Details for Patent: 8,168,616

Which drugs does patent 8,168,616 protect, and when does it expire?

Patent 8,168,616 protects VALTURNA and is included in one NDA.

This patent has ninety-three patent family members in thirty-one countries.

Summary for Patent: 8,168,616

Title:	Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
Abstract:	The invention relates to a combination comprising the renin inhibitor of formula (I) or a pharmaceutically acceptable salt thereof.
Inventor(s):	William Hewitt, Daniel Lucius Vasella, Randy Lee Webb
Assignee:	Noden Pharma DAC
Application Number:	US10/416,039
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

US Patent 8,168,616: Scope, Claims, Expiration, and Patent Landscape for Aliskiren-Valsartan

US Patent 8,168,616 protects pharmaceutical compositions combining aliskiren hemi-fumarate, a renin inhibitor, with valsartan or a pharmaceutically acceptable salt. The patent also covers use of that combination for hypertension and simultaneous, separate, or sequential administration. It was assigned to Novartis AG and was relevant to the Valturna fixed-dose combination, although the patent is now expired based on its published statutory term.

What drug combination does US Patent 8,168,616 protect?

The patent covers aliskiren, identified in the patent as the renin inhibitor of formula (I), combined with valsartan.

Element	Protected subject matter
Renin inhibitor	Aliskiren as the hemi-fumarate salt
Angiotensin receptor blocker	Valsartan or a pharmaceutically acceptable salt
Dosage-form requirement	A pharmaceutical composition with a carrier
Therapeutic use	Treatment of hypertension
Administration	Simultaneous, separate, or sequential use
Relevant product	Valturna, aliskiren/valsartan
Patent owner	Novartis AG
US patent	US 8,168,616 B2
Issue date	May 1, 2012
Patent status	Expired based on the published 20-year term

The claim is directed to a specific pharmacological combination. It does not cover every renin inhibitor combined with every angiotensin receptor blocker. The claimed renin inhibitor is limited to the patented formula, supplied as the hemi-fumarate, and the second active ingredient is limited to valsartan or its pharmaceutically acceptable salts. [1]

What are the claims of US 8,168,616?

Claim 1: Combination pharmaceutical composition

Claim 1 covers:

A pharmaceutical composition comprising the renin inhibitor of formula (I) as a hemi-fumarate, valsartan or a pharmaceutically acceptable salt thereof, and a carrier.

The principal limitations are:

1. The composition must contain the specified renin inhibitor.
2. The renin inhibitor must be present as the hemi-fumarate salt.
3. The composition must contain valsartan or a pharmaceutically acceptable salt.
4. The composition must include a carrier.

The claim is broad as to the carrier and formulation architecture. A carrier could include conventional excipients used in tablets, capsules, powders, solutions, suspensions, or other pharmaceutical dosage forms. The claim does not, on its face, require a particular dose ratio, release profile, tablet strength, particle size, coating, or manufacturing process.

The claim is narrower than a generic claim to "a renin inhibitor plus an angiotensin receptor blocker." It does not expressly cover aliskiren combined with losartan, irbesartan, candesartan, telmisartan, or another ARB.

Claim 2: Hypertension use

Claim 2 covers the composition of claim 1 for treatment of hypertension.

This claim adds a therapeutic-use limitation. It does not create a separate product composition independent of claim 1. A product must still satisfy the aliskiren-hemi-fumarate, valsartan, and carrier limitations.

The claim is relevant to products labeled for hypertension, including fixed-dose combinations and co-packaged or separately administered products used for that indication.

Claim 3: Simultaneous, separate, or sequential administration

Claim 3 covers the composition of claim 1 for simultaneous, separate, or sequential use.

This language is significant because it reaches beyond a single tablet containing both active ingredients. It may encompass:

• A single fixed-dose unit containing aliskiren and valsartan.
• Two separate dosage forms supplied for combined therapy.
• Administration of the two agents at the same time.
• Administration of one agent before the other.
• A regimen in which the products are administered sequentially.

The claim remains dependent on claim 1. The separate or sequential-use language does not eliminate the requirement that the claimed therapeutic arrangement involve the specified aliskiren hemi-fumarate and valsartan combination.

How broad is the claim scope?

US 8,168,616 has meaningful combination-therapy scope but limited molecular scope.

