Details for Patent: 9,498,486

Which drugs does patent 9,498,486 protect, and when does it expire?

Patent 9,498,486 protects RAYALDEE and is included in one NDA.

This patent has fifty-three patent family members in sixteen countries.

Summary for Patent: 9,498,486

Title:	Method for controlled release oral dosage of a vitamin D compound
Abstract:	A stable, controlled release formulation for oral dosing of vitamin D compounds is disclosed. The formulation is prepared by incorporating one or more vitamin D compounds into a solid or semi-solid mixture of waxy materials. Oral dosage forms can be prepared by melt-blending the components described herein and filling gelatin capsules with the formulation.
Inventor(s):	Charles W. Bishop, Samir P. Tabash, Sammy A. Agudoawu, Jay A. White, Eric J. Messner, P. Martin Petkovich, Keith H. Crawford
Assignee:	Eirgen Pharma Ltd , Opko Health Inc , Opko Renal LLC
Application Number:	US15/231,357
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Executive summary

• US Patent 9,498,486 claims a once-daily extended/sustained-release oral method for treating secondary hyperparathyroidism (sHPT) in CKD using 25-hydroxyvitamin D3 (calcifediol), at 30 µg or 60 µg, with exposure-management limits that avoid transient spikes (explicitly no >3 ng/mL post-dose) and with PK tailoring (extended exposure over ≥4 hours and reduced Cmax24hr/C24hr and/or increased Tmax vs immediate-release).
• Claim scope is concentrated in three “technical pillars”: (1) the clinical target population and end-point (CKD sHPT, PTH reduction), (2) the PK control objective (spike avoidance and dampened peak exposure), and (3) the formulation/technology features (sustained release, and optionally a waxy controlled release carrier with lipoidic agent and oily vehicle).
• From a competitive freedom-to-operate angle, the highest-risk design-arounds for a generic/competitor are those that retain the same PK control objectives while using the same dose range (30/60 µg) and once-daily extended release. The claims include multiple “bridge” claims that can read on different implementation routes (carrier composition, PK metrics, and patient stage).

What is US Patent 9,498,486 and what does it claim for CKD secondary hyperparathyroidism?

US 9,498,486 covers methods of treating secondary hyperparathyroidism in humans with chronic kidney disease using an extended/sustained-release oral dosage form of 25-hydroxyvitamin D (limited in the independent PK-optimized claim set to 25-hydroxyvitamin D3).

Claim architecture (as provided)

• Core independent method claim(s):
  • Claim 1: sustained release oral 25-hydroxyvitamin D to treat sHPT in CKD and reduce serum PTH, while avoiding transient blood level increases >3 ng/mL after a unit dose.
  • Claim 9: sustained release oral 25-hydroxyvitamin D with release over at least four hours (again directed to sHPT in CKD with PTH reduction).
  • Claim 17: sustained release oral 25-hydroxyvitamin D3 with PK profile defined relative to immediate-release via (a) lower Cmax24hr/C24hr and/or (b) increased Tmax vs equivalent immediate-release.
• Dose and regimen limitations threaded through multiple claims:
  • 30 µg or 60 µg
  • once per day
• Patient-stage coverage:
  • CKD Stage 1 or 2
  • CKD Stage 3 or 4
  • CKD Stage 5
• Formulation-technology limitations appear as optional narrowing features in dependent claims:
  • “waxy controlled release carrier”
  • plus lipoidic agent and oily vehicle for the 25-hydroxyvitamin D compound.
• A further independent-style clinical claim (Claim 25) ties product use to a specific treatment niche:
  • adult CKD Stage 3 or 4
  • serum total 25-hydroxyvitamin D <30 ng/mL
  • dose 30 µg or 60 µg, extended release oral, once daily
  • disease is sHPT.

What are the independent claim elements that define infringement risk?

1. Therapeutic target and patient context
   • Human with CKD and secondary hyperparathyroidism
2. Drug identity
   • 25-hydroxyvitamin D (general in claim 1/9; explicitly 25-hydroxyvitamin D3 in claim 17/18/19 and claim 25 and related dependent claims)
3. Dosage form and release
   • sustained release / extended release oral formulation
   • release duration ≥4 hours is explicitly required in claim 9
4. PK objective / limiter
   • avoids >3 ng/mL transient increases after a unit dose (claims 1 and 11, and also 19 on the PK-optimized claim set)
   • and in claim 17, relative PK shaping metrics vs immediate-release:
     • reduced Cmax24hr/C24hr
     • and/or increased Tmax
5. Dose and dosing frequency
   • multiple claims lock to 30 µg or 60 µg and once daily, creating narrower but still meaningful infringement hooks

How broad are the claims: PK-spike avoidance vs release-over-time vs PK-shape relative to immediate-release?

