United States Patent 9,943,530: Claim Scope, Rayaldee Patent Estate, and Generic Entry Risk

U.S. Patent No. 9,943,530 protects treatment methods using sustained-release 25-hydroxyvitamin D, particularly sustained-release calcifediol formulations administered at daily doses of 30 mcg to maintain serum 25-hydroxyvitamin D above 30 ng/mL. The claims cover both clinical outcomes and formulation characteristics, including wax-and-oil matrices, glycerides, soft capsules, release over at least four or eight hours, and reduced CYP24-mediated metabolism.

The patent is method-of-treatment focused. It does not broadly claim every composition containing calcifediol. A potentially infringing product must be used in a manner that satisfies the relevant dosing, formulation, release, patient-outcome, or comparative-performance limitations.

What patent protects sustained-release 25-hydroxyvitamin D?

U.S. Patent 9,943,530 is directed to methods for administering sustained-release 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or both. The claims cover:

Maintenance of serum 25-hydroxyvitamin D at 30 ng/mL or higher.
Once-daily administration.
Daily doses from 1 mcg to 100 mcg.
A specific 30 mcg daily dose of 25-hydroxyvitamin D3.
Treatment for at least three weeks.
Sustained release over at least four hours or at least eight hours.
Reduction of CYP24-mediated conversion to 24,25-dihydroxyvitamin D.
Lower risk of hypercalciuria, hypercalcemia, and hyperphosphatemia compared with immediate-release treatment.
Wax-and-oil matrix formulations.
Glyceride-containing lipid matrices.
Soft capsule dosage forms.

The commercial product most closely associated with this technology is Rayaldee, an extended-release calcifediol capsule marketed by OPKO Health for adults with secondary hyperparathyroidism and vitamin D insufficiency in chronic kidney disease. The FDA-approved Rayaldee dosage is 30 mcg orally once daily, with an increase to 60 mcg once daily in appropriate patients.[1]

How many patent claims does U.S. Patent 9,943,530 contain?

The supplied claim set contains 24 claims. Claim 1 and claim 14 are the principal independent claims. Claim 20 is also an independent method claim.

Claim group	Claims	Primary subject matter
Serum vitamin D maintenance	1-13, 21-24	Sustained-release 25-hydroxyvitamin D used to maintain serum levels
Metabolism management	14-19	Reduced CYP24-mediated catabolism and reduced metabolic surges
Intracellular hydroxylation	20	Reduced excessive intracellular 24-hydroxylation
Release duration	21-22	Release over at least four or eight hours
Matrix and dosage form	8-13, 19, 23-24	Wax, oil, glyceride, lipid matrix, and soft capsule limitations

Claims 2 through 13, 21, 22, 23, and 24 depend directly or indirectly from claim 1. Claims 15 through 19 depend from claim 14. This structure creates several narrower fallback positions, especially for a product using a 30 mcg soft capsule containing calcifediol in a wax-and-oil matrix.

What is the broadest claim in U.S. Patent 9,943,530?

Claim 1 is the broadest claim in the first claim family. It requires:

A patient.
Oral administration.
A sustained-release formulation.
25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination.
Maintenance of serum 25-hydroxyvitamin D at a level of at least 30 ng/mL.

Claim 1 does not require a particular dose, capsule shell, excipient, matrix, release duration, or 25-hydroxyvitamin D species. Those limitations appear in dependent claims.

The claim is broader than a claim limited to Rayaldee’s exact commercial formulation. A competing product could potentially fall within claim 1 even if it does not use the precise wax-and-oil matrix recited in claims 10, 13, 19, 23, and 24.

The principal vulnerability of claim 1 is its result limitation. Infringement analysis would likely focus on whether the accused regimen is shown or intended to maintain serum 25-hydroxyvitamin D at or above 30 ng/mL. A product label that recommends a regimen designed to achieve that outcome could create greater exposure than a label that merely describes calcifediol supplementation without a serum-level target.

What do claims 14 through 20 protect?

Claims 14 through 20 address pharmacokinetic and metabolic effects rather than only serum repletion.

Claim 14 requires a method of mitigating a surge in vitamin D metabolism by administering sustained-release 25-hydroxyvitamin D, with reduced CYP24-mediated catabolism compared with an equal dose of an immediate-release composition.

Claim 15 adds reduced risk of:

Hypercalciuria.
Hypercalcemia.
Hyperphosphatemia.

