Details for Patent: 8,808,737

Which drugs does patent 8,808,737 protect, and when does it expire?

Patent 8,808,737 protects OPANA ER and is included in two NDAs.

Summary for Patent: 8,808,737

Title:	Method of treating pain utilizing controlled release oxymorphone pharmaceutical compositions and instruction on dosing for renal impairment
Abstract:	The invention pertains to a method of using oxymorphone in the treatment of pain by providing a patient with an oxymorphone dosage form and informing the patient or prescribing physician that the bioavailability of oxymorphone is increased in patients with renal impairment.
Inventor(s):	Harry Ahdieh
Assignee:	Endo Operations Ltd
Application Number:	US12/716,973
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,808,737
Patent Claim Types: see list of patent claims	Use; Dosage form;

Scope and claims analysis for US Patent 8,808,737 (oxymorphone renally impaired controlled-release pain dosing by AUC/Cmax cutoffs)
US 8,808,737 is a US method-of-treatment patent focused on renal impairment–guided dose selection for an immediate-concentrate, solid oral controlled-release oxymorphone product, using creatinine clearance (CrCl) stratification plus post-dose systemic exposure limits (12-hour AUC and/or Cmax). Claim scope is tightly anchored to: (i) oxymorphone as the sole active ingredient in a controlled-release solid oral dosage form (5–80 mg), (ii) dosing decisions driven by CrCl bands (<30; 30–50; 51–80; >80 mL/min), and (iii) pharmacokinetic exposure thresholds after administration (AUC0–12 <21, <20, <19 ng·hr/mL and/or Cmax <1.4, <1.3, <1.2 ng/mL). This structure is designed to deter both “label-adjacent” renally impaired titration and generic/bioequivalent designs that overshoot systemic exposure in kidney-compromised patients.

What patents protect oxymorphone controlled-release dosing in renally impaired patients under creatinine clearance?

Answer: US 8,808,737 protects method-of-treatment steps combining CrCl measurement, renally dependent dose reduction, and post-dose exposure limits in renally impaired patients for oxymorphone controlled-release solid oral dosage forms. The independent claim requires all elements in combination, plus an AUC0–12 cutoff; dependent claims narrow the cutoff further. An alternate independent claim replaces AUC with a Cmax cutoff.

What is the protected method under Claim 1 (AUC-based threshold)?

Claim 1 elements (all required):

1. Treat pain in a renally impaired patient.
2. Provide a solid oral controlled release dosage form containing:
   • oxymorphone or pharmaceutically acceptable salt
   • 5 mg to 80 mg
   • sole active ingredient
   • a controlled release matrix
3. Measure creatinine clearance and categorize into one of four bands:
   • (a) less than about 30 mL/min
   • (b) about 30 mL/min to about 50 mL/min
   • (c) about 51 mL/min to about 80 mL/min
   • (d) above about 80 mL/min
4. Orally administer a lower dosage depending on which band applies, “to provide pain relief.”
5. After administration, the average AUC of oxymorphone over a 12-hour period is < about 21 ng·hr/mL.

Claim 2 and 3 narrow Claim 1’s AUC threshold:

• Claim 2: AUC0–12 < 20 ng·hr/mL
• Claim 3: AUC0–12 < 19 ng·hr/mL

What is the protected method under Claim 4 (Cmax-based threshold)?

Claim 4 elements (all required):
Same CrCl-measurement and lower-dosage logic for renally impaired pain treatment using the same controlled-release oxymorphone solid oral dosage form, but with the exposure metric changed to:

• After administration, average Cmax of oxymorphone < about 1.4 ng/mL

Claim 5 and 6 narrow Claim 4’s Cmax threshold:

• Claim 5: Cmax < 1.3 ng/mL
• Claim 6: Cmax < 1.2 ng/mL

Claim construction hotspots likely to drive infringement and validity fights

Key claim-interpretation pressure points in US practice:

“Solid oral controlled release dosage form”

• Requires an oral, solid dosage form with controlled release behavior.
• A court often focuses on whether the accused product has a release profile consistent with “controlled release” as understood in the intrinsic record.
• The claim ties to a “controlled release matrix,” limiting the likely acceptable dosage technologies to matrix-type release structures, not pure reservoir implants or purely diffusion-independent profiles.

“Controlled release matrix”

• This phrase is narrower than generic “controlled release formulation.”
• A challenger would argue the accused dosage form does not use a matrix (for example, multi-particulate systems or coated pellets inside a tablet can create dispute: whether the pellets constitute the “matrix” and whether the claim requires a unitary matrix).

“Oxymorphone as the sole active ingredient”

• This limits the claim to formulations where no other pharmaceutically active compound is included.
• Combinations are outside scope.

CrCl banding and “in dependence on which…rate is found”

• The method is not “treat renally impaired pain” in general. It requires a dosing decision that is explicitly dependent on which CrCl band applies.
• A label that uses e.g., eGFR staging rather than CrCl could be litigated on “creatinine clearance” equivalence versus strict literal requirement.

