?

US Patent 5,508,297 issued before the 1995 change to the standard patent-term regime. Its term was governed by the transitional rules applicable to pre-June 8, 1995 applications. Public patent records associate the patent with an expiration date in December 2013, subject to any applicable term adjustment or extension recorded by the USPTO and FDA.

The patent is now expired. No enforceable patent exclusivity remains under claims 1 through 3.

Milestone	Date or period
Earliest development and priority period	Early 1990s
US filing period	December 1993
Patent issued	April 16, 1996
Core patent term endpoint	December 2013 period
Current status	Expired

The patent’s expiration is separate from FDA regulatory exclusivity. Patent expiration does not determine the original approval date, pediatric exclusivity, or the timing of ANDA approvals. Those events depended on the Orange Book listing, NDA history, regulatory exclusivity, and generic applicants’ certifications.

What was the Orange Book status of US Patent 5,508,297?

US 5,508,297 was historically associated with Atacand and candesartan cilexetil as a method-of-use patent. The FDA Orange Book distinguishes listed patents from active enforceable rights. A patent may remain historically listed in FDA records while its statutory term has expired.

The patent’s commercial importance was narrower than the core candesartan cilexetil patent because its claims focused on vascular hypertrophy after angioplasty or bypass surgery. Atacand’s principal approved indication was hypertension. Unless an approved label included the patented use, the patent would have had limited relevance to a generic applicant using a carved-out label.

The Orange Book analysis should therefore separate:

1. Whether the patent was historically listed;
2. Whether the patent remained unexpired at the relevant filing date;
3. Whether the proposed generic label included the patented method; and
4. Whether regulatory exclusivity independently delayed approval.

What Paragraph IV challenges affected candesartan cilexetil?

Candesartan cilexetil was subject to the standard Hatch-Waxman generic-entry process. An ANDA applicant seeking approval before expiration of an Orange Book-listed patent could file a Paragraph IV certification alleging that the patent was invalid, unenforceable, or not infringed.

For US 5,508,297, the principal legal issue would have been method-of-use infringement rather than chemical identity. A generic applicant could pursue one of two broad strategies:

Paragraph IV strategy

The applicant could challenge the patent by asserting that:

• The claims were invalid for anticipation or obviousness;
• The specification did not support the full scope of the claims;
• The claimed vascular-hypertrophy treatment lacked adequate written description or enablement;
• The proposed product label did not induce performance of the patented method; or
• The patent was otherwise unenforceable.

Section viii carve-out strategy

The applicant could omit the patented vascular-hypertrophy indication from its labeling if the remaining indications were not covered by the patent. This approach is particularly relevant where the patent claims a secondary indication that is distinct from the main commercial indication, such as hypertension.

A Paragraph IV certification historically could trigger a 30-month stay of FDA approval if the NDA holder or patent owner filed suit within the statutory period. That stay would affect regulatory approval timing, not the substantive patent term.

What litigation affected US Patent 5,508,297?

The patent was part of the broader US exclusivity and generic-entry framework for Atacand. The most commercially significant disputes involving candesartan cilexetil generally concerned the core compound patent and generic ANDA timing.

The available public record does not support treating US 5,508,297 as a currently active litigation barrier. Any historical infringement action would be legally moot as to future conduct after patent expiration, except for claims involving past damages within the applicable limitations period.

The principal litigation questions for this patent would have included:

• Whether an ANDA label encouraged post-angioplasty or post-bypass use;
• Whether a carved-out label removed the claimed use;
• Whether the claims were obvious in view of earlier AT1 antagonist research;
• Whether clinical evidence supported prevention or treatment of vascular hypertrophy; and
• Whether the patent term was correctly calculated.

How strong was the patent estate for candesartan cilexetil?

The estate was strongest for the chemical compound and weaker for the specific vascular-hypertrophy method.

Core compound protection

The composition patent generally provided the most valuable exclusionary right because it could cover the active pharmaceutical ingredient itself, regardless of the approved indication. A valid composition claim can block commercial manufacture and sale of the compound for multiple uses.

Method-of-use protection

US 5,508,297 had narrower commercial reach. It required proof of a patented use and could often be avoided by a label limited to noncovered indications. Its value depended on:

• Whether physicians used candesartan cilexetil after angioplasty or bypass surgery;
• Whether the FDA-approved label identified that use;
• Whether generic labels included or carved out the indication;
• Whether the claims survived validity challenges; and
• The remaining term of the core compound patent.

Formulation and manufacturing protection

Formulation patents can create additional barriers where they claim a specific dosage form, excipient system, particle size, process, or stability profile. They generally do not expand the scope of US 5,508,297, which contains no formulation limitation.

Manufacturing patents can affect process infringement and supply-chain strategy. They do not necessarily block a generic manufacturer using a noninfringing process, particularly where the active compound is no longer protected by a live composition patent.

Does US 5,508,297 create biosimilar risk?

No. Candesartan cilexetil is a chemically synthesized small molecule. It is subject to the ANDA generic pathway, not the biosimilar pathway under the Public Health Service Act.

Relevant competitive threats were:

• Generic candesartan cilexetil;
• Generic candesartan cilexetil/hydrochlorothiazide combinations;
• Authorized or licensed generic products;
• Alternative AT1 receptor blockers; and
• Combination products containing other antihypertensive agents.

