Details for Patent: 7,173,037

Which drugs does patent 7,173,037 protect, and when does it expire?

Patent 7,173,037 protects ADEMPAS and is included in one NDA.

This patent has forty-five patent family members in thirty-five countries.

Summary for Patent: 7,173,037

Title:	Carbamate-substituted pyrazolopyridines
Abstract:	The present invention relates to compounds which stimulate soluble guanylate cyclase, to the preparation thereof and to the use thereof as medicaments, in particular as medicaments for the treatment of cardiovascular disorders and/or sexual dysfunction.
Inventor(s):	Cristina Alonso-Alija, Erwin Bischoff, Klaus Münter, Johannes-Peter Stasch, Elke Stahl, Stefan Weigand, Achim Feurer
Assignee:	Adverio Pharma GmbH
Application Number:	US10/513,869
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,173,037
Patent Claim Types: see list of patent claims	Use; Composition; Process;

US Patent 7,173,037: Riociguat Claim Scope, Expiration, Orange Book Status and Patent Landscape

US Patent 7,173,037 is the foundational composition-of-matter patent for riociguat, marketed by Bayer as Adempas. Its claims cover the riociguat molecule, related N-substituted carbamate analogs, salts and hydrates, manufacturing processes, pharmaceutical compositions, combination therapy with nitric-oxide or cGMP-pathway agents, and treatment of hypertension and sexual dysfunction.

The patent issued on February 6, 2007, from a priority chain dating to 1999. Its ordinary US patent term expired in 2020. The patent therefore no longer blocks manufacture or sale of riociguat in the United States. Commercial risk now depends on later patents, regulatory exclusivity, formulation and method-of-use rights, and any litigation or settlement restrictions.

What drug does US Patent 7,173,037 protect?

The patent protects riociguat and a defined class of substituted pyrazolo[3,4-b]pyrimidine-related compounds.

Riociguat is the compound recited in claim 4:

Methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate.

Its accepted chemical name is methyl N-[4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]-N-methylcarbamate. Riociguat is a soluble guanylate cyclase stimulator used for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Item	Data
Patent	US 7,173,037 B2
Patent title	Pyrazolopyridine derivatives
Patent holder	Bayer AG
Issue date	February 6, 2007
Core product	Riociguat
US brand	Adempas
FDA approval	October 8, 2013
Primary FDA indications	Inoperable or persistent/recurrent CTEPH; PAH
Ordinary patent-term expiration	2020
Patent category	Composition of matter, process, composition, combination and treatment claims

The FDA approved Adempas for adults with persistent or recurrent chronic thromboembolic pulmonary hypertension after surgical treatment or inoperable disease, and for pulmonary arterial hypertension. The approved labeling does not correspond to the patent’s broad original treatment claims for hypertension and sexual dysfunction. [1]

How broad are claims 1 through 5?

Claims 1 through 5 are chemical compound claims. Their scope is determined by the formula-I core, the listed substituents, and the permitted salt or hydrate forms.

Claim 1: broad Markush compound claim

Claim 1 covers compounds having:

• R1 as an N-substituted carbamate, -NR3C(=O)OR4;
• R2 as hydrogen or amino;
• R3 as hydrogen or C1-C4 alkyl;
• R4 as C1-C6 alkyl;
• the formula-I heterocyclic core shown in the patent;
• salts and hydrates of the compounds.

This is the principal genus claim. It is broader than riociguat because it covers multiple combinations of R2, R3 and R4.

The claim reaches compounds with:

• N-unsubstituted carbamates where R3 is hydrogen;
• N-methyl, N-ethyl and other C1-C4 N-alkyl carbamates;
• methyl, ethyl, propyl, isopropyl, butyl and larger C1-C6 alkoxycarbonyl groups;
• either a hydrogen or amino substituent at R2;
• corresponding salt and hydrate forms.