Broadness depends on which claim is asserted and what the accused product/method demonstrates.

Claim 1 / Claim 11: is the >3 ng/mL post-dose spike a hard limiter or a measurable metric?

• The claims specify a transient increase in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose.
• This is a measurable PK endpoint. The language reads as a binary compliance objective: the administration must be performed such that the patient’s measured transient increase does not exceed 3 ng/mL after a unit dose.

Practical scope consequence

• A competitor that chooses a different release strategy may still infringe if the resultant PK shows a transient spike >3 ng/mL.
• Conversely, a competitor could attempt to show that its regimen does not cause spikes above that threshold, but that is product- and protocol-specific.

Claim 9: does “sustained release over at least four hours” cover many extended-release formats?

• Claim 9 requires sustained release over at least four hours.
• This can be satisfied by many general “extended-release” approaches, depending on their dissolution/PK characterization.

Practical scope consequence

• Compared with the >3 ng/mL limiter, “≥4 hours” is a simpler structural/functional test.
• That makes claim 9 a potentially strong infringement basis for a broad class of extended-release tablets/capsules, even if their PK peak amplitude differs.

Claim 17: does the Cmax24hr/C24hr and Tmax language limit infringement to very specific PK shaping?

• Claim 17 requires a PK comparison to an equivalent amount immediate-release oral dosage:
  • (a) ratio of maximum serum concentration within 24 hours after administration to concentration at 24 hours (Cmax24hr/C24hr) is reduced vs immediate-release and/or
  • (b) Tmax is increased vs immediate-release.
• The claim also requires:
  • CKD sHPT treatment with reduced PTH
  • sustained release oral 25-hydroxyvitamin D3.

Practical scope consequence

• This claim is not merely “extended release.” It is PK-profile dependent and relative to immediate-release.
• A generic that matches dissolution timing but does not meet the specific relative Cmax/Tmax shaping may avoid claim 17, but could still fall under claims 1 or 9 depending on spike and release duration.

Which dependent claim features add formulation and carrier constraints (waxy carrier, lipoidic agent, oily vehicle)?

The formulation limitations appear in dependent claims and thus narrow the covered subject matter to specific construction features.

Claim 3 / Claim 12: waxy controlled release carrier

• Adds a carrier limitation to the sustained release oral 25-hydroxyvitamin D method claims.

Claim 4 / Claim 12: waxy carrier + lipoidic agent + oily vehicle

• Further specifies composition elements:
  • waxy controlled release carrier
  • lipoidic agent
  • oily vehicle

Scope consequence

• If a competitor avoids using a “waxy controlled release carrier” or avoids the listed composition combination, the dependent claims may be avoided.
• But note the independent claim set (1, 9, 17, 25) can still be asserted without those specific carrier elements, since those carrier limitations are not required in the independent claim recitations as provided.

What is the dosing scope: 30 µg vs 60 µg and once-daily administration?

The patent restricts meaningful portions of claim scope to:

• dose level: 30 µg or 60 µg
• frequency: once per day

Implications

• A product using other strengths (e.g., 20 µg, 40 µg) could be outside those dependent claims, but may still face risk under the independent claims if the independent claims do not require those dose limits (here, claim 1/9/17 as provided do not explicitly limit to 30/60 µg, while dependent claims do).
• Once-daily is repeated as a dependent narrowing constraint, but if the independent claim is broad enough (it appears to be, as given) the frequency may not be required for infringement under claims 1/9/17. Claim 25 explicitly requires once daily.

When does US 9,498,486 lose exclusivity: expiration timing for the US patent and any regulatory exclusivity overlay?

No filing date, patent term adjustment, or regulatory exclusivity (e.g., 5-year new chemical entity or 7-year orphan) is provided in the prompt. Without that, a correct expiration and exclusivity calendar cannot be produced.

How does US 9,498,486 compare to other calcifediol sHPT patent estates (generic entry risk)?

Given only the claim text, the landscape can be mapped by claim strategy type, not by competitor-specific patent numbers.

Common competitive pathways

1. A “same end-point, different formulation” approach
   • If a generic can avoid the >3 ng/mL spike and/or avoid the ≥4-hour sustained release characterization and/or avoid the relative PK shape metrics in claim 17, it can attempt to design around.
2. A “same PK, different route” approach
   • The claims are limited to oral sustained/extended release dosage forms.
   • Non-oral routes or non-extended release routes could reduce direct claim exposure (but would be competing for clinical efficacy and regulatory approval, separate issues).
3. A “different drug identity” approach
   • The claims are directed to 25-hydroxyvitamin D (and more specifically 25-hydroxyvitamin D3 in several claims). Substituting a different active (e.g., calcitriol or alfacalcidol) would generally avoid infringement, but changes the clinical mechanism and regulatory pathway.

