Details for Patent: 11,007,156

Summary for Patent: 11,007,156

Title:	Prolonged release pharmaceutical composition containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol
Abstract:	A pharmaceutical formulation for prolonged release of the active ingredient 3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol or a pharmaceutically acceptable salt thereof in a matrix containing between 1 and 80 wt. % of at least one pharmaceutically acceptable hydrophilic or hydrophobic polymer as a matrix forming agent and exhibiting in vivo the following release rate: 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours; 5 to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour; 10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours; 15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours; 30 to 97% by weight 3-(3-dimethylaminol-1-ethyl-2-methyl-propyl)phenol released after 6 hours; more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours; more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours.
Inventor(s):	Johannes Bartholomaeus, Iris Ziegler
Assignee:	Gruenenthal GmbH
Application Number:	US16/600,974
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

United States Patent 11,007,156: Tapentadol Extended-Release Formulation Scope, Validity, and Patent Landscape

U.S. Patent No. 11,007,156 protects slow-release oral formulations of tapentadol, particularly matrix tablets using high-viscosity cellulose polymers. Its broadest issued formulation claims require a defined in-vivo time to peak plasma concentration, while claim 1 adds a detailed dissolution profile. The patent is directed to formulation technology rather than tapentadol as a molecule.

The patent is commercially relevant to Nucynta ER and other twice-daily tapentadol extended-release products. It does not create biosimilar risk because tapentadol is a chemically synthesized small molecule. Generic risk is governed by ANDA certifications, Orange Book listings, formulation design-around options, and the enforceability of the release-profile and pharmacokinetic limitations.

What drug and technology does U.S. Patent 11,007,156 protect?

The active ingredient identified in the patent is tapentadol, chemically described as 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol. The claims cover the racemate, pharmaceutically acceptable salts, and the individual stereoisomers identified in claims 9, 10, 20 and 21.

The invention is a hydrophilic or otherwise cellulose-based matrix system designed to produce prolonged oral release. The specified matrix polymers include:

• Hydroxypropylmethylcellulose, or HPMC
• Hydroxyethylcellulose
• Hydroxypropylcellulose, or HPC
• Methylcellulose
• Ethylcellulose
• Carboxymethylcellulose

The independent claims impose different protection layers:

Claim	Principal subject matter	Key limiting feature
1	Slow-release formulation	Cellulose matrix, defined dissolution profile, 2-10 hour peak plasma level, polymer viscosity of 3,000-150,000 mPa·s
12	Slow-release formulation	Cellulose matrix, 2-10 hour peak plasma level, polymer viscosity of 3,000-150,000 mPa·s
11	Tablet	Tablet containing the claim 1 formulation, for twice-daily administration
22	Tablet	Tablet containing the claim 12 formulation, for twice-daily administration
23	Method of treatment	Twice-daily administration of a claim 11 tablet for pain
24	Method of treatment	Twice-daily administration of a claim 22 tablet for pain

Claim 12 is structurally important because it omits claim 1’s detailed in-vitro dissolution profile. A competing product may therefore avoid claim 1 while still implicating claim 12 if it uses the specified cellulose matrix, viscosity range and pharmacokinetic profile.

What are the broadest claims in U.S. Patent 11,007,156?

Claim 12 is the broadest formulation claim in practical terms. It requires four central elements:

1. Tapentadol or a pharmaceutically acceptable salt.
2. A slow-release oral formulation.
3. A matrix containing 1% to 40% by weight of one or more specified cellulose matrix-forming agents.
4. An in-vivo peak plasma concentration occurring approximately 2 to 10 hours after administration.
5. Matrix-polymer viscosity of 3,000 to 150,000 mPa·s in a 2% aqueous solution at 20°C.

Claim 1 contains the same general formulation architecture but adds a cumulative release profile measured by the European Pharmacopoeia paddle method at 75 rpm, pH 6.8 and 37°C.

The claim 1 release windows are:

Time after testing begins	Tapentadol released
0.5 hours	3% to 35%
1 hour	5% to 50%
2 hours	10% to 75%
3 hours	15% to 82%
6 hours	30% to 97%
12 hours	More than 50%
18 hours	More than 70%
24 hours	More than 80%

The formulation must satisfy every recited release limitation. A product outside any one of the specified ranges may have a noninfringement argument against claim 1, although it could remain exposed under claim 12 or another family patent.

How do the dependent claims narrow the patent scope?

Claims 2 through 10 narrow claim 1. Claims 13 through 21 repeat substantially the same narrowing structure for claim 12.