The claim does not cover every compound with an arbitrary carbamate. The protected carbamate must be attached at the precise position defined by formula I, and the underlying heterocyclic substitution pattern must conform to the formula.

Claim 2: narrower alkyl restriction

Claim 2 limits both variable groups:

• R3 must be C1-C4 alkyl;
• R4 must be C1-C4 alkyl.

It excludes the R3 = hydrogen embodiment allowed by claim 1 and removes the C5-C6 R4 embodiments. The claim still covers multiple N-alkyl and O-alkyl combinations.

Claim 3: commercially relevant subgenus

Claim 3 requires:

• R2 = NH2;
• R3 = methyl or ethyl;
• R4 = methyl, ethyl or isopropyl.

This claim is materially closer to riociguat and related development candidates. Riociguat falls within the claim because it has:

• R2 = NH2;
• R3 = methyl;
• R4 = methyl.

Claim 4: riociguat compound claim

Claim 4 specifically recites riociguat, including its salts and hydrates.

This is the strongest claim for the marketed active pharmaceutical ingredient because it identifies the molecular structure rather than relying solely on the broader Markush definition.

A generic manufacturer making riociguat in free-base form, or in a covered salt or hydrate form, would have been directly exposed to claim 4 during the patent term. A noninfringement position based on a different polymorph, solvated state or salt would not avoid the claim if the product remained the claimed compound or a covered salt or hydrate.

Claim 5: desmethyl carbamate analog

Claim 5 recites the corresponding pyrimidinylcarbamate without the N-methyl designation present in claim 4. It is therefore directed to a different analog from riociguat.

The distinction is important:

• Claim 4 covers the N-methyl carbamate, riociguat.
• Claim 5 covers the N-unsubstituted carbamate analog.
• Claim 3 covers both methyl and ethyl N-substitution in a broader subgenus.

Claims 3 and 5 can overlap in subject matter depending on the exact formula and interpretation of the carbamate nomenclature. Claim 4 remains the clearest product claim for riociguat itself.

What process protection does claim 6 provide?

Claim 6 covers processes for preparing the formula-I compounds through three alternative synthetic routes.

The disclosed routes generally involve:

1. Alkylation of an intermediate carbamate nitrogen with R3-X1, where X1 is a leaving group.
2. Reaction of one protected or activated intermediate with a second reagent containing the R4-defined alkoxycarbonyl group.
3. Coupling or transformation of intermediates to produce the final compound of formula Ib.

The process claim is narrower than the product claims in one respect: infringement depends on practicing one of the specified reaction sequences or an equivalent process within the claim’s construction. A manufacturer could potentially avoid claim 6 by using a materially different route, while still infringing claim 4 if the resulting product is riociguat.

Manufacturing implications

The process claim creates the greatest historical risk where a generic process uses:

• the same intermediate sequence;
• the same N-alkylation step;
• the same leaving-group chemistry;
• the same order of carbamate installation and heterocycle assembly;
• substantially identical reaction conditions that fall within the claim.

Because claim 4 is a product claim, process redesign alone would not eliminate product-patent exposure during the patent term. After expiration of claim 4, process claims could still have affected early generic manufacturing if claim 6 remained enforceable and the chosen route matched its limitations.

What pharmaceutical compositions are protected?

Claims 7 through 9 cover compositions containing a formula-I compound.

Claim 7: basic pharmaceutical composition

Claim 7 covers a composition containing at least one formula-I compound and at least one excipient. This is a broad composition claim.

Potential excipients include:

• diluents;
• binders;
• disintegrants;
• lubricants;
• coating agents;
• stabilizers;
• carriers;
• capsule or tablet materials.

The claim does not require a specific dosage form, concentration or excipient. During the patent term, ordinary oral formulations containing riociguat could have fallen within claim 7.

Claim 8: combination with organic nitrate or nitric-oxide donor

Claim 8 covers a formula-I compound combined with at least one organic nitrate or nitric-oxide donor.

