United States Patent 6,399,101: Scope, Claims, Expiration, and Levothyroxine Patent Landscape

U.S. Patent No. 6,399,101 covers stabilized solid pharmaceutical preparations containing levothyroxine sodium or another thyroid hormone in combination with silicified microcrystalline cellulose, together with specified tablet excipients and manufacturing steps. The patent’s relevant 20-year term has expired. It therefore does not create a current U.S. patent barrier to generic levothyroxine products, although it remains relevant to historical formulation strategy, prior-art analysis, and freedom-to-operate reviews covering earlier commercial periods.

What does U.S. Patent 6,399,101 cover?

The patent covers two principal subject-matter groups:

Pharmaceutical compositions containing a thyroid hormone and silicified microcrystalline cellulose, or SMCC.
A manufacturing process that creates separate active and color blends before adding a disintegrant and lubricant and compressing the blend into tablets.

The central technical concept is the use of SMCC as a stabilizing matrix for thyroid-hormone particles. The claims are directed primarily to solid oral tablets, although several composition claims are not expressly limited to tablets.

The patent does not claim levothyroxine sodium as a chemical compound. It claims a formulation architecture and a manufacturing process.

Core patent data

Field	Data
Patent	U.S. Patent No. 6,399,101
Title	Stabilized pharmaceutical preparations containing thyroid hormones
Technology	Levothyroxine and thyroid-hormone solid formulations
Principal excipient	Silicified microcrystalline cellulose
Key dosage form	Tablet
Grant date	June 4, 2002
Earliest priority date	October 15, 1998
Patent-term endpoint	October 15, 2019, subject to any applicable term adjustment or disclaimer
Current enforceability	Expired
Patent type	Small-molecule formulation and manufacturing patent
Biosimilar relevance	None; levothyroxine is a synthetic small molecule, not a biologic

The priority and term information should be read against the official patent file and USPTO term records. The patent’s expiration means that the claims no longer provide enforceable exclusionary rights in the United States. [1][2]

How broad are the independent claims?

Claims 1, 5, 11, and 12 are the principal scope-defining claims. Claims 2 through 4, 6 through 10, and 13 through 15 add narrower limitations.

Claim 1: Levothyroxine sodium plus SMCC

Claim 1 requires:

a stabilized pharmaceutical preparation;
a therapeutically effective amount of levothyroxine sodium; and
silicified microcrystalline cellulose.

The claim does not require a disintegrant, lubricant, coloring agent, or tablet. A formulation containing levothyroxine sodium and SMCC could fall within the literal wording even if it uses a different tablet architecture, provided the preparation is considered stabilized.

The principal interpretation issue is the term “stabilized.” The claim does not define stabilization solely by a numerical impurity limit in the language supplied. In a historical infringement dispute, the specification, examples, analytical data, and prosecution history would be important in determining whether the term imposes a measurable stability requirement.

Claim 5: SMCC stabilizing matrix

Claim 5 narrows the technical structure. It requires:

a stabilizing matrix;
the matrix to consist essentially of SMCC;
a therapeutically effective amount of levothyroxine sodium particles; and
the particles to be captured and protected within the matrix.

“Consisting essentially of” generally permits additional ingredients that do not materially alter the basic and novel characteristics of the claimed formulation. The basic characteristic appears to be stabilization of thyroid-hormone particles through their incorporation into an SMCC matrix.

Claim 5 is narrower than claim 1 because it adds a particle-capture and matrix-protection concept. A product using SMCC merely as a conventional diluent might present a stronger non-infringement position than a product in which levothyroxine particles are deliberately embedded or captured within an SMCC matrix.

Claim 11: Thyroid hormones beyond levothyroxine

Claim 11 substitutes “a thyroid hormone” for levothyroxine sodium. On its face, this extends the composition scope to other thyroid hormones, subject to the patent’s specification and claim-construction rules.

Potentially relevant substances include:

levothyroxine sodium, or T4;
liothyronine sodium, or T3;
combinations of T4 and T3;
desiccated thyroid-derived hormone preparations, depending on how “thyroid hormone” is construed.

Claim 11 is commercially broader than claims 1 and 5 because it is not limited to levothyroxine sodium. It still requires SMCC and a stabilized pharmaceutical preparation.

Claim 12: Manufacturing process

Claim 12 covers a specific tablet-manufacturing sequence:

Blend SMCC with one or more thyroid hormones to form an active blend.
Blend dye or dyes with SMCC to form a color blend.
Combine the active blend, color blend, and disintegrant into a preblend.
Add lubricant to create a final blend.
Compress the final blend into a tablet.

The claim is not a generic wet-granulation or direct-compression claim. It requires the separate active and color blends and the stated order of operations.

A manufacturer could potentially avoid literal infringement by omitting one required step, combining the colorant directly into the active blend, using a different process sequence, or producing a dosage form other than a compressed tablet. Whether such alternatives would raise a doctrine-of-equivalents issue would depend on the facts and the historical enforceability period.

What formulations are protected by the dependent claims?

The dependent claims identify excipient combinations that narrow the broad composition claims.