Potential product or regimen	Likely relevance to claim 1
Aliskiren hemi-fumarate plus valsartan	Within the core claim scope
Valturna fixed-dose tablet	Directly aligned with the claimed subject matter
Aliskiren hemi-fumarate and valsartan in separate tablets	Potentially covered through claim 3
Aliskiren plus valsartan administered sequentially	Potentially covered through claim 3
Aliskiren plus losartan	Outside the literal valsartan limitation
Valsartan plus hydrochlorothiazide	Outside the renin-inhibitor limitation
A different aliskiren salt	Potentially outside claim 1 if not the claimed hemi-fumarate
Aliskiren hemi-fumarate alone	Outside the combination requirement
Valsartan alone	Outside the combination requirement
A composition without a pharmaceutical carrier	Potentially outside claim 1

The strongest infringement theory would involve a product containing both aliskiren hemi-fumarate and valsartan. A separate-tablet regimen would require a closer analysis of product configuration, labeling, intended use, and whether the accused arrangement satisfies the claim language.

What product was associated with the patent?

The principal commercial product associated with the patent was Valturna, a fixed-dose combination of aliskiren and valsartan developed by Novartis.

Valturna was approved by the FDA for hypertension. The product combined:

• Aliskiren, a direct renin inhibitor.
• Valsartan, an angiotensin II receptor blocker.

The FDA later required significant labeling changes for aliskiren-containing products after safety concerns involving combined renin-angiotensin system blockade. The ALTITUDE study evaluated aliskiren in high-risk patients with type 2 diabetes and renal disease receiving background renin-angiotensin system therapy. The study was stopped early, and FDA communications warned against combining aliskiren with an ACE inhibitor or ARB in patients with diabetes because of risks including renal impairment, hypotension, and hyperkalemia. [2]

Novartis announced that Valturna would be withdrawn from the US market in response to the regulatory safety concerns. The commercial withdrawal reduced the practical value of the combination patent even before expiration.

When did US Patent 8,168,616 expire?

The patent’s published priority and term information point to a statutory expiration in 2022, subject to any applicable patent-term adjustment, terminal disclaimer, or other term modification recorded in the official patent file.

Milestone	Date or status
US patent	8,168,616
Grant	May 1, 2012
Patent term basis	Generally 20 years from the earliest effective nonprovisional priority filing
Published expiration	2022
Current enforcement position	No ordinary infringement action can be based on an expired patent

The expiration date should be checked against the USPTO Patent Center record and the Orange Book patent listing because a patent’s effective expiration can differ from a simple 20-year calculation where PTA, PTE, terminal disclaimers, or corrected records apply. [3]

Because the patent has expired, it no longer creates a current US patent barrier to an ANDA applicant or other developer. Historical infringement exposure remains relevant for conduct before expiration, but future commercial entry is not blocked by this patent.

What was the Orange Book status of Valturna and US 8,168,616?

Valturna was an FDA-approved prescription product, and Novartis was the relevant innovator sponsor. The FDA Orange Book is the authoritative source for listed patents, exclusivity periods, therapeutic equivalence information, and current product marketing status. [4]

US 8,168,616 was associated with the aliskiren/valsartan combination patent estate and was relevant to the product’s exclusivity analysis. The regulatory value of the listing was limited by three factors:

1. Valturna was withdrawn from the US market.
2. The patent term ended in 2022.
3. No biologic exclusivity or biosimilar pathway applied because aliskiren and valsartan are small-molecule drugs.

A withdrawn product can still have regulatory and litigation relevance. An ANDA applicant may need to address listed patents even if the reference product is no longer actively marketed, depending on the FDA’s product and patent records. The commercial value of that challenge, however, is materially lower when the reference product has been withdrawn and the listed patent has expired.

Were there Paragraph IV challenges to US 8,168,616?

No widely documented, commercially significant Paragraph IV litigation directed specifically at US 8,168,616 is established in the core public records associated with the patent.

This is consistent with the product history. Valturna was withdrawn, and the patent expired in 2022. Generic applicants had limited economic incentive to litigate a combination product that was no longer actively marketed by the reference sponsor.

A Paragraph IV certification against this patent would have required an ANDA applicant to assert that the patent was invalid, unenforceable, or not infringed. The principal potential defenses would have included:

• Lack of novelty based on earlier combination disclosures.
• Obviousness based on combining aliskiren and valsartan for hypertension.
• Lack of written description or enablement for the full scope of the composition or administration claims.
• Noninfringement based on a different salt, formulation, or administration arrangement.
• Patent-term or listing defects.

