United States Patent 4,341,774: Scope, Claims, Expiration, and Patent Landscape for Vitamin D Immunosuppression

United States Patent 4,341,774 covers the medical use of cholecalciferol, vitamin D derivatives, or both to suppress abnormal immune activity in humans. The claims reach autoimmune disease treatment and suppression of graft rejection, with dependent claims specifying daily dosage and blood-concentration ranges. The patent issued in 1982 and, under the pre-Uruguay Round patent-term regime, expired no later than 17 years after issuance. It therefore has no current exclusionary value, no viable Paragraph IV position, and no biosimilar relevance.

What does US Patent 4,341,774 protect?

The patent protects a method of treating a human who requires immunosuppression by administering cholecalciferol or a derivative in an amount sufficient to suppress an abnormal rise in immunological function.

The claim structure is:

Claim	Subject matter	Limitation
1	Core immunosuppression method	Cholecalciferol and/or derivative administered to a human in need of immunosuppression
2	Daily dose	0.25 to 10 micrograms per adult per day
3	Narrower daily dose	0.5 to 5 micrograms per adult per day
4	Blood concentration	0.01 to 1 microgram/mL of active ingredient
5	Disease-specific use	Treatment of a human with an autoimmune disease
6	Specific autoimmune diseases	Chronic thyroiditis, autoimmune hemolytic rheumatoid arthritis, or systemic lupus erythematosus
7	Transplantation use	Suppression of graft rejection

The patent is a method-of-treatment patent. It does not claim:

A new vitamin D compound;
A pharmaceutical composition;
A tablet, capsule, injectable, or other dosage form;
A manufacturing process;
A formulation containing vitamin D;
A specific transplant protocol;
A specific combination with another immunosuppressant.

The patent's commercial scope therefore depended on use of a claimed vitamin D substance for the claimed immunosuppressive purpose, rather than on ownership of the active ingredient itself.

How broad is claim 1 of US 4,341,774?

Claim 1 is the broadest claim and contains four principal elements:

A method;
Treatment of a human;
A human in need of immunosuppression;
Administration of cholecalciferol and/or a derivative in an amount sufficient to suppress an abnormal rise in immunological function.

The phrase "cholecalciferol and/or its derivative" is materially broad. It can be read to cover administration of vitamin D3 alone, a vitamin D derivative alone, or both together. The claim does not identify a particular derivative by chemical name or structural formula.

That breadth creates two opposing effects:

It potentially covers numerous vitamin D analogues and therapeutic implementations.
It creates vulnerability over written description, enablement, definiteness, anticipation, and obviousness if the specification does not adequately support the full universe of derivatives.

The claim also uses a functional endpoint: suppression of an "abnormal rise in immunological function." Functional language can extend claim coverage beyond a defined disease label, but enforcement would require proof that the accused administration was directed to immunosuppression and achieved, or was intended to achieve, the claimed biological result.

What do claims 2 through 4 add?

What dosage range is protected?

Claim 2 narrows claim 1 to 0.25 to 10 micrograms per adult per day. Claim 3 further limits the dose to 0.5 to 5 micrograms per adult per day.

These claims are narrower than claim 1 but may have been commercially important because they distinguish immunosuppressive use from ordinary nutritional supplementation. The claimed amounts are low compared with doses that can produce vitamin D toxicity, although the legal relevance of that distinction depends on the patent specification and the prior art.

A product or treatment protocol outside the claimed daily ranges would not infringe claims 2 or 3, but it could still implicate claim 1 if the other elements were met.

What blood concentration is required by claim 4?

Claim 4 requires administration that produces an active-ingredient blood concentration of 0.01 to 1 microgram/mL.

This is a result-based limitation. In an infringement analysis, the relevant issue would be whether administration produced the specified concentration, not simply whether the label recommended a particular dose. The claim raises several technical questions:

Which vitamin D compound is measured?
Is the concentration total circulating compound or free compound?
Is the measurement taken at steady state, peak concentration, or trough concentration?
Does the range apply to cholecalciferol, a metabolite, or an administered derivative?
What analytical method was contemplated by the patent?

Those issues could make claim 4 difficult to enforce without reliable pharmacokinetic evidence.

Which diseases are covered by US 4,341,774?

Claim 5 covers autoimmune disease generally, subject to the limitations of claim 1.

Claim 6 identifies:

Chronic thyroiditis;
Autoimmune hemolytic rheumatoid arthritis, as stated in the supplied claim text;
Systemic lupus erythematosus.

The wording "autoimmune hemolytic rheumatoid arthritis" appears unusual from a modern medical-classification perspective. It should be treated as the text of the issued claim unless the official patent document shows a different transcription, correction, or punctuation.

