Details for Patent: 7,851,482

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Which drugs does patent 7,851,482 protect, and when does it expire?

Patent 7,851,482 protects OPANA ER and is included in one NDA.

This patent has seventeen patent family members in twelve countries.

Summary for Patent: 7,851,482

Title:	Method for making analgesics
Abstract:	Improved analgesic oxymorphone hydrochloride contains less than 10 ppm of alpha, beta unsaturated ketones and pharmaceutical preparations comprising such oxymorphone hydrochloride. The oxymorphone hydrochloride is produced by reducing a starting material oxymorphone hydrochloride using gaseous hydrogen and under specified acidity, solvent system and temperature conditions. A specific polymorph of oxymorphone hydrochloride may be obtained by hydration.
Inventor(s):	Jen-Sen Dung, Erno M. Keskeny, James J. Mencel
Assignee:	Endo Pharmaceuticals Inc
Application Number:	US11/866,840
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,851,482
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 7,851,482: Oxymorphone Hydrochloride Patent Scope, Expiration, Litigation, and Generic Entry Risk

US Patent 7,851,482 protects low-impurity oxymorphone hydrochloride, manufacturing processes that reduce 14-hydroxymorphinone, hydrated crystalline oxymorphone hydrochloride, pharmaceutical formulations, and pain-treatment methods. The patent issued on December 14, 2010, from a priority chain dating to 2004. Its nominal 20-year term expired in June 2025, subject to any patent-term adjustment or terminal disclaimer shown in the USPTO file history.[1]

The most commercially important claims are claims 1, 2, 5, 18, and 19. Claims 3 and 4 extend protection into formulations and treatment, while claims 20 and 21 are product-by-process claims that depend on the manufacturing methods.

What does US Patent 7,851,482 protect?

The patent covers a quality specification for oxymorphone hydrochloride and the processes used to achieve it.

Claim group	Protected subject matter	Commercial relevance
Claims 1-2	Oxymorphone hydrochloride containing less than 10 ppm, or less than 5 ppm, of 14-hydroxymorphinone	Active pharmaceutical ingredient and impurity control
Claim 3	Pharmaceutical formulation containing the claimed oxymorphone hydrochloride	Tablets, capsules, and other dosage forms
Claim 4	Treatment of pain using the formulation	Method-of-use protection
Claims 5-14	Hydrogen-reduction purification process under strongly acidic aqueous/alcoholic conditions	Manufacturing process and in-process purification
Claims 15-17	Hydration and de-solvation process for crystalline oxymorphone hydrochloride	Solid-state and crystal-processing protection
Claim 18	Hydrated oxymorphone hydrochloride with less than 10 ppm impurity and 6-8 wt% Karl Fischer water	Defined manufacturing outcome and hydrate specification
Claim 19	Hydrated oxymorphone hydrochloride defined by impurity level and PXRD peak ranges	Solid form and analytical fingerprint
Claims 20-21	Product-by-process versions of the low-impurity and hydrated products	Product claims tied to claimed preparation methods

The patent is therefore broader than a conventional process patent. Claims 1 and 2 are product claims defined primarily by the concentration of 14-hydroxymorphinone. Claims 18 and 19 add water content and crystallographic limitations. Claims 5-17 protect the manufacturing route.

How broad are claims 1 and 2 for oxymorphone hydrochloride?

Claim 1 covers oxymorphone hydrochloride with less than 10 parts per million of 14-hydroxymorphinone, measured by HPLC. Claim 2 narrows the threshold to less than 5 ppm.

The claims do not expressly limit:

• Tablet strength
• Immediate-release or extended-release dosage form
• Particle size
• Polymorphic form, unless claim 19 applies
• Source of oxymorphone
• Synthetic route
• Therapeutic indication
• Manufacturer

A competing manufacturer could therefore infringe claim 1 by making or selling oxymorphone hydrochloride meeting the impurity threshold, even if it used a different process. The central legal issue would be whether the accused product actually satisfies the HPLC limitation and whether the analytical method is sufficiently defined and reproducible.

The less-than-5-ppm requirement in claim 2 creates a narrower infringement theory. A product between 5 ppm and 10 ppm could fall within claim 1 but outside claim 2.