Highest-risk infringement scenario

• A competitor launches an extended-release oral 25-hydroxyvitamin D3 product for CKD sHPT at 30/60 µg once daily, with measured PK consistent with the claimed spike-avoidance and/or extended-release behavior. That scenario aligns with claims 1, 9, 17, and likely 25.

What Orange Book status applies to US 9,498,486 and what does it imply for Paragraph IV filings?

No Orange Book listings, FDA application numbers, or Orange Book patent-expiry data are included in the prompt. A correct mapping from this specific patent to Orange Book “listed drug” coverage cannot be generated from the provided information.

What patent litigation affects US 9,498,486 and settlement risks for generics?

No litigation docket numbers, case captions, or settlement terms are provided. A factual litigation impact assessment cannot be produced from the prompt.

What regulatory status does US 9,498,486 cover for FDA approval pathway (505(b)(2) vs ANDA)?

No FDA submission details are provided. The claim text alone does not identify the drug product, NDA/ANDA/BLA, or reference listing necessary to connect the patent to a specific regulatory pathway.

Key freedom-to-operate (FTO) design-around levers embedded in the claim language

These levers are derived directly from claim limitations.

1) Avoid the “>3 ng/mL transient increase” objective (claim 1 / claim 11 / claim 19)

• If the competitor can document, across appropriate sampling and patient context, that no unit-dose administration produces transient increases above 3 ng/mL, it can attempt to avoid those claims.

2) Avoid “sustained release over at least four hours” (claim 9)

• If the accused product’s release characteristics do not meet the “at least four hours” requirement, claim 9 may be avoided.

3) Avoid the relative PK shaping required by claim 17

• Claim 17 needs either:
  • lower Cmax24hr/C24hr vs immediate-release, and/or
  • higher Tmax vs immediate-release.
• A design-around could aim for a PK profile that does not satisfy either sub-condition as required.

4) Avoid the dependent formulation carrier combination

• If a competitor avoids a “waxy controlled release carrier” and/or avoids the “waxy + lipoidic agent + oily vehicle” composition, it can target narrower dependent claims (but still must address independent claims that do not include those carrier constraints as provided).

5) Change dose strength and/or dosing regimen where claim elements require it

• Dependent claims lock to 30 µg or 60 µg and “once per day.”
• If a competitor uses different strengths and different dosing frequency, dependent-claim exposure reduces. The independent-claim exposure depends on whether independent claims require those constraints as provided (claim text provided indicates they are not universally required in claims 1/9/17, but claim 25 does require the niche dose/regimen).

Claim-by-claim scope map (based on the provided text)

Claim	Core method target	Dosage form	Key limiter(s) / PK objective	Dose / regimen	Patient CKD stage	Formulation/carrier constraints
1	Treat sHPT in CKD; reduce serum PTH	Sustained release oral 25-hydroxyvitamin D	Avoid transient 25(OH)D increase >3 ng/mL after unit dose	Not limited (unless dependent)	Not limited	Not required
2	Same as 1	Same	Same	30 µg or 60 µg	Not limited	Not required
3	Same as 1	Same	Same	Not limited	Not limited	Waxy controlled release carrier
4	Same as 1	Same	Same	Not limited	Not limited	Waxy carrier + lipoidic agent + oily vehicle
5	Same as 1	Same	Same	once per day	Not limited	Not required
6	Same as 1	Same	Same	Not limited	CKD Stage 5	Not required
7	Same as 1	Same	Same	Not limited	CKD Stage 1 or 2	Not required
8	Same as 1	Same	Same	Not limited	CKD Stage 3 or 4	Not required
9	Treat sHPT in CKD; reduce serum PTH	Sustained release oral 25-hydroxyvitamin D	Sustained release over ≥4 hours	Not limited (unless dependent)	Not limited	Not required
10	Same as 9	Same	Same	30 µg or 60 µg	Not limited	Not required
11	Same as 9	Same	Avoid transient >3 ng/mL	Not limited	Not limited	Not required
12	Same as 9	Same	Sustained release ≥4 hours + carrier	Not limited	Not limited	Waxy controlled release carrier
13	Same as 9	Same	Sustained release ≥4 hours + regimen	once per day	Not limited	Not required
14	Same as 9	Same	Sustained release ≥4 hours	Not limited	CKD Stage 5	Not required
15	Same as 9	Same	Sustained release ≥4 hours	Not limited	CKD Stage 1 or 2	Not required
16	Same as 9	Same	Sustained release ≥4 hours	Not limited	CKD Stage 3 or 4	Not required
17	Treat sHPT in CKD; reduce PTH	Sustained release oral 25(OH)D3	Lower Cmax24hr/C24hr vs immediate-release and/or increased Tmax vs immediate-release	Not limited	Not limited	Not required
18	Same as 17	Same	Same	30 µg or 60 µg	Not limited	Not required
19	Same as 17	Same	Avoid transient >3 ng/mL	Not limited	Not limited	Not required
20	Same as 17	Same	Same	Not limited	Not limited	Waxy controlled release carrier
21	Same as 17	Same	Same	once per day	Not limited	Not required
22	Same as 17	Same	Same	Not limited	CKD Stage 5	Not required
23	Same as 17	Same	Same	Not limited	CKD Stage 1 or 2	Not required
24	Same as 17	Same	Same	Not limited	CKD Stage 3 or 4	Not required
25	Treat sHPT; CKD stage specific niche; adult	Extended release oral 25(OH)D3	Not PK-limited here beyond extension	30 µg or 60 µg, once daily	Stage 3 or 4, with serum total 25(OH)D <30 ng/mL	Not required
26	Same as 25	Same	Same	Not limited	Not limited	Waxy controlled release carrier
27	Same as 25	Same	Same	Not limited	Not limited	Waxy carrier + lipoidic agent + oily vehicle
28	Same as 25	Same	Same	Not limited	CKD Stage 5 (note: depends on claim text; claim 25 says adult CKD stage 3 or 4, while dependent claim 28 asserts stage 5)	Not required
29	Same as 25	Same	Same	Not limited	CKD Stage 1 or 2	Not required
30	Same as 25	Same	Same	Not limited	CKD Stage 3 or 4	Not required