PK metric: “average” and “over a 12-hour period”

• Claim 1’s AUC requirement is specifically 12-hour and uses an “average.”
• “Average” could mean mean across patients in a study. For infringement, the patentee typically needs to show the accused use protocol yields the threshold in the relevant population or that the method is practiced in such a way that the patient population necessarily yields the threshold.

Exposure thresholds are the infringement lock

• The AUC and Cmax cutoffs function as the core novelty.
• This design supports enforceability against products or dosing regimens that maintain safety in renal impairment by limiting systemic exposure.

Which steps and parameters does US 8,808,737 require to be practiced for infringement?

Answer: In the US, infringement of these claims requires practicing each step category in combination: CrCl measurement, dosage reduction based on one of four CrCl bands, and achieving post-dose exposure below a specified AUC0–12 (Claim 1 family) or Cmax (Claim 4 family) using a solid oral controlled-release oxymorphone formulation containing 5–80 mg oxymorphone with a controlled release matrix.

Step-by-step infringement checklist (practical operationalization)

1. Identify a renally impaired patient being treated for pain.
2. Confirm the administered product is a solid oral controlled release oxymorphone product with:
   • 5–80 mg oxymorphone (or salt)
   • sole active ingredient
   • controlled release matrix
3. Confirm the prescribing/dispensing routine includes measuring CrCl and mapping it to the claimed bands.
4. Confirm the administered dose is “a lower dosage” based on which band the CrCl falls into.
5. Confirm the achieved PK exposure metric in that use context is below:
   • AUC0–12 < 21 ng·hr/mL (Claim 1), with dependent narrowing to 20 or 19
   • or Cmax < 1.4 ng/mL (Claim 4), with dependent narrowing to 1.3 or 1.2

What counts as “renally impaired” in a claim-driven CrCl framework?

The patent’s CrCl bands implicitly define renal impairment for the method. The lowest band includes CrCl <30 mL/min; other bands cover moderate impairment and above. The claim does not limit “renally impaired” to one band, because CrCl categories include >80 mL/min. That drafting choice suggests renal-status control is part of dosing strategy across a range, not only severe impairment.

When does US 8,808,737 expire, and what exclusivity timelines matter for generic entry?

Answer: This cannot be completed from the provided inputs. The expiration date depends on filing date, earliest effective filing, patent term adjustments, and any terminal disclaimers. Without those data, a precise expiration and exclusivity timeline would be incomplete.

What is the Orange Book status of oxymorphone controlled-release renally impaired dosing patents like US 8,808,737?

Answer: This cannot be completed from the provided inputs. Orange Book status requires the listed drug product and the patent-to-product linkage (US patent numbers on the Orange Book), which are not provided.

How strong is the patent estate for renally impaired oxymorphone controlled-release methods of treatment?

Answer: Based on claim structure alone, the estate strength is driven by (i) the specificity of CrCl band dosing and (ii) the objective PK exposure ceilings. This typically makes validity and infringement harder to attack than broad “dose reduction” claims, because challengers must find prior art disclosing the same combination of renal stratification and the same exposure limits, or must show the accused product/dosing cannot achieve those ceilings.

Strength indicators embedded in the claim text

1. Combination claim logic: CrCl measurement + banding + dose reduction + controlled-release oxymorphone dosage form + exposure metric. Combination claims can be harder to anticipate than single-variable prior art.
2. Objective pharmacokinetic cutoffs: AUC0–12 and Cmax thresholds provide measurable targets, which can support nonobviousness and narrower infringement.
3. Dependent claim tightening: Additional AUC/Cmax thresholds (21→20→19; 1.4→1.3→1.2) create multiple “fall-back” infringement positions.

Vulnerability indicators embedded in the claim text

1. “Average” and population variability: If the exposure in practice varies, defendants may attack whether the accused method necessarily yields “average” below the cutoff.
2. Controlled-release matrix limitation: If a competitor uses a different controlled-release architecture, they can argue non-infringement on the matrix limitation.
3. Creatinine clearance vs eGFR labeling: If renal assessment in the accused regimen is based on eGFR rather than CrCl, there can be a literal-stepping issue.

How does US 8,808,737 compare with other oxymorphone renally impaired dose adjustment patents (AUC vs Cmax coverage)?

Answer: Within the claims you provided, the patent has two independent claim tracks that map to two standard PK control points:

• AUC0–12 control (Claims 1–3)
• Cmax control (Claims 4–6)

This dual-track architecture is strategically important. Defendants cannot easily design around by matching only one PK endpoint. If a dosing change reduces Cmax but increases AUC (or vice versa), they may still fall within one independent claim.

What design-around strategies are implied by the split

• A formulation designer could target either AUC or Cmax reductions through slower release, altered dissolution, or changed dose. The claim pair reduces room to maneuver: both endpoints are plausibly linked to release profile, but not always in a monotonic way.
• A dosing regimen designer could alter dose selection per CrCl bands to keep exposure under threshold.

What generic entry risks exist for controlled-release oxymorphone in renally impaired patients?

Answer: The primary generic entry risk under this patent is not generic chemical identity. It is whether a generic controlled-release oxymorphone product, when dosed according to CrCl band protocols and used in renally impaired pain patients, produces systemic exposure that stays below the claimed AUC0–12 or Cmax thresholds.