The main narrowing categories are:

Polymer viscosity

The viscosity limitations create three nested ranges:

Claim set	Viscosity range
Claims 1 and 12	3,000-150,000 mPa·s
Claims 2 and 13	10,000-150,000 mPa·s
Claims 3 and 14	50,000-150,000 mPa·s
Claims 25 and 26	HPMC at approximately 100,000 mPa·s

Claims 25 and 26 are commercially significant because HPMC with an approximately 100,000 mPa·s viscosity is a common high-viscosity grade for robust hydrophilic matrix tablets. Those claims are narrower but may be easier to prove against a product using a corresponding polymer grade.

Polymer identity

Claims 4 and 15 restrict the matrix agent to HPMC, hydroxyethylcellulose or HPC. This removes methylcellulose, ethylcellulose and carboxymethylcellulose from the claimed alternatives.

Drug loading

The drug-loading limitations are:

• 0.5% to 85% active ingredient and 8% to 40% matrix agent in claims 5 and 16.
• 3% to 70% active ingredient and 10% to 35% matrix agent in claims 6 and 17.
• 8% to 66% active ingredient and 10% to 30% matrix agent in claims 7 and 18.

The nested concentration ranges are directed to conventional high-dose matrix tablets and could capture commercially practical formulations even if a generic manufacturer varies excipient levels.

Pharmacokinetics

Claims 8 and 19 narrow the peak plasma concentration, or Tmax, to 3.5 to 6 hours. This is materially narrower than the 2-to-10-hour range in claims 1 and 12.

A generic applicant could seek to design around the narrower dependent claims by producing a formulation with a Tmax outside 3.5 to 6 hours. That strategy would not necessarily avoid the broader 2-to-10-hour limitation.

What is the claim-construction risk for the dissolution limitations?

The dissolution limitations are potentially valuable but technically burdensome.

Claim 1 specifies:

• Ph. Eur. Paddle Method
• 75 rpm
• Buffer meeting Ph. Eur. requirements
• pH 6.8
• 37°C
• UV-spectrometric detection
• Release percentages at eight time points

The test method provides an objective framework, but enforcement would require reliable testing of the accused product under materially identical conditions. Relevant disputes could involve:

• Buffer composition and ionic strength.
• Paddle geometry and apparatus qualification.
• Sink conditions.
• Tablet-to-tablet variability.
• Whether percentages are calculated against labeled dose, assay value or recovered active ingredient.
• UV interference from excipients or degradation products.
• Sampling correction and replacement volume.
• Whether the release profile must satisfy each time point independently.

The claim also contains an apparent typographical error in one release limitation, referring to “3-(3-dimethylaminol-ethyl-2-methyl-propyl)phenol.” The surrounding claim language identifies tapentadol consistently. A court would likely analyze the error under claim-construction principles, prosecution history and the specification rather than treat the typographical defect in isolation.

What formulation designs could avoid U.S. Patent 11,007,156?

Potential design-around routes include:

Design-around approach	Primary claim element targeted	Residual risk
Noncellulosic matrix	Specified cellulose Markush group	Other formulation patents may cover alternative polymers
Cellulose polymer below 3,000 mPa·s	Viscosity threshold	Functional release or method-of-use claims may remain
Polymer above 150,000 mPa·s	Upper viscosity threshold	Manufacturing and tablet-performance issues
Nonmatrix extended-release system	“Active ingredient in a matrix”	Coating, osmotic or multiparticulate patents may apply
Tmax below 2 hours or above 10 hours	Pharmacokinetic limitation	Product may fail twice-daily performance objectives
Release profile outside one or more claim 1 ranges	Dissolution limitations	Claim 12 does not require the detailed release profile
Different tapentadol salt or stereochemical composition	Active-ingredient limitation	Claims broadly cover pharmaceutically acceptable salts and both named enantiomers
Once-daily or non-tablet dosage form	Twice-daily tablet claims	Broad formulation claims 1 and 12 may still apply

The strongest design-around is generally a genuinely noncellulosic extended-release architecture that also produces a pharmacokinetic profile outside the claimed Tmax range. A mere change in tablet shape, compression force, excipient grade or coating thickness would not necessarily avoid the claims.

When does U.S. Patent 11,007,156 lose exclusivity?

The patent issued on May 18, 2021. Its statutory term is tied to the earliest effective nonprovisional priority filing in the relevant family, not to the grant date. The patent belongs to the tapentadol sustained-release formulation family associated with Grünenthal.

The family’s commercial formulation patents generally trace to a 2007 priority period. On that basis, the ordinary 20-year term runs into 2027 or 2028, subject to the controlling USPTO term calculation, patent-term adjustment and any applicable terminal disclaimer. Patent expiration does not by itself establish generic launch permission because other Orange Book-listed patents, pediatric exclusivity or litigation settlements may affect entry.