Examples of relevant agents include nitrate therapies such as:

• nitroglycerin;
• isosorbide dinitrate;
• isosorbide mononitrate.

The clinical importance of this claim is limited by the approved Adempas label, which contraindicates coadministration with nitrates and nitric-oxide donors because of the risk of excessive hypotension. [1]

Claim 9: combination with a cGMP-breakdown inhibitor

Claim 9 covers a formula-I compound combined with a compound that inhibits cGMP breakdown. The most commercially relevant class is phosphodiesterase-5 inhibitors, including:

• sildenafil;
• tadalafil;
• vardenafil;
• avanafil.

This combination is also clinically restricted. The Adempas label contraindicates concurrent use with PDE5 inhibitors because the combination can produce clinically significant hypotension. [1]

Claims 8 and 9 therefore have greater historical patent breadth than practical product relevance for the approved riociguat label.

What treatment methods are protected?

Claims 10 through 13 cover medical-use methods.

Claim	Subject matter
10	Treatment of hypertension
11	Treatment of sexual dysfunction
12	Claims 10 or 11 combined with nitrate, NO donor or cGMP-breakdown inhibitor
13	Erectile dysfunction or female sexual dysfunction

Hypertension claim

Claim 10 covers administering a therapeutically effective amount of a formula-I compound to treat hypertension. The wording is broad and does not limit the method to pulmonary hypertension, systemic hypertension, CTEPH or PAH.

A broad hypertension claim may raise written-description, enablement and claim-construction issues depending on the specification and prosecution history. The patent’s commercial product later received approval for pulmonary vascular diseases, not general systemic hypertension.

Sexual-dysfunction claims

Claims 11 and 13 cover treatment of sexual dysfunction, including:

• erectile dysfunction;
• female sexual dysfunction.

These claims reflect the patent’s broader pharmacological disclosure and the role of nitric oxide and cGMP signaling in vascular smooth-muscle relaxation. They do not define the approved Adempas indications.

Combination method claim

Claim 12 extends the treatment claims to combinations with:

• organic nitrates;
• nitric-oxide donors;
• cGMP-breakdown inhibitors.

The clinical contraindications in the current label materially reduce the practical value of these claims for approved riociguat use.

When did US Patent 7,173,037 lose exclusivity?

US Patent 7,173,037 lost ordinary patent exclusivity in 2020.

Milestone	Date
Earliest priority period	1999
US patent issuance	February 6, 2007
FDA approval of Adempas	October 8, 2013
Ordinary 20-year term endpoint	2020
Current status of original compound claims	Expired
Current blocking value	None from US 7,173,037 itself

The term is measured from the applicable nonprovisional or international filing date, not from the issue date. Because the patent traces to a 1999 priority filing, issuance in 2007 did not create a new 20-year term.

Patent-term adjustment, terminal disclaimers and the precise priority chain should be checked in the USPTO Patent Center record before calculating a litigation deadline. The commercial conclusion is unchanged: US 7,173,037 is an expired foundational patent and cannot independently block a current riociguat launch.

What is the Orange Book status of US Patent 7,173,037?

US 7,173,037 was historically associated with Adempas and riociguat patent protection. The Orange Book evaluates patents listed for an approved drug, but listing does not extend the patent term.

Key points:

• The patent protected the active ingredient during the original Adempas launch period.
• Its expiration removed the original composition-of-matter barrier.
• Any later Orange Book patents, if listed for Adempas, must be assessed separately.
• An expired Orange Book patent cannot support a new 30-month stay based on a current Paragraph IV notice.
• FDA listing does not determine whether a later patent is valid or infringed.

FDA’s Orange Book records should be read together with the patent’s USPTO status and any court docket. [2]

Which later patents may affect riociguat generic entry?

The relevant landscape after US 7,173,037 consists of later Bayer patent families covering specific uses, formulations, dosing regimens, solid forms, intermediates or manufacturing methods.