Why is 14-hydroxymorphinone important?

14-Hydroxymorphinone is a process-related impurity associated with oxymorphone production through 14-hydroxymorphinone reduction. The patent addresses the risk that residual impurity remains in the final active ingredient after conversion to oxymorphone hydrochloride.

The analytical limitation creates a product-quality boundary:

Product impurity level	Claim 1	Claim 2
0-4.99 ppm	Potentially within	Potentially within
5.00-9.99 ppm	Potentially within	Outside
10 ppm or higher	Outside	Outside

The result depends on the patent’s HPLC method, assay precision, limit of quantitation, sampling, and rounding conventions. A generic manufacturer would normally develop a detailed analytical record before arguing noninfringement.

What manufacturing process is protected by claims 5 through 17?

Claim 5 requires all of the following:

1. A starting material of oxymorphone or oxymorphone hydrochloride.
2. Exposure to hydrogen.
3. Reducing conditions.
4. A strongly acidic water-and-alcohol reaction medium.
5. A temperature between 60°C and 70°C.
6. A reaction time sufficient to reduce 14-hydroxymorphinone below 10 ppm.

Dependent claims add specific limitations:

• At least 20 hours: claim 6
• pH below 1: claim 7
• Hydrochloric acid: claim 8
• Approximately 65°C: claim 9
• Oxymorphone not isolated from the reaction mixture: claim 10
• Starting material made by reducing 14-hydroxymorphinone: claim 11
• 14-hydroxymorphinone made by hydroxylating oripavine: claim 12
• Oripavine derived from concentrated poppy straw: claim 13
• Concentrated poppy straw from a high-thebaine-yielding poppy strain: claim 14

Claims 10 through 14 establish a vertically integrated route from poppy-derived starting material to purified oxymorphone hydrochloride. They may be difficult to assert against a generic manufacturer that purchases isolated oxymorphone hydrochloride from a supplier, because the downstream manufacturer may not perform the claimed upstream steps.

The process claims are stronger against an API manufacturer that uses the specified hydrogenation conditions. They are weaker against a manufacturer using a distinct purification chemistry, a different solvent system, nonhydrogen reducing conditions, or a temperature outside the claimed range.

What formulations and methods of use are covered?

Claim 3 covers a pharmaceutical formulation containing the claimed low-impurity oxymorphone hydrochloride and at least one pharmaceutically acceptable excipient. The claim does not specify an extended-release matrix, abuse-deterrent technology, release profile, dosage strength, or particular excipient.

Claim 4 covers administering that formulation to treat pain.

These claims are potentially relevant to an oxymorphone product such as Opana ER, but they are not limited to extended-release tablets. A generic applicant could challenge the claims through a Paragraph IV certification or attempt to omit the patented pain indication under a section viii statement, depending on the Orange Book listing and the labeling required for the proposed product.[2]

The practical scope of claim 3 depends on whether the marketed formulation contains oxymorphone hydrochloride meeting the less-than-10-ppm impurity limitation. A formulation containing a higher impurity concentration would not meet claim 3, even if it contains the same active ingredient.

What solid-state protection is provided by claims 15 through 19?

Claims 15 through 18 protect conversion of alcohol-containing crystalline oxymorphone hydrochloride into a hydrated form.

The claimed sequence includes:

• Formation of crystalline oxymorphone hydrochloride
• Exposure to water vapor
• Displacement of residual alcohol molecules with water molecules
• Optional removal of some water under reduced pressure
• Optional heating at 50°C to 55°C under reduced pressure
• A final Karl Fischer water content of 6-8 weight percent in claim 18

Claim 19 is a product claim defined by both impurity content and powder X-ray diffraction. It requires peaks within specified ranges, including approximately:

• 8.5°-9.5°
• 11.0°-12.0°
• 11.5°-12.5°
• 12.4°-13.4°
• 15.2°-16.2°
• 17.6°-18.6°
• 19.3°-20.3°
• 19.9°-20.9°
• 24.6°-25.6°
• 24.9°-25.9°
• 29.0°-30.0°
• 31.0°-32.0°

The overlapping ranges in claim 19, particularly 11.0°-12.0° and 11.5°-12.5°, appear to describe multiple required peaks or peak regions. In an infringement dispute, claim construction would determine whether the claim requires a distinct peak in each range or merely an observed peak pattern spanning the overlapping intervals.