The strongest invalidity question would have concerned whether the claimed combination was obvious in view of prior renin-angiotensin system therapies and known combination-treatment strategies. Commercial success would have been a weak secondary consideration after Valturna’s withdrawal.

How strong was the patent estate?

The estate was strongest against a product that directly copied the Valturna concept: aliskiren hemi-fumarate plus valsartan in one dosage form or in a coordinated regimen.

Strengths

• The active ingredients are identified with reasonable specificity.
• The claim reaches both fixed-dose and, through claim 3, separate or sequential use.
• The composition claim is not limited to a narrow excipient system.
• Valsartan was a commercially established ARB with a defined chemical identity.
• The patent supported protection for the central aliskiren/valsartan combination rather than only a particular tablet design.

Weaknesses

• The claims do not cover other ARBs.
• The claims do not clearly require a distinctive formulation technology.
• The combination was vulnerable to obviousness arguments based on known blood-pressure treatment combinations.
• The product faced regulatory safety issues involving dual renin-angiotensin system blockade.
• The patent has expired.
• The commercial product was withdrawn before the end of the patent term.

The estate therefore had moderate historical blocking value but limited residual commercial value.

What formulation patents protect aliskiren or valsartan products?

US 8,168,616 is not primarily a formulation-technology patent. It requires a carrier, but it does not claim a defined dissolution profile, coating system, particle engineering method, dosage ratio, or manufacturing sequence.

Other patents in the broader aliskiren and valsartan landscape may cover:

• Aliskiren active pharmaceutical ingredient chemistry.
• Salt forms and crystalline forms.
• Tablet formulations.
• Manufacturing processes.
• Combination products involving hydrochlorothiazide or amlodipine.
• Methods of treating hypertension or cardiovascular disease.
• Specific dosing regimens.

Those patents must be analyzed separately. A product could avoid US 8,168,616 while still implicating another patent directed to aliskiren chemistry, valsartan formulation, or a different combination.

What manufacturing and IP barriers existed?

The patent did not impose a major manufacturing barrier by itself. A manufacturer would need to produce or source:

• Aliskiren in the claimed hemi-fumarate form.
• Valsartan meeting pharmaceutical quality requirements.
• A suitable carrier system.
• A dosage form meeting FDA quality, stability, dissolution, and bioequivalence standards.

The more substantial barriers were regulatory and commercial:

• Demonstrating bioequivalence for a fixed-dose combination.
• Addressing the historical FDA safety concerns surrounding aliskiren with ARB therapy.
• Establishing a commercially viable indication after Valturna’s withdrawal.
• Managing separate-tablet labeling and coordinated-use claims.
• Confirming freedom to operate under other aliskiren and valsartan patents.

How does US 8,168,616 compare with competing combination patents?

Patent category	Typical protected subject matter	Difference from US 8,168,616
Aliskiren compound patents	Chemical compound, salt, synthesis	Protect the active ingredient rather than the valsartan combination
Aliskiren-hydrochlorothiazide patents	Renin inhibitor plus diuretic	Different second active ingredient
Aliskiren-amlodipine patents	Renin inhibitor plus calcium-channel blocker	Different cardiovascular combination
Valsartan-hydrochlorothiazide patents	ARB plus diuretic	Does not require aliskiren
Valsartan-amlodipine patents	ARB plus calcium-channel blocker	Does not require aliskiren
US 8,168,616	Aliskiren hemi-fumarate plus valsartan	Specifically targets the Valturna combination

There is no biosimilar risk because the products are small-molecule drugs. The relevant competitive threats were generic products, alternative antihypertensive combinations, and substitution with other ARB-based therapies.

What licensing deals affected the patent landscape?

Aliskiren originated from research associated with Speedel Pharmaceuticals and was developed and commercialized by Novartis. Novartis acquired Speedel in 2008 after earlier collaboration and licensing arrangements involving aliskiren development. [5]

Those corporate transactions are relevant to ownership and commercialization history, but they do not expand the claim scope of US 8,168,616. The patent is evaluated based on its issued claims, recorded ownership, prosecution history, and term.

What generic launch scenarios existed?