Risk profile by claim track

• AUC-based risks (Claims 1–3): If clinical use results in mean AUC0–12 ≥21 ng·hr/mL (or ≥20 / ≥19 for dependent positions), the method steps do not meet the claim limitation. Conversely, if the accused dosing protocol yields exposure below the threshold, the risk rises.
• Cmax-based risks (Claims 4–6): A generic that “matches” overall exposure but slightly elevates early peak levels may fail the Cmax limitation. That could provide a potential design gap for a defendant, depending on which independent claim the patentee asserts.

Practical litigation posture

Patentees typically proceed on:

• evidence that the accused product’s release profile plus renal dosing instructions yields PK outcomes below the cutoffs, and/or
• evidence that prescribing behavior in routine practice follows the claimed CrCl-band algorithm.

Defendants typically counter with:

• alternative renal stratification approaches,
• differences in dosage form release architecture versus “controlled release matrix,” and
• PK evidence demonstrating thresholds are not met.

What would a Paragraph IV strategy likely target against US 8,808,737?

Answer: From claim scope alone, a Paragraph IV challenger would focus on at least one required limitation failing in the accused method. Likely attack lines:

1. Non-infringement

   • formulation not a “controlled release matrix”
   • CrCl not measured or not used to dose per claimed bands
   • dosing does not reduce dose based on the band
   • observed mean AUC0–12 or mean Cmax in claimed use is not below thresholds

2. Invalidity

   • prior art describing renal impairment dose adjustments for opioids generally could be insufficient if it does not disclose the specific PK cutoffs tied to oxymorphone controlled-release matrix products
   • anticipatory prior art would need to disclose both the CrCl band logic and the exposure ceilings (or an equivalent set of disclosures enabling the same measured endpoints)

Does US 8,808,737 cover method-of-use only, or does it also impact formulations and manufacturing?

Answer: On the claim text provided, protection is method-of-treatment and dosing-by-renal-status, not a manufacturing method claim. It does indirectly constrain formulation design because the method requires a specific dosage form structure (solid oral controlled release with controlled release matrix, 5–80 mg oxymorphone, sole active ingredient).

What formulation-level design changes could avoid “controlled release matrix”

A competitor could attempt to show that its controlled-release system does not meet the “controlled release matrix” limitation. That typically turns on formulation architecture and how the intrinsic record defines “matrix.”

What clinical protocol changes could avoid CrCl-band dependence

A competitor could attempt to show that clinical dosing is not “in dependence on” the exact CrCl categories, such as using different renal endpoints or different renal staging cutoffs.

How many claims does US 8,808,737 protect, and what is their relevance to litigation value?

Answer: Based only on the excerpt, at least six claims exist in the scope you provided: independent Claim 1 and Claim 4, each with dependent claims tightening AUC or Cmax cutoffs. Without the full claim list, the count and remaining coverage cannot be established from provided inputs.

Key Takeaways

• US 8,808,737 is a renal-impairment dosing method patent for solid oral controlled-release oxymorphone using CrCl banding and post-dose exposure ceilings.
• Claim 1 family: requires AUC0–12 <21 ng·hr/mL (with dependent cutoffs <20 and <19).
• Claim 4 family: requires Cmax <1.4 ng/mL (with dependent cutoffs <1.3 and <1.2).
• The patent is likely enforced against prescribing and dosing regimens that match the CrCl-to-dose logic and yield systemic exposure below those thresholds with a controlled-release matrix oxymorphone formulation.

FAQs

1) Does US 8,808,737 require a specific creatinine clearance measurement method or only the numeric CrCl value?
The claims require measuring creatinine clearance and categorizing the patient into the stated numeric bands.

2) Can a product with additional active ingredients infringe?
No, the dosage form must have oxymorphone (or its salt) as the sole active ingredient.

3) If a generic matches the label dose but slightly exceeds the AUC cutoff, is it outside the claim?
For infringement of Claim 1/2/3, the method requires average AUC0–12 below the specific threshold.

4) Are both AUC and Cmax required for infringement?
No. Claims are structured as two independent tracks: AUC-limited (Claims 1–3) or Cmax-limited (Claims 4–6).

5) Does the patent cover immediate-release oxymorphone?
The method requires a solid oral controlled-release dosage form with a controlled release matrix, so immediate-release products do not meet that limitation as written.

References

(Only sources cited inline would be listed here. No external sources were used in this response.)

Drugs Protected by US Patent 8,808,737

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 Operations	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	021610-001	Jun 22, 2006		DISCN	Yes	No	8,808,737					DOSE MODIFICATION FOR RENAL IMPAIRMENT
Endo Operations	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	021610-005	Feb 29, 2008		DISCN	Yes	No	8,808,737					DOSE MODIFICATION FOR RENAL IMPAIRMENT
Endo Operations	OPANA ER	oxymorphone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	021610-002	Jun 22, 2006		DISCN	Yes	No	8,808,737					DOSE MODIFICATION FOR RENAL IMPAIRMENT