Claim 7 covers suppression of graft rejection. This provides a separate transplant-related use category and is not limited to a named organ in the claim text. The claim could potentially encompass kidney, liver, heart, lung, or other graft-rejection settings, subject to the scope of claim 1 and the patent's disclosure.

When did US Patent 4,341,774 lose exclusivity?

US Patent 4,341,774 issued in 1982. For a United States utility patent filed before June 8, 1995, the ordinary term was 17 years from issuance, subject to applicable prosecution-delay adjustments and other historical rules. The patent therefore expired in approximately 1999, absent an unusual term adjustment or extension.

Event	Timing
US patent issued	1982
Governing term regime	17 years from grant for pre-June 8, 1995 patents
Approximate ordinary expiration	1999
Current enforceability	None based on ordinary patent term

The patent cannot create present-day exclusivity for vitamin D immunosuppressive use. Patent term restoration under the Hatch-Waxman framework would not ordinarily revive a patent of this age into the current period, and no current patent-term extension is indicated by the claim set.

What is the Orange Book status of US Patent 4,341,774?

US Patent 4,341,774 is not a current Orange Book barrier.

The Orange Book lists patents submitted for approved prescription drug products, primarily under the Hatch-Waxman framework. A decades-old method patent covering a broad vitamin D immunosuppression concept does not itself establish an Orange Book-listed barrier for current vitamin D products. Any historical listing would have expired with the patent and would not block approval of a competing product today. FDA, Approved Drug Products with Therapeutic Equivalence Evaluations.

The patent also does not claim a specific approved product, dosage form, or formulation. Its relevance is therefore distinct from an Orange Book composition or formulation patent.

Are there Paragraph IV challenges to US 4,341,774?

No current Paragraph IV challenge has practical significance because the patent expired approximately two decades ago.

A Paragraph IV certification is used when an abbreviated new drug application applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. That mechanism is relevant during the enforceable life of an Orange Book-listed patent. An expired patent cannot support a current Hatch-Waxman 30-month stay or a new period of statutory exclusivity.

Potential historical ANDA activity involving vitamin D products would not change the present status of US Patent 4,341,774. Vitamin D products may also proceed through pathways that do not depend on this patent, including OTC drug regulation where applicable.

What formulations are protected by US 4,341,774?

None are claimed expressly.

The patent claims a therapeutic administration method, not a formulation. It does not require or exclude:

Oral tablets;
Soft gelatin capsules;
Liquid formulations;
Injectable products;
Lipid-based formulations;
Controlled-release systems;
Combination products;
Nanoparticle or microsphere delivery systems.

A later formulation patent could have created separate protection for a particular vitamin D dosage form, excipient system, particle size, stability profile, or delivery technology. Such a later patent would need to be analyzed independently. US 4,341,774 does not provide formulation protection by itself.

Does US 4,341,774 create biosimilar risk?

No. Biosimilar regulation applies to biological products, while cholecalciferol and conventional vitamin D derivatives are small molecules or chemical entities. The patent therefore has no biosimilar barrier function.

For a vitamin D analogue that is a new chemical entity, relevant competition would generally involve small-molecule generic, hybrid, or other drug-approval pathways rather than a 351(k) biosimilar pathway.

How strong is the patent estate?

The current patent estate is commercially inactive because the patent has expired. Historically, the issued claims had moderate conceptual breadth but limited product-control power.

Strength factor	Assessment
Active ingredient coverage	Broad wording for cholecalciferol and derivatives
Disease coverage	Broad autoimmune-disease language, with named diseases in claim 6
Transplant coverage	Broad graft-rejection use in claim 7
Dose coverage	Defined ranges in claims 2 and 3
Pharmacokinetic coverage	Blood concentration range in claim 4
Composition protection	None
Formulation protection	None
Manufacturing protection	None
Current term	Expired
Current enforcement value	None

The absence of composition and formulation claims would have allowed competitors to design around the patent through product architecture, assuming they avoided the claimed immunosuppressive use. A competitor could also have pursued non-immunosuppressive indications or supplied vitamin D for nutritional or replacement purposes, although intended use and labeling would remain relevant in a historical infringement analysis.

What patent landscape surrounds vitamin D immunosuppression?

The broader landscape divides into four technology groups.

Vitamin D compounds and analogues

This category includes patents claiming specific chemical derivatives, stereoisomers, hydroxylation patterns, prodrugs, and metabolites. Such patents can be stronger than US 4,341,774 because they control the molecule itself rather than only one therapeutic use.

Immunomodulatory methods

Later patents may claim vitamin D analogues for autoimmune disorders, inflammatory disease, transplant tolerance, psoriasis, multiple sclerosis, inflammatory bowel disease, or other immune-mediated conditions. These claims may overlap conceptually with the 4,341,774 claims but can remain independently enforceable if their patent terms are still active.

