Details for Patent: 10,835,515

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Which drugs does patent 10,835,515 protect, and when does it expire?

Patent 10,835,515 protects NUBEQA and is included in one NDA.

This patent has fifteen patent family members in thirteen countries.

Summary for Patent: 10,835,515

Title:	Carboxamide derivative and its diastereomers in stable crystalline form
Abstract:	The present disclosure relates to solid crystalline forms of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) and the diastereomers thereof, and to methods for preparing such crystalline forms. Compound (I) and the diastereomers thereof are potent androgen receptor (AR) modulators useful as a medicament.
Inventor(s):	Olli Törmäkangas, Terhi Heikkinen
Assignee:	Orion Oyj
Application Number:	US16/458,435
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,835,515
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent 10,835,515: Darolutamide Crystal Form I Patent Scope and Patent Landscape

U.S. Patent No. 10,835,515 protects oral tablets and capsules containing crystalline Form I of darolutamide, together with treatment of prostate cancer using those dosage forms. The patent does not broadly claim darolutamide as a chemical compound. Its commercial value rests on solid-state protection directed to the specific polymorph used in an oral pharmaceutical product.

The patent was granted to Orion Corporation and is associated with the Nubeqa (darolutamide) product marketed by Bayer and Orion. Its term is expected to extend into December 2036, subject to any applicable patent-term adjustment or terminal disclaimer. The patent is separate from earlier compound patents covering darolutamide itself.

What drug does U.S. Patent 10,835,515 protect?

U.S. Patent 10,835,515 protects crystalline Form I of darolutamide, also known by the chemical name:

N-[(S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl]-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide.

Darolutamide is a nonsteroidal androgen-receptor inhibitor. Bayer markets it in the United States as Nubeqa, currently for specified prostate-cancer indications in combination with androgen-deprivation therapy, including nonmetastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer when used with docetaxel in the approved regimen. The FDA approved Nubeqa in July 2019 and later expanded its labeling to metastatic hormone-sensitive disease.[1]

Item	Details
Active ingredient	Darolutamide
Brand	Nubeqa
Drug class	Androgen-receptor inhibitor
Dosage form	Oral tablet
U.S. NDA	212099
Original FDA approval	July 30, 2019
Patent analyzed	U.S. 10,835,515
Patent type	Solid-state, dosage-form, and method-of-treatment claims
Patent owner/assignee	Orion Corporation
Commercial partners	Orion and Bayer
Expected nominal expiration	December 2036, subject to patent-term adjustment

What are the claims of U.S. Patent 10,835,515?

The patent has three claims, with independent claims directed to the dosage form and treatment method.

Claim 1: Oral dosage form containing Form I

Claim 1 covers:

• a tablet or capsule;
• for oral administration;
• containing crystalline Form I of darolutamide;
• with a specified X-ray powder diffraction pattern; and
• together with a pharmaceutical excipient.

The claim requires characteristic XRPD peaks at approximately:

• 8.5 degrees 2-theta;
• 10.4 degrees 2-theta;
• 16.6 degrees 2-theta;
• 16.9 degrees 2-theta; and
• 24.3 degrees 2-theta.

This is a product claim directed to a finished pharmaceutical dosage form. It is not limited to a particular excipient, tablet weight, coating, dissolution profile, manufacturing process, or clinical dose.

The phrase "comprising" gives the claim open-ended scope. A product containing the listed Form I material and at least one pharmaceutical excipient can fall within the claim even if it includes additional active ingredients, excipients, coatings, stabilizers, or processing aids, unless another claim limitation is absent.

Claim 2: Additional XRPD limitations

Claim 2 depends on claim 1 and requires five additional approximate XRPD peaks:

• 9.7 degrees 2-theta;
• 15.9 degrees 2-theta;
• 19.2 degrees 2-theta;
• 21.8 degrees 2-theta; and
• 25.5 degrees 2-theta.

Claim 2 is narrower than claim 1. It may provide a more specific crystallographic fingerprint for Form I and create a separate infringement position if an accused product satisfies the additional peak limitations but disputes the broader characterization in claim 1.

Claim 3: Prostate-cancer treatment

Claim 3 covers a method of treating prostate cancer by administering a therapeutically effective amount of the dosage form in claim 1 or claim 2.