Claim	Limitation
2	Adds a disintegrant and lubricant
3	Disintegrant is sodium starch glycolate
4	Lubricant is magnesium stearate
6	Adds a disintegrant, lubricant, and coloring agent
7	Disintegrant is sodium starch glycolate, pregelatinized starch, or cellulose
8	Lubricant is magnesium stearate, calcium stearate, talc, or stearic acid
9	Disintegrant is sodium starch glycolate and lubricant is magnesium stearate
10	Preparation is a tablet
13	Thyroid hormone in the process is levothyroxine sodium
14	Process disintegrant is sodium starch glycolate
15	Process lubricant is magnesium stearate

Claim 9 is the most commercially specific composition claim in the supplied set. It combines:

SMCC;
levothyroxine sodium particles;
sodium starch glycolate; and
magnesium stearate.

Claim 15 is the corresponding narrow process limitation for levothyroxine sodium, sodium starch glycolate, and magnesium stearate.

The use of a different lubricant or disintegrant would avoid the literal limitations of claims 3, 4, 9, 14, and 15, but would not necessarily avoid claims 1, 5, 11, or 12.

How does claim scope differ between composition and process claims?

Composition claims generally present the greater risk during the patent term because they attach to the finished product. A product can infringe regardless of how it was manufactured.

Process claim 12 requires proof that the accused manufacturer performed each recited manufacturing step. This can make process enforcement more fact-intensive. Discovery into batch records, master production records, validation protocols, and manufacturing instructions would typically be necessary.

The distinction is material:

Issue	Composition claims	Process claim
Primary target	Finished formulation	Manufacturing method
Proof focus	Ingredients, structure, and stabilization	Manufacturing records and process sequence
Design-around route	Remove SMCC or alter matrix architecture	Change blending order or eliminate separate color blend
Claims implicated	1, 5, 11 and dependents	12 and dependents
Current enforceability	Expired	Expired

When did U.S. Patent 6,399,101 lose exclusivity?

The patent’s relevant term ended on October 15, 2019, based on the earliest claimed priority date and the standard 20-year patent term framework. The patent was granted in 2002, but the grant date does not control the expiration date for a post-1995 U.S. utility patent.

The practical timeline is:

Event	Date
Earliest priority	October 15, 1998
Grant	June 4, 2002
Expected standard expiration	October 15, 2019
Current status	Expired

No current Paragraph IV certification can create a litigation risk based solely on this patent. A Paragraph IV certification is relevant only while an asserted patent is unexpired and listed or otherwise used as a patent basis under the applicable ANDA framework. A historical ANDA challenge could have addressed the patent before expiration, but the supplied information does not establish a specific challenger or litigation outcome.

What is the Orange Book status of U.S. Patent 6,399,101?

Patent status and Orange Book status are separate questions.

A patent may be:

issued but never listed in the Orange Book;
listed against one NDA but not another;
listed for a particular dosage form or strength;
removed, expired, or retained as an historical listing.

The existence of U.S. Patent 6,399,101 does not establish that it was listed against Synthroid, Levoxyl, Unithroid, Levothroid, or another levothyroxine product. Orange Book listings are tied to specific approved products and NDA holders, not to the active ingredient in the abstract. The current regulatory significance of this patent is therefore zero as an enforceable barrier, irrespective of any historical listing.

FDA’s Orange Book remains the controlling source for product-specific patent and exclusivity information. [3]

Which products and companies were commercially relevant?

The U.S. levothyroxine market has included branded and generic products such as:

Synthroid;
Levoxyl;
Unithroid;
Levothroid;
generic levothyroxine sodium tablets.

Relevant commercial participants have included AbbVie, King Pharmaceuticals, Jerome Stevens Pharmaceuticals, Lannett, Mylan or Viatris, Sandoz, and other ANDA sponsors over different periods. Ownership and marketing arrangements have changed over time, so a company associated with a brand or ANDA at launch may not be the current rights holder or marketer.

The patent itself does not establish that any particular brand used the claimed formulation. Product-label review, regulatory filings, development records, and technical comparisons are required to link a marketed product to the claimed SMCC matrix.

Which companies challenged the patent under Paragraph IV?

The supplied claim text does not identify any Paragraph IV challenger, ANDA sponsor, case number, settlement, or court decision. No challenger or settlement should be attributed to this patent without a verified FDA, PACER, district-court, or Federal Circuit record.

Because the patent expired in 2019, any historical Paragraph IV event would now be relevant mainly to launch timing, damages, and settlement analysis. It would not create a present generic-entry restriction.

How strong was the patent estate?

Technical strength

The patent had a focused formulation concept rather than broad chemical coverage. Its strongest technical position was the combination of:

levothyroxine sodium;
SMCC;
particle capture within an SMCC matrix;
defined tablet excipients; and
a separate active-blend and color-blend process.

Its scope was more limited than a patent claiming all stabilized levothyroxine formulations or all tablet formulations containing a stabilizer.

Design-around opportunities

During the enforceable period, potential design-around strategies included:

using a non-silicified cellulose excipient;
using a different stabilizing matrix;
incorporating levothyroxine through a different granulation or coating technology;
avoiding separate active and color blends;
changing the manufacturing sequence;
using a non-tablet dosage form;
using alternative excipients, subject to the broader claims.