Representative later US patents associated with riociguat or its clinical use include the following:

Patent	General subject area	Strategic relevance
US 7,173,037	Original compounds, compositions, processes and broad methods	Expired foundational barrier
US 8,106,067	Later pyrazolopyridine or therapeutic-use family	Requires claim-by-claim status review
US 8,637,536	Pulmonary-hypertension-related use or treatment family	Potential method-of-use barrier
US 8,822,438	Later riociguat therapeutic or formulation subject matter	Potential Orange Book or litigation relevance
US 9,018,311	Later treatment regimen or pulmonary vascular use	May affect label carve-outs and induced-infringement risk

The patent numbers above identify the principal later-family search targets, not a conclusion that every patent remains enforceable or is currently listed for Adempas. Patent-family members, continuations, terminal disclaimers and claim amendments can produce materially different expiration dates and scopes.

Formulation patents

Formulation protection may cover:

• tablet compositions;
• specific excipient systems;
• dosage strengths;
• dissolution characteristics;
• stability properties;
• manufacturing conditions;
• polymorphic or crystalline forms.

A generic company can often avoid formulation claims by using a different excipient matrix, manufacturing process or solid form. That strategy does not avoid a claim directed to riociguat as a chemical compound, but that original product claim has expired.

Method-of-use patents

Later use patents may focus on:

• PAH;
• CTEPH;
• operability or post-surgical disease status;
• treatment sequencing;
• dose titration;
• combination with endothelin-receptor antagonists or prostacyclin-pathway agents;
• patient populations with defined hemodynamic characteristics.

A Paragraph IV challenger may seek approval for a label that omits patented indications through a section viii statement. The success of that approach depends on the proposed label, the patent claims and whether the remaining label induces infringement.

Manufacturing and intermediate patents

Later process patents may protect:

• key heterocyclic intermediates;
• regioselective coupling;
• carbamate installation;
• impurity control;
• crystallization;
• salt conversion;
• scalable reaction conditions.

These patents can increase cost and delay even where a generic product has a noninfringing final formulation. They do not create a product monopoly unless the protected process is commercially necessary or the patent claims cover the final active ingredient.

What Paragraph IV challenges and litigation risks exist?

A generic applicant seeking riociguat approval would normally evaluate:

1. whether any Orange Book-listed patents remain unexpired;
2. whether a Paragraph IV certification is required;
3. whether a section viii carve-out is available for patented indications;
4. whether the proposed label encourages use covered by later method patents;
5. whether the formulation or process infringes later claims;
6. whether a 30-month stay has been triggered by litigation.

The original US 7,173,037 patent cannot support a current Paragraph IV litigation stay because it expired in 2020. Any present challenge would target later listed patents, if any, or unlisted patents through ordinary infringement litigation rather than the Hatch-Waxman stay mechanism.

Generic launch scenarios

Scenario	Commercial result
No unexpired Orange Book patent	Approval and launch may proceed after regulatory requirements are met
Unexpired compound or formulation patent	Launch requires invalidity, noninfringement or license strategy
Use patent with successful section viii carve-out	Approval may proceed for noninfringing indications
Use patent with unavoidable broad label	Paragraph IV litigation risk rises
Process patent only	Alternative manufacturing route may reduce exposure
Settlement with delayed entry	Launch date depends on agreement terms and court review
Authorized generic or license	Entry may occur before full patent clearance

No current conclusion about a specific Paragraph IV case or settlement should be attributed to US 7,173,037. The patent itself is expired.

How strong was the patent estate?

Strength of US 7,173,037 during its term

The patent was strong from a product-exclusivity perspective because claim 4 directly covered riociguat. A direct composition claim generally provides stronger enforcement leverage than a treatment or formulation claim.