The treatment claim incorporates the dosage-form and Form I limitations. It does not claim every method of treating prostate cancer with darolutamide. A method using a different polymorph, amorphous darolutamide, or a formulation that does not contain the claimed dosage form may fall outside claim 3, depending on the evidence and claim construction.

What is the practical scope of the Form I crystal claim?

The patent's central limitation is the identity of the solid form, not merely the chemical identity of darolutamide.

A generic or competing product is most exposed if it:

1. contains darolutamide in crystalline Form I;
2. supplies the drug in a tablet or capsule;
3. includes a conventional pharmaceutical excipient; and
4. produces the claimed XRPD peak pattern.

The claim does not require the marketed Nubeqa formulation to be duplicated exactly. A different tablet hardness, coating, dose strength, excipient system, manufacturing site, or release profile may still infringe if the dosage form contains the claimed Form I.

What does the claim not expressly require?

The claims do not expressly require:

• a 300-mg or 600-mg strength;
• a particular excipient;
• a specific dissolution specification;
• a particular tablet coating;
• a particular particle-size distribution;
• a particular polymorphic purity;
• a particular manufacturing process;
• use with androgen-deprivation therapy;
• use with docetaxel;
• treatment of nonmetastatic castration-resistant prostate cancer; or
• treatment of metastatic hormone-sensitive prostate cancer.

Those omissions increase the potential breadth of claim 1. The claim is tied to the dosage form and crystal identity rather than to the commercial label or one clinical regimen.

How important are the XRPD limitations?

The XRPD limitations are both a scope limitation and an infringement-testing mechanism.

A solid-form claim generally turns on whether the accused material has the claimed crystalline structure. XRPD is used to compare diffraction peaks generated by the accused material with the patent's listed peaks. The word "about" permits some analytical tolerance, but it does not eliminate the need to show that the accused material has the claimed structural characteristics.

The critical technical issues include:

• instrument calibration;
• radiation source;
• sample preparation;
• preferred orientation;
• peak-position tolerance;
• peak intensity;
• detection of mixtures of polymorphs;
• hydration or solvation state; and
• whether formulation excipients interfere with the diffraction pattern.

The claim recites selected characteristic peaks rather than a complete XRPD pattern. That can complicate both infringement and validity analysis. A court may need to determine whether the listed peaks, read in the context of the specification, identify Form I with sufficient precision and whether the word "about" provides an objectively ascertainable boundary.

What formulations are protected by U.S. 10,835,515?

The patent protects oral tablets and capsules containing Form I darolutamide with a pharmaceutical excipient.

Covered formulation categories

Potentially covered products include:

• immediate-release tablets;
• film-coated tablets;
• capsules;
• tablets containing multiple excipients;
• tablets with different strengths;
• products made by direct compression;
• products made by granulation; and
• products containing additional active ingredients.

The claims do not appear limited to the specific marketed Nubeqa tablet composition. A generic manufacturer therefore may not avoid claim 1 merely by changing the coating, filler, binder, disintegrant, lubricant, tablet size, or manufacturing process.

Potentially outside the claim

Products may have a stronger noninfringement position if they use:

• a noncrystalline or amorphous form of darolutamide;
• a different crystalline polymorph that lacks the claimed peaks;
• a salt, solvate, or co-crystal outside the claimed Form I identity;
• a liquid formulation rather than a tablet or capsule; or
• a dosage form without a pharmaceutical excipient, although that design would be commercially unusual.

A formulation that contains a mixture of Form I and another form presents a fact-intensive issue. The open-ended "comprising" language may allow additional solid forms, but the product must still contain the claimed Form I material in the claimed dosage form.

When does U.S. Patent 10,835,515 expire?

The patent was granted on November 17, 2020. Its expected nominal expiration is in December 2036 based on the underlying priority and U.S. patent-term calculation. The exact Orange Book expiration date should be taken from the current FDA listing because patent-term adjustment, terminal disclaimers, or corrections can affect the final date.