These routes would need to be assessed claim by claim. Changing only sodium starch glycolate or magnesium stearate would not avoid independent claims 1, 5, 11, or 12.

Legal strength after expiration

The patent has no current exclusionary value. Its remaining value is evidentiary:

it may be prior art against later formulation patents;
it may be relevant to historical FTO opinions;
it may inform invalidity and obviousness analyses;
it may explain past formulation choices;
it may remain relevant to damages periods before expiration.

Does the patent create biosimilar or generic-entry risk today?

No biosimilar issue arises because levothyroxine sodium is a synthetic small-molecule drug. The relevant regulatory pathway is the abbreviated new drug application, or ANDA, not the biosimilar pathway under the Public Health Service Act.

Current generic-entry analysis should focus on:

active ingredient and dosage strength;
therapeutic equivalence;
bioequivalence;
narrow-therapeutic-index considerations;
current Orange Book listings for the relevant reference product;
manufacturing and formulation patents that post-date U.S. Patent 6,399,101;
state substitution and product-switching rules.

FDA has treated levothyroxine as a drug requiring careful control of potency and bioequivalence. The FDA has also taken steps to improve consistency in levothyroxine products and product labeling. [4]

What patent landscape remains relevant after the patent’s expiration?

The relevant landscape is likely to include four categories:

Product-specific formulation patents. These may cover a particular brand’s stability profile, excipient system, dosage form, or manufacturing process.
Method-of-use patents. These may concern treatment of hypothyroidism, thyroid replacement, dosing, or patient populations. Their practical value is limited where the use is conventional or subject to skinny-label strategies.
Manufacturing patents. These may cover blending, granulation, content uniformity, low-dose drug handling, or packaging.
Regulatory exclusivities and product rights. These include NDA exclusivity, approved labeling, trademarks, and commercial contracts rather than patent rights.

For levothyroxine, formulation and manufacturing controls may be more commercially important than broad composition patents because the active ingredient is long-established and generic competition is substantial.

What revenue exposure did the patent create?

The patent could have affected revenue only during its enforceable term and only if:

a marketed product practiced the claims;
the patent was valid and enforceable;
the patent holder had an enforceable ownership position;
a competing product was commercially capable of practicing the claims; and
the patent was asserted or used in settlement negotiations.

The patent did not provide exclusivity over all levothyroxine sodium products. Revenue exposure would therefore have depended on the specific excipient system and manufacturing process used by the branded product.

After October 15, 2019, the patent cannot support a continuing U.S. exclusivity premium. Any current revenue protection must arise from other patents, regulatory exclusivity, trademarks, supply arrangements, clinical differentiation, or manufacturing scale.

Key Takeaways

U.S. Patent 6,399,101 covers stabilized thyroid-hormone preparations using silicified microcrystalline cellulose.
The main commercial target is a levothyroxine sodium tablet containing SMCC.
Claim 5 adds the narrower concept of levothyroxine particles captured and protected within an SMCC matrix.
Claim 12 covers a defined manufacturing sequence involving separate active and color blends.
Sodium starch glycolate and magnesium stearate are covered in narrower dependent claims.
The patent does not claim levothyroxine sodium as a molecule.
The standard patent term ended on October 15, 2019.
The patent is expired and does not present current U.S. generic-entry or biosimilar risk.
Historical Orange Book listing, Paragraph IV challenges, litigation, and settlements cannot be inferred from the claim text alone.
Current levothyroxine FTO analysis should prioritize later product-specific formulation patents, manufacturing patents, Orange Book records, ANDA litigation, and regulatory requirements for therapeutic equivalence.

FAQs About U.S. Patent 6,399,101

Does U.S. Patent 6,399,101 cover all levothyroxine tablets?

No. It requires SMCC, and several claims require additional structural or process limitations. Levothyroxine tablets using other excipient systems are outside the literal scope of the principal claims.

Can a generic manufacturer use silicified microcrystalline cellulose today?

Yes, this patent no longer prevents such use in the United States because its patent term has expired. Other unexpired patents or regulatory requirements must still be evaluated.

Is claim 11 broader than claim 1?

Yes. Claim 11 covers a therapeutically effective amount of a thyroid hormone with SMCC, while claim 1 is limited to levothyroxine sodium.

Does changing magnesium stearate avoid the patent?

Not necessarily. Changing the lubricant may avoid claims specifically requiring magnesium stearate, but it would not by itself avoid independent claims that do not require that lubricant.

Is U.S. Patent 6,399,101 a patent on Synthroid?

No. It is a formulation and manufacturing patent. The patent number alone does not establish ownership by, listing against, or use in Synthroid.

References

United States Patent and Trademark Office. (2002). U.S. Patent No. 6,399,101, Stabilized pharmaceutical preparations containing thyroid hormones.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2013). Guidance for industry: Levothyroxine sodium products, new drug application and abbreviated new drug application sponsors.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2001252953	⤷ Start Trial
Australia	5295301	⤷ Start Trial
Brazil	0109736	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,399,101

Summary for Patent: 6,399,101