Claim 16 requires more efficient repletion of blood or intracellular 25-hydroxyvitamin D levels. Claim 17 requires avoidance of supraphysiologic concentrations in blood, cells, or the lumen.

Claim 20 is separately directed to reducing excessive intracellular 24-hydroxylation of 25-hydroxyvitamin D3 compared with an equal dose of an immediate-release composition.

These claims create evidentiary issues. They require comparison with an equal-dose immediate-release product or composition. A patent holder would generally need evidence showing the claimed metabolic or concentration difference. A generic applicant could challenge whether the claims are enabled across the full range of formulations and patient populations, and whether the claimed comparison is sufficiently definite.

What formulations are protected by Patent 9,943,530?

The formulation limitations are concentrated in claims 8 through 13 and 23 through 24.

Formulation limitation	Relevant claims	Scope
Matrix with a release-controlling constituent	8	Broad matrix limitation
Lipid matrix with a glyceride	9, 11	Requires glyceride-based lipid control
Wax and oil matrix	10, 13, 23, 24	Requires both wax and oil
Soft capsule	12, 13, 19, 24	Requires soft capsule dosage form
Wax-and-oil matrix inside soft capsule	13, 19, 24	Narrowest commercial-style formulation
1-50 mcg active amount	6, 7, 23, 24	Narrows dose per formulation
Release for at least four hours	21	Release-duration limitation
Release for at least eight hours	22	More restrictive duration limitation

Claims 13 and 24 are particularly relevant to a Rayaldee-like product because they combine calcifediol, a wax-and-oil matrix, and a soft capsule shell. A formulation using a tablet, osmotic system, polymeric bead, or non-lipid extended-release platform may avoid those narrower claims while remaining potentially exposed under claim 1 or claim 14.

The patent does not require every formulation claim to use 30 mcg. Claims 13, 19, 21, and 22 do not independently impose that specific dose, although their dependency structure may incorporate limitations from parent claims.

When does U.S. Patent 9,943,530 expire?

The patent issued on March 13, 2018. Its underlying priority chain is associated with the sustained-release vitamin D technology developed for calcifediol products. The nominal patent term is expected to run to approximately December 2030, subject to any applicable patent-term adjustment, terminal disclaimer, or other term calculation shown in the USPTO record.[2]

The patent term should not be confused with FDA regulatory exclusivity. Patent expiration and FDA exclusivity operate independently:

Protection type	Relevance
Patent term	Blocks or creates infringement risk for covered commercial conduct
New-drug exclusivity	Restricts certain FDA approval actions for a defined period
Orphan-drug exclusivity	Can block approval of the same drug for the same orphan indication
Pediatric exclusivity	Can add six months to qualifying protections
Patent listing	Determines whether an ANDA applicant must address the patent through Paragraph IV or a statement under 21 U.S.C. § 505(j)

A definitive launch date requires review of the current USPTO term calculation, Orange Book listing, regulatory exclusivity, litigation history, and any settlement agreement.

What is the Orange Book status of the patent?

Rayaldee is an FDA-approved extended-release calcifediol product. The FDA Orange Book identifies patents and use codes associated with approved products when the sponsor submits qualifying patent information under the Hatch-Waxman framework.[3]

For generic applicants, the central questions are:

Whether U.S. Patent 9,943,530 is listed for Rayaldee.
Which claims or approved methods are mapped to the listed use code.
Whether the proposed ANDA label includes the patented use.
Whether the applicant files a Paragraph IV certification.
Whether the patent holder files an infringement action within 45 days.

A listed method-of-use patent does not automatically block every generic version. An ANDA applicant may pursue a section viii statement if it can carve out the patented method from the proposed labeling and still obtain approval. That strategy is more difficult where the approved label inherently instructs the patented dose, sustained-release administration, or treatment objective.

What Paragraph IV challenges are possible?

A generic calcifediol applicant could use several challenge routes:

Invalidity challenge

Potential grounds could include lack of written description, lack of enablement, obviousness, indefiniteness, or patentable subject-matter issues. The strongest obviousness theory would likely combine prior art on:

Immediate-release calcifediol.
Extended-release vitamin D preparations.
Lipid and wax matrix delivery systems.
Serum vitamin D targets.
CYP24-mediated vitamin D metabolism.
Once-daily dosing.

The patent holder would counter that the claimed release profile reduces supraphysiologic exposure and CYP24-mediated catabolism in a way not predictable from the prior art.