Milestone	Date
Earliest reported priority	December 2015
U.S. patent application family	2016 filing period
U.S. grant	November 17, 2020
Expected nominal expiration	December 2036
NCE exclusivity for Nubeqa	Expired in 2024
Current commercial relevance	Patent protection remains after NCE expiry

The NCE exclusivity period and the patent term are separate. Nubeqa's five-year new chemical entity exclusivity did not eliminate the later-expiring Form I patent. Generic applicants could begin preparing and filing ANDAs after the applicable exclusivity restrictions ended, but launch remains subject to listed patents, Paragraph IV litigation, settlements, and any 30-month stay.

What is the Orange Book status of U.S. Patent 10,835,515?

The patent is associated with Nubeqa's U.S. regulatory patent estate and is relevant to FDA-approved oral darolutamide products. Orange Book listings should be checked against the current FDA electronic Orange Book because listing status, use codes, and expiration information can change.

The patent is materially different from a broad active-ingredient patent:

• an active-ingredient patent generally covers darolutamide itself;
• a formulation patent covers a defined composition or dosage form;
• a solid-form patent covers a specified polymorph;
• a method-of-use patent covers treatment of a listed disease or patient population.

U.S. 10,835,515 combines solid-form and dosage-form protection, with a treatment-method claim dependent on the dosage-form claims. Its listing value is therefore strongest against an ANDA product that uses the same crystalline form in an oral tablet or capsule.

How does the patent compare with other darolutamide patents?

Darolutamide's patent estate includes several protection layers.

Protection layer	Typical subject matter	Relevance to generic entry
Compound patent	Darolutamide chemical structure	Broadest chemical protection
Solid-form patent	Crystalline Form I and XRPD profile	Targets polymorph used in oral product
Formulation patents	Excipients, dosage composition, release properties	May require design-around
Method-of-use patents	Prostate-cancer treatment	Relevant to labeling and induced-infringement risk
Manufacturing patents	Preparation, crystallization, or purification	Can restrict supply-chain options
Regulatory exclusivity	NCE and possible pediatric exclusivity	Delays ANDA approval independently of patents

The compound patent is generally the most important early barrier. U.S. Patent 10,835,515 becomes more important after compound-patent expiry because it can extend practical protection for the commercial solid form.

A generic manufacturer that avoids Form I may still face other patents covering darolutamide, approved uses, formulation features, or manufacturing methods. Conversely, invalidating or designing around the solid-form claims does not necessarily clear the entire Nubeqa estate.

What are the principal validity risks?

The patent's validity will depend on the priority disclosure, written description, enablement, anticipation, obviousness, and claim construction.

Anticipation

An anticipation challenge would require a single prior-art reference to disclose the claimed dosage form containing darolutamide Form I and the specified XRPD characteristics. A reference that discloses darolutamide without Form I, or Form I without the claimed dosage form, may not anticipate the full combination.

Obviousness

An obviousness challenge could rely on:

• prior disclosure of darolutamide;
• known polymorphism in pharmaceutical compounds;
• routine crystallization screening;
• a reasonable expectation of identifying a stable form;
• prior art disclosing the Form I diffraction pattern; or
• formulation references teaching tablets or capsules containing darolutamide.

The strongest obviousness case would require more than a general expectation that polymorphs might exist. It would need a persuasive reason to identify this specific Form I and use it in the claimed oral dosage form, together with evidence addressing properties such as stability, manufacturability, bioavailability, or storage performance.

Written description and enablement

Because claim 1 identifies Form I through selected XRPD peaks, a challenger could examine whether the specification adequately identifies and enables the claimed crystalline form across the full scope of "about" the listed peak positions. The written-description issue is stronger if the claim covers a broad analytical range but the specification supports only a narrow sample set.

Indefiniteness

The terms "about" and "characteristic peaks" can raise boundary questions. The specification's experimental methods, peak tolerances, and complete diffraction data will be central to determining whether a skilled person can identify the claimed form with reasonable certainty.

Which companies are challenging Nubeqa patents?

Publicly available information should be separated into two categories:

1. an ANDA filing with a Paragraph IV certification; and
2. a filed district-court infringement action.

A Paragraph IV certification does not itself establish that a generic will launch or that the patent is invalid. It indicates that the applicant asserts that a listed patent is invalid, unenforceable, or not infringed.