Milestone	Date or period
Relevant formulation-family priority	2007 period
U.S. patent grant	May 18, 2021
Ordinary 20-year term	2027-2028 period, depending on controlling priority date
Pediatric exclusivity	Must be checked against the applicable NDA and Orange Book
Patent-term adjustment	Must be taken from the USPTO patent record
Generic entry	Controlled by all remaining applicable patents and exclusivities

The exact expiration date should be taken from the USPTO continuity and patent-term records for Patent No. 11,007,156 and its parent applications. The grant date alone cannot be used to calculate expiration.

What is the FDA and Orange Book status of the patent?

Nucynta ER is an FDA-approved extended-release tapentadol product. The reference product is marketed for severe, persistent pain requiring an around-the-clock opioid analgesic, subject to the product labeling and opioid-related regulatory controls. FDA approval does not mean that every formulation patent is listed in the Orange Book.

Orange Book relevance depends on whether the patent claims:

• The approved drug substance.
• The approved drug product.
• A formulation or composition of the approved drug.
• An approved method of use.

U.S. Patent 11,007,156 is a formulation patent. Its relevance to Orange Book listing depends on the patent-listing submission made by the NDA holder and FDA’s acceptance of that submission. A patent may be commercially important without appearing in the Orange Book if its claims do not satisfy FDA listing standards or if the NDA holder did not submit it.

The applicable FDA regulatory framework is Hatch-Waxman. An ANDA applicant must address each listed patent through one of the following certifications:

• Paragraph I: no patent information has been submitted.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will wait until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable or will not be infringed.

A Paragraph IV notice can trigger a 45-day period for the patent owner or NDA holder to file an infringement action. A timely action generally creates a 30-month stay of final FDA approval, subject to statutory exceptions and court developments [1, 2].

Which companies are challenging tapentadol extended-release exclusivity?

The principal competitive threat comes from ANDA applicants seeking approval for generic tapentadol extended-release tablets. Public FDA approval and litigation records must be reviewed patent by patent because:

• Not every ANDA filer is publicly identified before litigation.
• A Paragraph IV notice may remain commercially confidential until suit is filed.
• Settlements can provide authorized or licensed launch dates.
• An ANDA may challenge only selected patents while accepting others.
• A later-filed formulation patent may not be listed against an earlier ANDA.

The relevant competitive group includes established generic manufacturers with opioid manufacturing and controlled-substance distribution capabilities. Potential participants include large U.S. and international generic companies, but a definitive list of active challengers requires current FDA and PACER records.

What patent litigation and settlement issues affect generic launch?

Litigation exposure should be separated into four categories:

1. Claims directed to tapentadol itself.
2. Claims directed to immediate-release products.
3. Claims directed to extended-release formulations.
4. Claims directed to methods of treating pain.

Patent 11,007,156 is most relevant to the third and fourth categories. Claims 23 and 24 are method claims requiring twice-daily administration for pain. Method claims can create infringement issues when an ANDA label expressly directs the claimed dosing regimen. Their practical value depends on the approved label, induced-infringement evidence and any carve-out language.

Settlement agreements may establish:

• A licensed generic launch date.
• An authorized-generic arrangement.
• Restrictions on formulation, strength or indication.
• A no-challenge provision.
• Acceleration provisions tied to patent invalidity or commercial launch.
• Waivers or covenants relating to specific patents.

A settlement involving a parent patent does not necessarily resolve exposure under Patent 11,007,156 unless the agreement expressly includes it or its continuation and divisional family members.

How strong is the patent estate for tapentadol extended-release products?

The patent estate is strongest where a product uses all of the following:

• Tapentadol or a covered salt.
• A conventional hydrophilic cellulose matrix.
• HPMC or HPC at high viscosity.
• Drug loading within the nested claimed ranges.
• A Tmax between 2 and 10 hours.
• A twice-daily tablet.
• A dissolution profile matching claim 1.

The estate is weaker against:

• Nonmatrix delivery systems.
• Multiparticulate systems with distinct release mechanisms.
• Noncellulosic polymers.
• Formulations engineered outside the claimed pharmacokinetic window.
• Products with a different approved dosing schedule.
• Products whose in-vitro release profile clearly falls outside claim 1.

The patent’s functional limitations create both strength and vulnerability. They can capture formulations that differ in quantitative composition but perform in the claimed manner. They also create proof requirements that can support noninfringement defenses if the release test or in-vivo Tmax falls outside the claim.

How does Patent 11,007,156 compare with molecule and product patents?

Protection category	Target	Relevance to generic entry
Compound patent	Tapentadol molecule	Usually the earliest and strongest barrier, if unexpired
Salt or stereoisomer patent	Specific chemical form	May narrow exposure to selected products
Immediate-release formulation patent	Nucynta IR-type product	Does not necessarily block extended-release products
Extended-release formulation patent	Matrix, coating or release profile	Directly relevant to Nucynta ER substitutes
Method-of-use patent	Pain treatment and dosing	Depends on label language and induced infringement
Manufacturing patent	API or tablet production	Can create supply-chain barriers
Patent 11,007,156	Cellulose matrix plus PK and, in claim 1, dissolution profile	Direct product-specific formulation risk

Patent 11,007,156 should therefore be analyzed as one layer in a multi-patent estate. It should not be treated as a substitute for a complete Orange Book, continuity, litigation and settlement review.