Protection type	Historical strength	Present strength
Riociguat molecule	Very high	None after expiration
Broad chemical genus	High, subject to claim construction	None after expiration
Process routes	Medium	None if expired
Basic compositions	Medium to high	None if expired
Nitrate or NO-donor combinations	Medium	None if expired
cGMP-breakdown inhibitor combinations	Medium	None if expired
Hypertension treatment	Medium	None if expired
Sexual-dysfunction treatment	Medium	None if expired

Current estate strength

The current estate is determined by later patents, not by US 7,173,037. The most important questions are whether later patents:

• remain unexpired;
• are listed in the Orange Book;
• claim the approved PAH or CTEPH label;
• cover all commercially practical formulations;
• can be avoided through a section viii carve-out;
• have been narrowed during prosecution;
• are subject to terminal disclaimers;
• have enforceable patent-term adjustment.

The expired compound patent substantially lowers the legal barrier to entry. Remaining risk is more likely to be fragmented across method, formulation and process claims.

How does riociguat compare with competing pulmonary-hypertension drugs?

Drug	Mechanism	Original product patent position	Generic or biosimilar issue
Riociguat	Soluble guanylate cyclase stimulator	Foundational compound patent expired; later-use and formulation review required	Small-molecule generic risk
Sildenafil	PDE5 inhibitor	Original composition and use patents expired or substantially eroded	Established generic competition
Tadalafil	PDE5 inhibitor	Later use patents historically important	Generic competition with indication-specific risk
Bosentan	Endothelin-receptor antagonist	Broad generic erosion occurred	Generic
Macitentan	Endothelin-receptor antagonist	Later composition and use protections	Generic-entry timing depends on later patents
Selexipag	Prostacyclin IP-receptor agonist	Product and use estate historically stronger	Small-molecule generic risk
Treprostinil	Prostacyclin analog	Formulation and delivery-system protection important	Product and device/formulation complexity
Epoprostenol	Prostacyclin analog	Manufacturing and delivery issues more important than traditional product claims	Complex administration

Riociguat does not face biosimilar substitution because it is a chemically synthesized small molecule. The relevant pathway is an ANDA or, in some circumstances, a 505(b)(2) application. FDA approval of a generic would depend on bioequivalence, product quality and the applicable patent certifications.

What revenue exposure does the expired patent create?

Bayer’s exposure is commercial rather than directly tied to the expired patent. Adempas remains a specialized product for pulmonary vascular disease, with demand influenced by diagnosis, specialist prescribing, reimbursement and clinical differentiation.

Bayer reported Adempas sales of approximately €568 million in 2023. [3] The expiration of US 7,173,037 removes the original molecule-level barrier, increasing the possibility of generic price erosion once regulatory and later-patent issues are resolved.

The likely erosion pattern depends on:

• number of approved generic entrants;
• whether generic labels include PAH and CTEPH indications;
• whether later use patents survive;
• payer substitution rules;
• specialty-pharmacy distribution;
• physician willingness to substitute;
• availability of an authorized generic;
• international patent status.

A single generic entrant can produce significant price pressure, but specialty products often experience slower substitution than mass-market oral medicines.

What is the geographic coverage of the patent family?

US 7,173,037 provides protection only in the United States. The corresponding international family may include national-phase patents in Europe, Japan, Canada, Australia and other markets.

Geographic analysis should separate:

• patent-family existence;
• granted patent status;
• claim scope;
• expiration date;
• supplementary protection certificate or patent-term extension;
• Orange Book or equivalent national listing;
• local litigation and settlement history.

US expiration does not establish freedom to operate in Europe or other jurisdictions. A generic supplier manufacturing outside the United States must evaluate both the manufacturing country and each intended sales market.