The public record for Nubeqa has not established a broadly reported, final generic market entry against U.S. Patent 10,835,515. Any company-specific assessment must be tied to a particular FDA Paragraph IV notice, district-court docket, or settlement agreement. The current public record should not be treated as showing that a successful challenge has eliminated the patent.

What litigation and settlement risks affect generic launch?

A Paragraph IV notice concerning U.S. 10,835,515 could trigger litigation under the Hatch-Waxman Act. If the NDA holder files suit within the statutory period, FDA approval of the ANDA may be stayed for up to 30 months, subject to statutory exceptions and court developments.[3]

Potential outcomes include:

• patent-holder victory and delayed approval;
• generic victory through invalidity or noninfringement;
• settlement with a future launch date;
• license or authorized-generic arrangement;
• dismissal after amendment of the ANDA; or
• resolution based on a narrower product design.

A settlement could permit an agreed launch before the patent expiration date without invalidating the patent. Its commercial effect would depend on the launch date, exclusivity allocation, manufacturing rights, and whether the agreement includes an authorized generic.

What generic entry risks exist for Nubeqa?

The principal generic-entry scenarios are:

Scenario	Effect
Form I tablet or capsule	High direct-infringement exposure under claims 1 and 2
Different polymorph	Possible design-around, subject to other patents
Amorphous darolutamide	Potentially outside claims 1 and 2, but technical and regulatory feasibility must be established
Different excipient system	Usually does not avoid claim 1
Different tablet strength	Usually does not avoid claim 1
Different manufacturing process	Does not avoid a product claim if the resulting product contains Form I
Carved-out label	May reduce method-of-use exposure, but does not avoid product claims
Delayed launch after patent expiry	Lowest litigation risk, subject to other listed patents

The strongest design-around would avoid Form I itself. Changing the excipient system or tablet coating is unlikely to be enough because the claims do not require a particular formulation recipe.

How strong is the patent estate for darolutamide?

U.S. 10,835,515 is a meaningful but specialized patent. Its strength comes from the relationship between the commercial product and the claimed crystal form. If Nubeqa uses Form I and a generic copies that form in an oral tablet, proof of infringement may be more direct than for a narrowly defined formulation patent.

Its limitations are equally clear:

• it does not broadly cover all darolutamide products;
• it may be avoided by a different solid form;
• XRPD testing can create analytical and claim-construction disputes;
• the treatment claim depends on the dosage-form claims;
• invalidity challenges can focus on polymorph obviousness and claim precision; and
• other patents may control launch even if this patent is avoided.

The overall darolutamide estate is stronger than this patent considered alone because compound, solid-form, formulation, use, and manufacturing rights can overlap.

What is the revenue exposure from this patent?

Nubeqa is a major commercial product in Bayer's oncology portfolio, and its revenue base is exposed to the timing of generic entry. U.S. revenue exposure is determined by the combined expiration dates of the compound patent, Form I patent, other listed patents, regulatory exclusivity, and any settlement.

The Form I patent can preserve commercial protection beyond NCE exclusivity and may delay substitution if the marketed product and proposed generic both use Form I. It does not independently guarantee market exclusivity through 2036 because a successful invalidity ruling, noninfringement finding, design-around, license, or settlement could change the launch date.

Public company reporting should be used for current Nubeqa sales and geographic revenue allocation. Patent expiration alone is not a reliable forecast of the date of generic erosion.

What is the geographic coverage of the patent family?

U.S. 10,835,515 provides rights only in the United States. Related applications or counterpart patents may exist in Europe and other jurisdictions, but each jurisdiction has separate:

• claim language;
• prosecution history;
• validity standards;
• patent-term calculation;
• supplementary protection certificate rules;
• litigation record; and
• regulatory listing system.

A U.S. design-around does not establish freedom to operate in Europe, Japan, Canada, China, or other markets. Geographic launch planning requires a country-by-country review of the relevant Form I family members and any SPC or pediatric-extension rights.

What manufacturing and intellectual-property barriers remain after avoiding Form I?

A Form I design-around may still encounter manufacturing barriers. Darolutamide requires control of:

• polymorphic conversion;
• crystallization conditions;
• particle size;
• residual solvents;
• impurities;
• stereochemical purity;
• tablet uniformity; and
• dissolution performance.