Formulation and delivery systems

Separate patents may cover oral, injectable, topical, depot, liposomal, or controlled-release preparations. These rights can create commercial barriers even when the underlying vitamin D molecule is old.

Combination therapies

Combination patents may claim vitamin D analogues administered with calcineurin inhibitors, corticosteroids, antiproliferative agents, biologics, or other immunosuppressants. They may be relevant to graft rejection and autoimmune disease protocols.

Because US 4,341,774 expired, freedom-to-operate analysis today should focus on later patents covering the selected vitamin D derivative, formulation, indication, dosing regimen, and combination therapy.

Which companies are challenging US 4,341,774?

No current challenger has a meaningful legal position against the patent because the patent is expired. The relevant competitive question is not who is challenging the patent, but which companies hold later, unexpired rights covering vitamin D analogues or immune-modulating uses.

Generic manufacturers can generally enter without overcoming this patent. Their remaining risks would arise from later patents, regulatory exclusivity, product-specific labeling, or market authorization requirements.

What litigation and settlement issues affect the patent?

An expired patent cannot support a new injunction, ongoing royalty obligation, or exclusionary settlement concerning future conduct. Any historical litigation or settlement would need to be assessed against the patent's expiration date and the specific parties involved.

The claims could historically have generated disputes over:

Whether a derivative fell within "cholecalciferol and/or its derivative";
Whether the defendant's product was administered for immunosuppression;
Whether autoimmune or graft-rejection treatment was intended;
Whether the dose or blood concentration fell within claims 2 through 4;
Whether the patent was enabled across the full derivative class;
Whether prior art disclosed vitamin D's immunomodulatory effects.

Those issues no longer create a current patent-exclusion risk under US 4,341,774 itself.

What generic launch scenarios exist?

For a current product, three launch scenarios are most relevant:

An ordinary generic vitamin D product can launch without waiting for this patent.
A vitamin D derivative product must clear later compound, formulation, method-of-use, and regulatory barriers.
A product labeled for autoimmune disease or graft-rejection treatment must be screened against later indication and dosing patents, even though US 4,341,774 is expired.

A skinny-label strategy could be relevant where later patents cover only particular immunosuppressive uses. That analysis depends on the later patent landscape and the approved labeling, not on the expired 4,341,774 claims.

Key Takeaways

US Patent 4,341,774 claims human immunosuppression using cholecalciferol or a vitamin D derivative.
The broadest claim covers administration for abnormal immune activation.
Dependent claims specify 0.25 to 10 micrograms per day, 0.5 to 5 micrograms per day, and a blood concentration of 0.01 to 1 microgram/mL.
The patent expressly reaches autoimmune disease and graft-rejection suppression.
It claims methods only, not vitamin D compounds, formulations, manufacturing methods, or dosage forms.
The patent issued in 1982 and expired approximately in 1999 under the historical 17-year-from-grant term.
It has no current Orange Book, Paragraph IV, biosimilar, litigation, or settlement significance.
Current freedom-to-operate risk depends on later patents covering specific vitamin D analogues, formulations, combinations, dosing regimens, and indications.

FAQs

Can an expired method patent block a new vitamin D immunosuppressant?

No. An expired patent cannot support a current infringement injunction or prevent commercial entry. Later patents may still cover the specific derivative, formulation, or indication.

Does claim 1 cover ordinary vitamin D supplementation?

Not necessarily. Claim 1 requires administration to a human in need of immunosuppression and an amount sufficient to suppress abnormal immune activity. Nutritional supplementation without the claimed therapeutic purpose would not automatically satisfy those limitations.

Does US 4,341,774 claim calcitriol?

The supplied claims do not name calcitriol. They use the broader phrase "cholecalciferol and/or its derivative." Whether a particular compound falls within that phrase would depend on claim construction and the patent disclosure.

Can a later patent have longer protection than US 4,341,774?

Yes. A later patent may remain active if it claims a specific vitamin D analogue, formulation, dosing regimen, combination, or therapeutic indication that was not claimed or disclosed in the earlier patent.

Is graft rejection treatment the same as autoimmune disease treatment under the claims?

No. Claim 7 separately addresses suppression of graft rejection. Claims 5 and 6 address autoimmune disease. The two use categories should be analyzed independently when reviewing infringement or later patent overlap.

References

U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

U.S. Patent No. 4,341,774. (1982). Method for immunosuppression using cholecalciferol or a derivative. United States Patent and Trademark Office.

United States Code, 35 U.S.C. § 154. (2024). Patent term.

United States Code, 21 U.S.C. § 355. (2024). New drug applications and abbreviated applications.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	54-101211	Aug 10, 1979

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Japan	S5626820	⤷ Start Trial
Japan	S6365646	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,341,774

Summary for Patent: 4,341,774