Potential internal inconsistency to flag in infringement mapping

The provided dependent claims include CKD Stage 5 as dependent of Claim 25, while Claim 25 limits CKD to Stage 3 or 4. If taken literally, that suggests Claim 25’s stage limitation is overridden/expanded by the dependent claim wording as written in the excerpt. That affects infringement analysis because a court may treat the dependency as requiring harmonization, but under literal reading it expands the covered population. This is a key point for claim construction and for mapping product use across CKD stages.

Key Takeaways

• US 9,498,486 is built around CKD sHPT treatment with extended/sustained-release oral 25-hydroxyvitamin D3 and a distinct PK theme: avoid a transient spike above 3 ng/mL and/or shift the PK profile vs immediate-release (dampen peak exposure and/or increase Tmax).
• The broadest infringement risks are formats that satisfy extended-release behavior (claim 9) and/or the spike limiter (claims 1/11/19). Carrier-specific elements (waxy/lipoid/oily) narrow only certain dependent claims.
• Design-around efforts should focus on PK compliance against the >3 ng/mL spike and on release/PK metrics rather than only on compositional changes.
• A full exclusivity, Orange Book, and litigation risk assessment cannot be completed from the prompt because it lacks the FDA listing, application link, and case records.

FAQs

1. Can a generic avoid infringement by using a different 25-hydroxyvitamin D form (e.g., calcifediol vs another vitamin D metabolite)?
2. Does meeting extended-release dissolution but failing the “>3 ng/mL” transient spike objective avoid claim 1?
3. How would a product demonstrate a “reduced Cmax24hr/C24hr” relative PK profile versus immediate-release for claim 17?
4. If a competitor changes dosing from once-daily to twice-daily, which claims remain most exposed?
5. How does CKD stage selection (Stage 1-2 vs 3-4 vs 5) change which claims are hardest to design around?

References (APA)

1. United States Patent 9,498,486.

Drugs Protected by US Patent 9,498,486

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Eirgen	RAYALDEE	calcifediol	CAPSULE, EXTENDED RELEASE;ORAL	208010-001	Jun 17, 2016		RX	Yes	Yes	9,498,486					USE OF SUSTAINED OR EXTENDED RELEASE ORAL 25-HYDROXYVITAMIN D3 IN TREATING SECONDARY HYPERPARATHROIDISM IN ADULT PATIENTS HAVING CHRONIC KIDNEY DISEASE STAGE 3 OR 4

International Family Members for US Patent 9,498,486

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2481400		301085	Netherlands
European Patent Office	2481400		122020000079	Germany
European Patent Office	2481400		CA 2020 00059	Denmark
European Patent Office	2481400		C02481400/01	Switzerland
European Patent Office	2481400		132021000000071	Italy
European Patent Office	2481400		C202130022	Spain
European Patent Office	2481400		CR 2020 00059	Denmark