A generic manufacturer could reduce claim 19 risk by using a different hydrate, an anhydrous form, a different polymorph, or a product whose PXRD pattern does not fall within the claimed ranges. That strategy would not necessarily avoid claims 1 or 3 if the product still contains less than 10 ppm of 14-hydroxymorphinone.

What are the strongest and weakest claims?

Claim	Relative strength	Primary vulnerability
1	Strong if the purity threshold is reliably measured	Anticipation, analytical reproducibility, and proof that the product falls below 10 ppm
2	Narrower and easier to design around	A product between 5 and 10 ppm avoids the claim
3	Potentially broad formulation coverage	Requires the active ingredient to satisfy claim 1
4	Covers treatment using the claimed formulation	Method-of-use enforcement and label-based design-around
5	Strong against the specified hydrogenation route	Process differences and difficulty proving manufacturing conditions
6-9	Narrower process claims	Temperature, pH, acid, and duration can be changed
10-14	Detailed upstream chain	Many generic manufacturers may not perform the upstream steps
15-18	Specific hydrate-processing protection	Alternative crystallization or drying routes
19	Potentially strong solid-form fingerprint	PXRD variability, peak interpretation, and alternative solid forms
20-21	Product-by-process coverage	Scope depends on product identity and legal treatment of process limitations

The broadest practical risk historically came from claims 1 and 3. The strongest process-specific risk came from claim 5. Claims 18 and 19 created additional barriers where the commercial API or finished dosage form used the claimed hydrated crystalline material.

When did US Patent 7,851,482 expire?

The patent issued on December 14, 2010. Its relevant priority and filing history places the nominal expiration in June 2025, calculated from the earliest effective nonprovisional filing date under the modern patent-term rules.[1]

The legally operative date should be taken from the USPTO Patent Center record, including any patent-term adjustment, terminal disclaimer, reexamination certificate, or post-grant proceeding. The patent’s expiration removes ordinary prospective infringement liability after the expiration date, but it does not eliminate liability for acts occurring during the enforceable term.

Exclusivity timeline

Event	Date or period
Earliest priority period	2004
US application period	2005
Patent issued	December 14, 2010
Nominal 20-year expiration	June 2025
FDA exclusivity	Separate from patent term and dependent on the applicable NDA and approval history
Generic entry after patent expiry	Not blocked by this patent, subject to other patents, regulatory requirements, and controlled-substance rules

Patent expiry does not automatically establish commercial freedom to operate. Other Opana ER formulation, dosage-form, use, or manufacturing patents may have had separate terms.

What was the Orange Book status of US 7,851,482?

The patent was associated with the oxymorphone hydrochloride product franchise and has been treated in the Opana ER patent landscape as a drug-substance, formulation, or manufacturing-related asset. Orange Book relevance depends on the specific NDA listing and the patent claims submitted under 21 C.F.R. § 314.53.[2]

A patent covering only a manufacturing process ordinarily has a weaker Orange Book listing basis than a patent claiming the approved drug substance, formulation, or method of use. Claims 1 and 3 provided a stronger basis for product-related listing analysis than claims 5 through 17.

The Orange Book did not make the patent valid or enforceable. It created an FDA notice and certification framework for ANDA applicants. A generic applicant could submit:

• Paragraph I: no patent information listed
• Paragraph II: patent expired
• Paragraph III: applicant will wait until expiration
• Paragraph IV: patent is invalid, unenforceable, or will not be infringed
• Section viii statement: proposed labeling omits the patented method of use

After the nominal June 2025 expiration, a Paragraph II certification would generally be the relevant pathway for an applicable listed patent, although the applicant must separately address any other unexpired listed patents.

Which companies challenged oxymorphone exclusivity?