What manufacturing and intellectual-property barriers remain?

The formulation claims may constrain generic development even when a formal design-around is possible. High-viscosity HPMC systems can create manufacturing issues involving:

• Blend uniformity at high drug loading.
• Granulation and compression.
• Tablet swelling and erosion.
• Content uniformity.
• Dissolution reproducibility.
• Scale-up from laboratory to commercial equipment.
• Stability in different humidity conditions.
• Controlled-substance manufacturing and distribution requirements.

A noninfringing formulation must also satisfy FDA requirements for bioequivalence, impurities, stability, dissolution similarity where applicable, and abuse-deterrence or opioid-label obligations if relevant to the product.

The commercial barrier is therefore broader than the patent claims. A design-around that avoids the cellulose matrix may require a new formulation development program and new bioequivalence work.

What revenue exposure does the patent create?

Nucynta ER revenue exposure is concentrated in the extended-release tapentadol market. Patent risk affects:

• The duration of branded pricing.
• The timing of generic substitution.
• Inventory and contracting strategy.
• Authorized-generic economics.
• Controlled-substance manufacturing capacity.
• Forecasts for opioid-product revenue after patent expiry.

The patent does not independently determine brand revenue. Revenue protection depends on the combined term of the compound, formulation and method-of-use patents, regulatory exclusivities, ANDA litigation outcomes and settlement terms.

Key Takeaways

• U.S. Patent 11,007,156 covers tapentadol slow-release oral formulations using specified cellulose matrix polymers.
• Claim 12 is the broadest formulation claim because it requires the pharmacokinetic Tmax limitation but not claim 1’s detailed dissolution profile.
• Claim 1 is narrower but provides a technically specific release-profile barrier.
• Claims 25 and 26 target HPMC with approximately 100,000 mPa·s viscosity and may be important against conventional high-viscosity matrix tablets.
• The patent covers formulation technology, not tapentadol as a chemical compound.
• Generic developers may pursue noncellulosic, nonmatrix or pharmacokinetically distinct formulations.
• Tapentadol is a small molecule, so biosimilar risk does not apply. The relevant pathway is ANDA approval.
• Paragraph IV exposure depends on current Orange Book listings, ANDA notices, litigation and settlement agreements.
• The patent’s effective term is tied to the family’s 2007 priority period and ordinarily extends into the 2027-2028 period, subject to the USPTO term record.
• A complete launch assessment requires review of the entire tapentadol patent family rather than Patent 11,007,156 alone.

FAQs About U.S. Patent 11,007,156 and Tapentadol ER

Does Patent 11,007,156 cover Nucynta ER by brand name?

No. The claims use chemical, formulation, dissolution and pharmacokinetic limitations. A Nucynta ER product may fall within the claims if its composition and performance satisfy those limitations.

Can a generic use HPMC and avoid Patent 11,007,156?

Possibly, but only if the complete formulation falls outside the applicable viscosity, amount, dissolution or pharmacokinetic limitations. Using a different HPMC grade alone may not avoid infringement.

Does a different tapentadol salt avoid the patent?

Not necessarily. The claims expressly cover tapentadol and pharmaceutically acceptable salts. The salt must be evaluated against the claim language and the product’s formulation characteristics.

Are claims 23 and 24 relevant to a generic with a carved-out label?

They can be. A label carve-out may reduce method-of-use exposure, but it does not eliminate infringement risk under the composition and formulation claims.

Is Patent 11,007,156 more important than the original tapentadol compound patent?

That depends on expiration and enforceability. An unexpired compound patent generally presents a broader barrier, while Patent 11,007,156 can extend or preserve product protection after compound protection ends if the formulation claims remain enforceable.

References

1. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
2. U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Refuse-to-receive standards. https://www.fda.gov/drugs
3. U.S. Patent and Trademark Office. (2021). U.S. Patent No. 11,007,156, sustained release formulation of tapentadol. https://patents.google.com/patent/US11007156B2
4. U.S. Food and Drug Administration. (2024). Nucynta ER prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
5. World Intellectual Property Organization. (2008). Patent family records for sustained-release tapentadol formulations. PATENTSCOPE. https://patentscope.wipo.int/

Drugs Protected by US Patent 11,007,156

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

International Family Members for US Patent 11,007,156

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1439829		C20110003 00036	Estonia
European Patent Office	1439829		99 1-2011	Slovakia
European Patent Office	1439829		C 2011 002	Romania
Argentina	036943
Argentina	104921
Austria	303802
Brazil	0213653