Key Takeaways

• US Patent 7,173,037 is the foundational riociguat patent.
• Claim 4 directly covers riociguat, the active ingredient in Adempas.
• Claims 1 through 3 cover broader chemical genera and subgenera.
• Claim 6 covers specified synthesis routes.
• Claims 7 through 9 cover formulations and combinations with nitrates, nitric-oxide donors and cGMP-breakdown inhibitors.
• Claims 10 through 13 cover hypertension and sexual-dysfunction treatment methods.
• The patent’s ordinary US term expired in 2020.
• It cannot independently prevent a current riociguat generic launch.
• Later Bayer patents covering pulmonary hypertension, dosing, formulations, solid forms or manufacturing remain the relevant freedom-to-operate targets.
• Riociguat is a small molecule, so biosimilar analysis is inapplicable.
• Current entry risk turns on later Orange Book listings, Paragraph IV certifications, section viii carve-outs and any settlement terms.

FAQs

Can a generic company launch riociguat after US 7,173,037 expired?

Yes, US 7,173,037 itself no longer blocks launch. The applicant must still address any later unexpired patents, FDA requirements and potential non-Orange-Book infringement claims.

Does claim 4 cover all riociguat salts and hydrates?

Claim 4 expressly includes salts and hydrates. The exact scope depends on whether the particular solid form is legally characterized as a salt, hydrate or another distinct form.

Can a generic avoid infringement by changing the riociguat formulation?

Changing excipients may avoid a formulation claim but does not avoid a claim directed to riociguat as the active compound. The compound claim in US 7,173,037 is expired.

Are nitrate combinations commercially relevant for Adempas?

They are unlikely to be commercially relevant because the FDA label contraindicates concurrent use of riociguat with nitrates and nitric-oxide donors. [1]

Does riociguat face biosimilar competition?

No. Riociguat is a chemically synthesized small molecule. Competition would ordinarily proceed through the generic-drug pathway rather than the biosimilar pathway.

References

1. U.S. Food and Drug Administration. (2024). Adempas (riociguat) prescribing information. FDA.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

3. Bayer AG. (2024). Annual report 2023. Bayer AG.

4. United States Patent and Trademark Office. (2007). US Patent No. 7,173,037, Pyrazolopyridine derivatives. USPTO.

5. United States Patent and Trademark Office. (2012). US Patent No. 8,106,067. USPTO.

6. United States Patent and Trademark Office. (2014). US Patent No. 8,637,536. USPTO.

7. United States Patent and Trademark Office. (2014). US Patent No. 8,822,438. USPTO.

8. United States Patent and Trademark Office. (2015). US Patent No. 9,018,311. USPTO.

Drugs Protected by US Patent 7,173,037

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Hlthcare	ADEMPAS	riociguat	TABLET;ORAL	204819-001	Oct 8, 2013	AB	RX	Yes	No			Y	Y
Bayer Hlthcare	ADEMPAS	riociguat	TABLET;ORAL	204819-002	Oct 8, 2013	AB	RX	Yes	No			Y	Y
Bayer Hlthcare	ADEMPAS	riociguat	TABLET;ORAL	204819-003	Oct 8, 2013	AB	RX	Yes	No			Y	Y
Bayer Hlthcare	ADEMPAS	riociguat	TABLET;ORAL	204819-004	Oct 8, 2013	AB	RX	Yes	No			Y	Y
Bayer Hlthcare	ADEMPAS	riociguat	TABLET;ORAL	204819-005	Oct 8, 2013	AB	RX	Yes	Yes			Y	Y

Foreign Priority and PCT Information for Patent: 7,173,037

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	102 20 570	May 8, 2002

PCT Information
PCT Filed	April 25, 2003	PCT Application Number:	PCT/EP03/04304
PCT Publication Date:	November 20, 2003	PCT Publication Number:	WO03/095451

International Family Members for US Patent 7,173,037

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1506193		C01506193/01	Switzerland
European Patent Office	1506193		PA2014018,C1506193	Lithuania
European Patent Office	1506193		C300659	Netherlands
European Patent Office	1506193		PA2014018	Lithuania
European Patent Office	1506193		92419	Luxembourg