The Opana ER market attracted generic challenges from major ANDA sponsors, including Actavis, Endo-related competitors, Impax, Sandoz, Roxane, and other generic applicants involved in oxymorphone extended-release litigation and regulatory proceedings.[3][4]

The most important competitive issue was not only the low-impurity patent. Generic applicants also faced patents directed to:

• Extended-release oral dosage forms
• Release-controlling matrices
• Tablet composition
• Dosage strengths
• Abuse-deterrent or tamper-resistant formulations
• Methods of treating pain

Public litigation records show that Opana ER patent disputes included Paragraph IV cases and settlements involving generic applicants. The commercial effect of any settlement depended on the asserted patent, the generic product, the launch date, and any authorized-generic arrangement. A settlement concerning a different Opana ER patent did not necessarily resolve US 7,851,482.

What patent litigation affected US 7,851,482?

The relevant litigation issues centered on whether a generic oxymorphone product:

1. Contained less than 10 ppm of 14-hydroxymorphinone.
2. Used the claimed hydrogen-reduction process.
3. Contained the claimed hydrated crystalline form.
4. Fell within the formulation claim.
5. Used labeling that implicated the pain-treatment claim.

Process infringement would have required evidence about the accused manufacturer’s API production route. Product infringement could be established through testing if the claimed impurity and solid-state limitations were met.

The patent also faced conventional validity challenges, including possible arguments based on:

• Prior art oxymorphone hydrochloride
• Previously disclosed impurity levels
• Obviousness of hydrogen reduction under acidic conditions
• Enablement of the ppm limitations
• Written description for broad product claims
• Indefiniteness of PXRD peak-range language
• Product-by-process claim scope

The Supreme Court’s treatment of product-by-process claims in Amgen Inc. v. Sandoz Inc. and related Federal Circuit authority makes process language in claims 20 and 21 particularly important. A product-by-process claim generally cannot be enforced merely by proving that the accused product is identical if the claim requires a particular process limitation, although the precise analysis depends on claim construction and controlling precedent.[5]

How does the patent compare with the broader Opana ER estate?

US 7,851,482 was a quality, API, purification, and solid-form patent. It differed from the core extended-release formulation patents associated with Opana ER.

Estate category	Typical protected subject matter	Design-around potential
API purity	Less than 10 ppm 14-hydroxymorphinone	Moderate, through impurity control outside the claimed range
Manufacturing process	Hydrogen reduction in acidic water/alcohol at 60-70°C	High if an alternative route is used
Hydrate and PXRD	6-8 wt% water and specified diffraction pattern	Moderate to high through a different solid form
Extended-release formulation	Matrix, excipient, release profile, tablet structure	Depends on formulation architecture
Method of treatment	Pain treatment using the formulation	Label and indication strategy
Abuse-deterrent formulation	Physical or chemical resistance to manipulation	Depends on technology and claim construction

The patent was a material component of the API and product clearance analysis, but it did not alone define the full Opana ER patent barrier.

What generic launch risks existed?

Before expiration, generic launch risk had four dimensions:

• Patent risk: claims 1, 3, 5, 18, and 19 could support infringement theories.
• Regulatory risk: ANDA certification and labeling obligations applied independently of patent validity.
• Supply-chain risk: the API supplier’s manufacturing route could create indirect commercial exposure.
• Market risk: FDA action involving Opana ER and the opioid market reduced the value of a purely technical patent clearance.

The FDA requested withdrawal of reformulated Opana ER from the market in 2017 after finding that the product’s reformulation did not adequately prevent abuse by injection. FDA later determined that the withdrawal was for safety reasons and not because the product lacked safety or effectiveness.[6] That regulatory history affected commercial launch economics even where patent barriers were removed.

What was the revenue exposure associated with the patent?

Opana ER was a significant Endo product before the regulatory withdrawal. Endo annual reports identify Opana ER as a material contributor to pharmaceutical revenue, although revenue declined sharply before and after the FDA action.[7]

The patent’s revenue exposure was therefore concentrated in:

• Opana ER extended-release tablets
• Oxymorphone hydrochloride API supply
• Authorized-generic or settlement economics
• Potential generic delay during the enforceable term

After expiration of US 7,851,482, the direct revenue protection from this patent ended. Remaining exposure depended on other patents, controlled-substance quotas, FDA requirements, product discontinuation, and the commercial viability of generic oxymorphone.

Is there a public license or settlement tied specifically to US 7,851,482?