The main US launch scenarios were:

1. Direct fixed-dose generic: A generic aliskiren/valsartan tablet could have directly implicated claim 1 before patent expiration.
2. Separate-tablet strategy: A manufacturer could have marketed separate aliskiren and valsartan products, but claim 3 created potential risk if the labeling promoted simultaneous or sequential combination use.
3. Alternative ARB strategy: A product combining aliskiren with an ARB other than valsartan would generally avoid the literal valsartan limitation.
4. Post-expiration entry: After expiration, the patent ceased to block US commercial entry, subject to other patents and FDA requirements.
5. Substitution strategy: Generic valsartan combinations with hydrochlorothiazide or amlodipine did not fall within the central claim because they lacked the specified renin inhibitor.

What is the current litigation and enforcement position?

US 8,168,616 is no longer an active patent barrier. Any present-day freedom-to-operate review should treat the patent as expired and focus on:

• Other active US patents covering aliskiren.
• Patents covering valsartan formulations or manufacturing.
• Orange Book records for any currently marketed reference products.
• FDA labeling restrictions for aliskiren and ARB combinations.
• Product-specific regulatory requirements for a new or generic combination.

No current US infringement action can be based prospectively on an expired patent. Historical litigation risk would require analysis of the accused conduct, product launch dates, damages period, prosecution history, and any settlement or covenant not to sue.

Key Takeaways

• US 8,168,616 covers aliskiren hemi-fumarate combined with valsartan or a pharmaceutically acceptable salt.
• Claim 1 is the core composition claim and requires a pharmaceutical carrier.
• Claim 2 limits the composition to hypertension treatment.
• Claim 3 reaches simultaneous, separate, and sequential administration.
• The patent was closely associated with Novartis’s Valturna product.
• Valturna was withdrawn after FDA safety concerns involving aliskiren and renin-angiotensin system blockade.
• The patent expired in 2022 based on its published statutory term.
• The patent did not cover aliskiren combinations with ARBs other than valsartan.
• No biosimilar pathway applies.
• Current generic risk from this patent is minimal because the patent is expired, although other aliskiren, valsartan, formulation, manufacturing, and regulatory barriers may remain.

FAQs

Does US 8,168,616 cover aliskiren alone?

No. The claims require aliskiren hemi-fumarate together with valsartan or a pharmaceutically acceptable salt.

Does the patent cover valsartan combined with hydrochlorothiazide?

No. Hydrochlorothiazide is not the claimed second active ingredient. The core claim specifically requires valsartan.

Can a manufacturer avoid claim 1 by using a different aliskiren salt?

Potentially. Claim 1 expressly identifies the renin inhibitor as the hemi-fumarate. A different salt could avoid literal infringement, although equivalence and other patent claims would require separate analysis.

Is Valturna still protected by US 8,168,616?

No. The patent expired, and Valturna was withdrawn from the US market.

Did US 8,168,616 create biosimilar competition risk?

No. Aliskiren and valsartan are small-molecule active ingredients regulated through the drug approval pathway, not biologics subject to biosimilar approval.

References

1. United States Patent and Trademark Office. (2012). US Patent No. 8,168,616 B2, Pharmaceutical composition comprising a renin inhibitor and valsartan.
2. U.S. Food and Drug Administration. (2012). FDA drug safety communication: New warnings and contraindications for blood pressure medicines containing aliskiren.
3. United States Patent and Trademark Office. (n.d.). Patent Center: US Patent No. 8,168,616.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
5. Novartis AG. (2008). Novartis completes acquisition of Speedel Pharmaceuticals.

Drugs Protected by US Patent 8,168,616

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	VALTURNA	aliskiren hemifumarate; valsartan	TABLET;ORAL	022217-001	Sep 16, 2009		DISCN	No	No	8,168,616		Y
Novartis	VALTURNA	aliskiren hemifumarate; valsartan	TABLET;ORAL	022217-002	Sep 16, 2009		DISCN	No	No	8,168,616		Y

Foreign Priority and PCT Information for Patent: 8,168,616

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0028151.9	Nov 17, 2000

PCT Information
PCT Filed	November 15, 2000	PCT Application Number:	PCT/EP01/13241
PCT Publication Date:	May 23, 2002	PCT Publication Number:	WO02/40007

International Family Members for US Patent 8,168,616

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1602370		91563	Luxembourg
European Patent Office	1602370		CA 2009 00010	Denmark
European Patent Office	1602370		C300385	Netherlands
European Patent Office	1602370		09C0020	France
European Patent Office	1602370		SPC/GB09/024	United Kingdom
European Patent Office	1602370		2009/010	Ireland