A process that begins with another polymorph but converts to Form I during drying, milling, granulation, or storage may create infringement risk. A generic applicant must evaluate the final dosage form, not only the starting material.

Other patent families may also cover synthesis intermediates, purification, crystallization, formulation processing, or combination treatment. Avoiding one solid form does not establish freedom to operate for the entire product.

Key Takeaways

• U.S. Patent 10,835,515 is a darolutamide solid-form patent tied to crystalline Form I.
• Claim 1 covers oral tablets or capsules containing Form I and a pharmaceutical excipient.
• Claim 2 adds five XRPD peaks and is narrower than claim 1.
• Claim 3 covers prostate-cancer treatment using the claimed dosage form.
• The patent does not broadly claim all darolutamide compounds or all darolutamide formulations.
• Changing excipients, coating, strength, or manufacturing process likely will not avoid claim 1 if Form I remains in the final product.
• A different polymorph or amorphous form may provide a design-around, but other darolutamide patents may remain relevant.
• The patent's expected nominal expiration is in December 2036, subject to the official term calculation.
• NCE exclusivity ended in 2024, but patent protection continues beyond that period.
• Generic entry risk depends on the full patent estate, Paragraph IV activity, litigation, settlements, and the solid form used in the ANDA product.

FAQs

Does U.S. Patent 10,835,515 cover Nubeqa by brand name?

No. The claims cover a dosage form containing crystalline Form I of darolutamide, not the Nubeqa trademark. A competing product can infringe without using the Nubeqa name if it contains the claimed Form I in a tablet or capsule.

Can a generic avoid the patent by using different excipients?

Usually not. Claim 1 requires a pharmaceutical excipient but does not require a particular excipient composition. A generic using different fillers, binders, lubricants, disintegrants, or coatings may still infringe if its product contains Form I.

Does a different darolutamide polymorph automatically avoid infringement?

No. A genuinely different polymorph may avoid claims directed to Form I, but the product could still implicate other compound, formulation, method-of-use, or manufacturing patents.

Is the patent relevant to injectable darolutamide?

The asserted claims are directed to a tablet or capsule for oral administration. An injectable product would not satisfy that dosage-form limitation, although separate patents or regulatory requirements could apply.

Can a generic launch after NCE exclusivity expires?

NCE expiry permits the relevant ANDA pathway to proceed, but it does not eliminate unexpired listed patents. A launch may require a Paragraph IV strategy, litigation resolution, license, settlement, or waiting until the relevant patent barriers expire.

References

1. U.S. Food and Drug Administration. (2019). FDA approves darolutamide for non-metastatic castration-resistant prostate cancer. https://www.fda.gov
2. U.S. Food and Drug Administration. (2024). Drugs@FDA: Nubeqa (darolutamide), NDA 212099. https://www.accessdata.fda.gov/scripts/cder/daf/
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
4. U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,835,515: Pharmaceutical dosage form comprising crystalline form I of darolutamide. https://patents.google.com/patent/US10835515
5. Bayer AG. (2024). Annual report 2023. https://www.bayer.com/en/investors/financial-reports
6. Orion Corporation. (2024). Annual report 2023. https://www.orionpharma.com/investors/reports-and-presentations/

Drugs Protected by US Patent 10,835,515

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 Healthcare	NUBEQA	darolutamide	TABLET;ORAL	212099-001	Jul 30, 2019		RX	Yes	Yes			Y			TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC) IN COMBINATION WITH DOCETAXEL
Bayer Healthcare	NUBEQA	darolutamide	TABLET;ORAL	212099-001	Jul 30, 2019		RX	Yes	Yes			Y			TREATMENT OF ADULT PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER (NMCRPC)
Bayer Healthcare	NUBEQA	darolutamide	TABLET;ORAL	212099-001	Jul 30, 2019		RX	Yes	Yes			Y			TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC)

Foreign Priority and PCT Information for Patent: 10,835,515

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Finland	20150033	Jan 30, 2015

International Family Members for US Patent 10,835,515

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Cyprus	1125482
Denmark	3250554
European Patent Office	3250554