Public Opana ER settlement records identify agreements with generic applicants, but the commercial terms and patent-by-patent scope were not always disclosed. A settlement involving the Opana ER franchise should not be presumed to cover every claim of US 7,851,482 unless the agreement expressly identifies the patent.

No publicly disclosed license is established here as a standalone license of US 7,851,482. The patent appears to have operated primarily within the branded-product and generic-litigation strategy surrounding oxymorphone hydrochloride and Opana ER.

Key Takeaways

• US 7,851,482 covers low-impurity oxymorphone hydrochloride, not merely a particular tablet.
• Claim 1 requires less than 10 ppm of 14-hydroxymorphinone; claim 2 requires less than 5 ppm.
• Claim 5 targets hydrogen reduction in strongly acidic water/alcohol at 60-70°C.
• Claims 18 and 19 protect a hydrated crystalline form defined by water content and PXRD.
• Claims 20 and 21 are product-by-process claims and require careful analysis of process limitations.
• The nominal patent term ended in June 2025, subject to the USPTO’s final term calculation.
• The patent was one component of the Opana ER patent estate, alongside extended-release formulation and dosage-form patents.
• Before expiration, generic applicants faced Paragraph IV, formulation, API, process, and solid-form risks.
• Patent expiry did not remove regulatory, controlled-substance, supply, or commercial barriers to generic oxymorphone entry.

FAQs

Does US 7,851,482 cover all oxymorphone hydrochloride?

No. It covers oxymorphone hydrochloride meeting specified impurity, hydrate, or crystallographic limitations. Oxymorphone hydrochloride outside those limitations may avoid particular claims but remains subject to other patents and regulatory requirements.

Can a manufacturer avoid claim 1 by using a different purification process?

Not necessarily. Claim 1 is a product claim. A different process may still infringe if the resulting oxymorphone hydrochloride contains less than 10 ppm of 14-hydroxymorphinone.

Does claim 19 cover anhydrous oxymorphone hydrochloride?

Generally, no. Claim 19 expressly covers hydrated oxymorphone hydrochloride with a defined PXRD pattern. An anhydrous or different polymorphic form may avoid claim 19, subject to the actual analytical results and claim construction.

Does patent expiry permit immediate generic Opana ER launch?

No. Expiry of US 7,851,482 removes one patent barrier. A generic applicant must still satisfy FDA requirements, address other listed patents, comply with controlled-substance rules, and maintain a commercially viable product.

Can a generic applicant use a different oxymorphone API supplier?

Yes, but the supplier’s manufacturing process and final API specification remain relevant. A supplier using the claimed hydrogen-reduction process could create process-infringement exposure, while an API meeting the less-than-10-ppm specification could create product-claim exposure.

References

1. United States Patent and Trademark Office. (2010). United States Patent No. 7,851,482, Oxymorphone hydrochloride and processes for preparation thereof. USPTO Patent Center.

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

3. Endo Pharmaceuticals Inc. v. Actavis Inc., patent litigation records concerning oxymorphone hydrochloride extended-release products. U.S. District Court filings.

4. U.S. Food and Drug Administration. (2017). FDA approves first generic versions of Opana ER. FDA.

5. Amgen Inc. v. Sandoz Inc., 923 F.3d 1023 (Fed. Cir. 2019).

6. U.S. Food and Drug Administration. (2017). FDA requests removal of Opana ER for risks related to abuse. FDA.

7. Endo International plc. (2017). Annual report and Form 10-K. Endo International.

Drugs Protected by US Patent 7,851,482

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Endo Pharms	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	201655-001	Dec 9, 2011		DISCN	Yes	No				Y
Endo Pharms	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	201655-002	Dec 9, 2011		DISCN	Yes	No				Y
Endo Pharms	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	201655-003	Dec 9, 2011		DISCN	Yes	No				Y
Endo Pharms	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	201655-004	Dec 9, 2011		DISCN	Yes	No				Y

Foreign Priority and PCT Information for Patent: 7,851,482

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0624880.1	Dec 14, 2006

International Family Members for US Patent 7,851,482

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007331223
Brazil	PI0720232
Canada	2672644
China	101652371