Noninfringement challenge

A generic applicant may design around the narrower limitations by using:

A non-wax release-control system.
A non-oil matrix.
A hard capsule or tablet.
An immediate-release dosage form.
A formulation with a different release profile.
A label that does not direct maintenance of serum 25-hydroxyvitamin D at 30 ng/mL or higher.

The principal risk is claim 1, which does not require the specific wax-and-oil matrix or soft capsule. A formulation design-around may therefore avoid claims 13, 19, and 24 without avoiding the broadest method claim.

Section viii carve-out

A section viii strategy could remove patented method language from the label. Its viability depends on whether the remaining label still recommends the same sustained-release calcifediol use. FDA and court analysis generally focuses on the totality of the labeling and the practical uses encouraged by the proposed product.

Which companies are challenging the Rayaldee patent estate?

The patent landscape should distinguish publicly disclosed litigation from potential ANDA activity. An ANDA Paragraph IV filing may remain confidential until the patent holder files suit or the applicant makes a public disclosure. The existence of U.S. Patent 9,943,530 alone does not establish that a particular generic company has challenged it.

The relevant competitive groups are:

Competitor type	Likely pathway	Main exposure
Generic calcifediol manufacturer	ANDA	Patent validity, infringement, label carve-out
Alternative vitamin D developer	NDA or 505(b)(2)	Different formulation or dosing strategy
Compounded pharmacy	State and federal compounding rules	Product-specific patent and regulatory risk
Biosimilar developer	Not applicable	Calcifediol is a small molecule, not a biologic
Supplement manufacturer	Dietary supplement pathway	May avoid prescription-drug claims but cannot rely on the same regulatory pathway

There is no biosimilar pathway for calcifediol. Competitive entry would occur through an ANDA, a 505(b)(2) application, an independent NDA, or a non-prescription product route.

How strong is the patent estate for Rayaldee?

The estate is strongest against a product that replicates all of the following:

Extended-release calcifediol.
Oral once-daily administration.
A 30 mcg or comparable daily dose.
A wax-and-oil or glyceride-containing matrix.
A soft capsule.
A label directed to vitamin D repletion or maintenance.
A pharmacokinetic profile designed to avoid high post-dose concentrations.

The estate is weaker against an immediate-release product, a non-lipid delivery system, or a product whose label avoids the claimed serum maintenance and metabolic objectives. The broad method claims nevertheless create residual risk because they are not limited to a particular excipient system.

Claim strength is mixed:

Claim category	Relative strength
Broad serum-maintenance method	Commercially important but exposed to result-limitation and prior-art arguments
30 mcg once-daily regimen	Stronger commercial relevance; narrower scope
Wax-and-oil soft capsule	Stronger structural specificity; easier to design around
CYP24 reduction claims	Potentially valuable but dependent on comparative evidence
At-least-four/eight-hour release claims	Useful for distinguishing immediate release; dependent on testing and construction

What generic launch scenarios exist?

Scenario 1: No Paragraph IV challenge

A generic entrant waits for patent expiry or relies on a noninfringing formulation. This is the lowest litigation-risk path but delays entry.

Scenario 2: Paragraph IV with litigation

The applicant certifies that the patent is invalid, unenforceable, or not infringed. A timely infringement suit can trigger the statutory 30-month stay under the Hatch-Waxman framework, subject to court and regulatory developments.[4]

Scenario 3: Section viii carve-out

The applicant removes the patented method from its label. Approval depends on whether the remaining label still supports an unpatented use.

Scenario 4: 505(b)(2) alternative

A sponsor develops a different sustained-release platform, dose, or indication. This may avoid some formulation claims but can still face method-of-use or clinical bridging issues.

Scenario 5: At-risk launch

The applicant launches before final resolution after receiving approval or after the statutory stay ends. This creates potential damages, injunction, and enhanced-risk exposure if infringement is later established.

What patent litigation and settlements affect entry?

A complete litigation assessment requires the current PACER docket, USPTO assignment and term records, FDA Orange Book updates, and publicly available ANDA notices. The supplied claims alone do not establish a pending case, settlement, covenant not to sue, license, or authorized generic arrangement.

Any settlement affecting commercial entry would require analysis of:

Entry date.
Patent-by-patent release.
Authorized generic rights.
Supply or licensing obligations.
Acceleration clauses.
Treatment of future patent grants.
FTC review under the Medicare Modernization Act disclosure framework.