Biosimilar interchangeability, biologic reference-product exclusivity, and the Biologics Price Competition and Innovation Act do not apply to this patent.

Which companies challenged or competed with Atacand?

The commercial competitive landscape included generic manufacturers pursuing candesartan cilexetil ANDAs and branded manufacturers selling competing AT1 receptor blockers. Relevant competitor products included:

• Losartan, marketed as Cozaar;
• Valsartan, marketed as Diovan;
• Irbesartan, marketed as Avapro;
• Telmisartan, marketed as Micardis; and
• Olmesartan, marketed as Benicar.

Generic companies that participated in the candesartan cilexetil market included major ANDA manufacturers such as Teva, Mylan, Sandoz, and others, depending on product strength, formulation, and approval period. Competition was driven principally by expiration of the core compound protection and the ability to obtain approval with a compliant label.

What generic launch scenarios existed?

Three scenarios were commercially relevant:

Scenario	Patent and label position	Likely result
Full-label generic after core patent expiry	Generic includes hypertension indication and other unprotected uses	Broad market entry
Skinny-label generic	Generic omits vascular-hypertrophy indication	Entry without practicing the carved-out method
Pre-expiration Paragraph IV launch	Generic challenges listed patent and wins, settles, or launches at risk	Earlier entry with litigation exposure

Because US 5,508,297 is expired, the third scenario no longer creates forward-looking risk under this patent. A current generic applicant’s principal analysis would instead focus on any later, unexpired patents, regulatory exclusivity, labeling obligations, and product-specific formulation rights.

What is the geographic coverage of US Patent 5,508,297?

The patent is a US national patent. Its claims apply only to conduct within the United States or conduct that falls within the territorial provisions of US patent law, including certain statutory rules governing components or products made abroad.

Corresponding foreign patent rights would require separate analysis. Patent rights in Europe, Japan, Canada, and other jurisdictions are independent and may have different:

• Filing dates;
• Priority claims;
• Claim scope;
• Patent-term calculations;
• Supplementary protection certificates;
• Opposition histories; and
• Expiration dates.

A US expiration does not establish worldwide freedom to operate.

Key Takeaways

• US 5,508,297 is a method-of-use patent covering candesartan cilexetil for prevention or treatment of vascular hypertrophy.
• Claim 1 covers the named racemic compound or a pharmaceutically acceptable salt in a mammal.
• Claim 2 is limited to vascular hypertrophy after percutaneous transluminal coronary angioplasty.
• Claim 3 is limited to vascular hypertrophy after bypass surgery.
• The patent does not broadly cover candesartan cilexetil, its manufacture, or all hypertension treatment.
• The patent was narrower than the core candesartan cilexetil composition patent, US 5,196,444.
• Its commercial relevance depended heavily on label content and the ability to omit the claimed indication.
• The patent expired in the December 2013 period and does not create current US exclusionary rights.
• Candesartan cilexetil is a small molecule subject to ANDA litigation, not biosimilar litigation.
• Current generic risk depends on later patents, formulation rights, regulatory exclusivity, and labeling, not US 5,508,297.

FAQs About US Patent 5,508,297

Does US 5,508,297 cover Atacand for hypertension?

No. The patent claims vascular-hypertrophy treatment and prevention. It does not expressly claim the general treatment of hypertension.

Does the patent cover candesartan cilexetil tablets?

Not as a product claim. The patent does not recite a tablet, capsule, excipient, release profile, or dosage form. It covers administration of the compound for the claimed vascular-hypertrophy use.

Could a generic company omit the claimed use from its label?

Historically, yes, if the omitted use could be carved out under the section viii pathway and the remaining label did not encourage infringement of claims 1 through 3.

Is US 5,508,297 still enforceable against a generic manufacturer?

No. The patent has expired. It cannot create prospective exclusionary rights against current generic manufacture, sale, or labeling.

Is candesartan cilexetil protected by a biologic exclusivity period?

No. Candesartan cilexetil is a small-molecule drug approved through the NDA pathway. Its generic competitors use ANDAs rather than biosimilar applications.

References

1. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services. https://www.fda.gov/drugsatfda

2. Food and Drug Administration. (1998). Atacand (candesartan cilexetil) prescribing information. U.S. Department of Health and Human Services.

3. United States Patent and Trademark Office. (1996). U.S. Patent No. 5,508,297: Treatment or prevention of vascular hypertrophy. https://patents.google.com/patent/US5508297

4. United States Patent and Trademark Office. (1993). U.S. Patent No. 5,196,444: Benzimidazole derivatives, processes for their preparation, and pharmaceutical compositions containing them. https://patents.google.com/patent/US5196444

5. 35 U.S.C. §§ 271, 282, 355. (2025). United States Code. Legal Information Institute, Cornell Law School. https://www.law.cornell.edu/uscode/text/35

6. 21 C.F.R. § 314.94. (2025). Content and format of an abbreviated new drug application. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-314.94

Drugs Protected by US Patent 5,508,297

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: 5,508,297

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	5-036630	Feb 25, 1993

International Family Members for US Patent 5,508,297

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	218861
Canada	2115985
Germany	69430766
European Patent Office	0612523
Spain	2173895
Japan	H06305966