No conclusion about a particular generic company or settlement should be drawn solely from the patent claims.

What licensing deals are relevant?

The technology is associated with the calcifediol development program that led to Rayaldee. Commercial rights, development agreements, and corporate transactions involving OPKO Health and predecessor entities may affect ownership, enforcement, or royalty economics. Patent ownership should be checked through the USPTO assignment history rather than inferred from the product label or the named marketing company.

A licensee may have standing to enforce the patent only if the agreement transfers sufficient exclusionary rights. A nonexclusive licensee generally cannot sue alone for infringement. This issue can affect litigation strategy, settlement authority, and damages allocation.

What is the revenue exposure from generic entry?

Rayaldee revenue exposure depends on product sales, payer coverage, chronic kidney disease prescribing, pricing, and the timing of competing entry. A generic launch would likely affect:

Net price.
Formulary positioning.
Specialty pharmacy distribution.
Prescriber switching.
Reimbursement for extended-release calcifediol.
Market share retained by the branded product.

The patent claims protect a commercially specific product profile, but they do not create a complete barrier to every vitamin D product. The largest exposure comes from a generic that matches the extended-release calcifediol dosage form and labeled treatment objective. A noninfringing immediate-release or alternative controlled-release product could compete without necessarily practicing every asserted claim.

Key Takeaways

U.S. Patent 9,943,530 primarily protects methods using sustained-release calcifediol.
Claim 1 is the broadest serum-maintenance claim and does not require a wax-and-oil matrix or soft capsule.
Claims 13, 19, and 24 provide narrower protection for calcifediol in a wax-and-oil matrix within a soft capsule.
Claims 14 through 20 target reduced CYP24-mediated metabolism and intracellular 24-hydroxylation compared with immediate-release treatment.
The patent is expected to have a nominal term extending to approximately December 2030, subject to the official USPTO term calculation.
Calcifediol is a small molecule, so biosimilar litigation is not relevant.
Generic entry would most likely proceed through an ANDA, Paragraph IV certification, section viii carve-out, or a formulation design-around.
The principal commercial risk is a generic extended-release calcifediol product that matches the 30 mcg once-daily regimen and the claimed pharmacokinetic profile.
A current Orange Book, litigation, assignment, and settlement review is required before making a definitive launch or freedom-to-operate determination.

FAQs

Does Patent 9,943,530 cover immediate-release calcifediol?

No. The claims require a sustained-release formulation or sustained-release dosage form. An immediate-release product would generally avoid the sustained-release limitation, although other patents or regulatory protections could apply.

Does the patent require Rayaldee by name?

No. The claims are written around active ingredient, dosage, release characteristics, formulation structure, and treatment outcomes. They do not require the trademark Rayaldee.

Can a tablet avoid the patent?

A tablet may avoid claims requiring a soft capsule, wax-and-oil matrix, or both. It could still face claims that require only an oral sustained-release formulation and the claimed serum-level or metabolic outcome.

Is 30 mcg the only protected dose?

No. The claims cover broader ranges, including 1 to 100 mcg per day and 1 to 50 mcg in specified formulations. The 30 mcg limitation is a narrower claim feature with direct commercial relevance.

Does FDA approval prove patent infringement?

No. FDA approval and patent infringement are separate issues. Approval may proceed after a Paragraph IV certification, a section viii statement, patent expiry, settlement, or resolution of litigation. Infringement depends on whether the approved product and its labeled use practice the asserted claims.

References

U.S. Food and Drug Administration. (2016). Rayaldee (calcifediol) extended-release capsules: Prescribing information. FDA.
United States Patent and Trademark Office. (2018). U.S. Patent No. 9,943,530, methods of treating vitamin D insufficiency and related sustained-release calcifediol methods. USPTO.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.
21 U.S.C. § 355(j) (2023).

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	⤷ Start Trial	⤷ Start Trial				MAINTAINING SERUM 25-HYDROXYVITAMIN D AT A LEVEL OF AT LEAST 30 NG/ML WITH ORAL, SUSTAINED RELEASE 25-HYDROXYVITAMIN D	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2640094	⤷ Start Trial
Canada	2882048	⤷ Start Trial
Cyprus	1118017	⤷ Start Trial
Denmark	1993559	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,943,530

Which drugs does patent 9,943,530 protect, and when does it expire?

Summary for Patent: 9,943,530