Details for Patent: 4,264,573

Summary for Patent: 4,264,573

Title:	Pharmaceutical formulation for slow release via controlled surface erosion
Abstract:	A pharmaceutical composition in tablet form for oral administration comprises:(a) 30-90% by weight of an active ingredient having a water solubility (20° C.) of about 1/10-1/500 (w/w);(b) 1-40% by weight of an excipient which is pharmaceutically acceptable in oral tablets and which has a water solubility (20° C.) of about 1/1-1/20 (w/w);(c) 0-20% by weight of a binder which is pharmaceutically acceptable in oral tablets;(d) 0-50% by weight of an excipient which is pharmaceutically acceptable in oral tablets and which has a water solubility (20° C.) of about 1/1-1/5 (w/w);(e) 0.5-5% by weight of a die wall lubricant pharmaceutically acceptable in oral tablets;(f) 0-5% by weight of a surface active agent pharmaceutically acceptable in oral tablets; and(g) 0-1.0% by weight of a disintegration agent pharmaceutically acceptable in oral tablets;whereby the active ingredient has a slow in vivo release rate due to controlled surface erosion of the tablet.
Inventor(s):	David R. Powell, Vithal K. Patel
Assignee:	Rowell Laboratories Inc , Solvay Pharma Properties Inc
Application Number:	US06/040,789
Patent Claim Types: see list of patent claims	Composition; Dosage form;

US Patent 4,264,573: Lithium Carbonate Controlled-Release Tablet Scope, Expiration, and Patent Landscape

US Patent 4,264,573 covers a specific lithium carbonate tablet designed to release lithium through controlled surface erosion. Its core protection is narrow: a high lithium carbonate load combined with defined ranges of sodium chloride or another soluble excipient, polyvinylpyrrolidone or another binder, sorbitol or another more soluble excipient, calcium stearate or another lubricant, sodium lauryl sulfate or another surfactant, and sodium starch glycolate or another disintegrant.

The patent term expired in 1998 under the pre-1995 patent-term regime. It cannot currently block generic manufacture, sale, FDA approval, or use of lithium carbonate extended-release tablets in the United States. Its technical disclosure may still matter for formulation history, freedom-to-operate analysis, and assessment of later patents, but the patent itself has no enforceable US exclusionary term.

What does US Patent 4,264,573 protect?

The patent protects a pharmaceutical tablet containing lithium carbonate in a controlled-release formulation. The claims require both composition and performance characteristics.

Claim	Subject matter	Principal limitations
1	Generic controlled-release lithium carbonate tablet	Defined ranges of seven component categories; slow zero-order in vivo release; plasma profile substantially corresponding to Figure 1; controlled surface erosion
2	Specific composition	Lithium carbonate, sodium chloride, polyvinylpyrrolidone, sorbitol, calcium stearate, sodium lauryl sulfate, and sodium starch glycolate
3	Approximate 300 mg tablet	300 mg lithium carbonate and specified approximate excipient quantities
4	Tablet hardness limitation	Hardness of 5-20 kg; depends on claims 1, 2, or 3

The patent is a formulation patent rather than a patent on lithium carbonate itself. Lithium carbonate is an old active pharmaceutical ingredient, and the patent does not claim its psychiatric use generally, its chemical structure, or lithium therapy as a treatment category.

What are the technical elements of claim 1?

Claim 1 requires a tablet "consisting essentially of" seven formulation components or categories.

Component	Claimed range	Function in the formulation
Lithium carbonate	70-80 wt.%	Active ingredient and principal tablet mass
First soluble excipient	5-15 wt.%	Water-soluble pore-forming or erosion-modifying component
Binder	2-7 wt.%	Granule and tablet cohesion
Second soluble excipient	5-15 wt.%	Controls dissolution, erosion, and tablet structure
Dye wall lubricant	0.9-3.3 wt.%	Lubrication and processing; the claim expressly uses the term "dye wall lubricant"
Surface-active agent	0.1-0.2 wt.%	Wetting and dissolution modulation
Disintegration agent	0.15-0.35 wt.%	Promotes water penetration and controlled breakup or erosion

The listed percentages total approximately 83.05% to 100.5%, depending on the selected values. The claim is therefore written as a formulation range rather than a fixed quantitative recipe.

The claim also requires a functional result: a "slow zero order in vivo release rate" and a plasma concentration/time curve with substantially the same shape as the patent's Figure 1. This performance language narrows the claim, but it can create litigation complexity because the claim does not provide a complete numerical definition of "slow," "zero order," or "substantially the same shape."

How does the "consisting essentially of" language affect infringement?

"Consisting essentially of" is an intermediate transitional phrase. It generally permits unlisted ingredients that do not materially alter the claimed basic and novel characteristics, while excluding additions that materially change those characteristics.

For this patent, the basic and novel characteristics are likely to include:

• high lithium carbonate loading;
• the specified soluble excipient and binder system;
• controlled surface erosion;
• slow, approximately zero-order lithium release; and
• a plasma concentration/time profile corresponding to the disclosed profile.

A formulation containing an additional coating polymer, osmotic agent, release retardant, or substantial alternative matrix former could create an argument that the added material changes the formulation's basic characteristics. A minor processing aid or conventional tablet ingredient would present a different analysis.

The transition does not eliminate the need to satisfy the quantitative ranges. A competing product outside the claimed ranges would not literally meet claim 1 merely because it produces a similar release curve.

What formulation does claim 2 specifically cover?

Claim 2 narrows claim 1 to a named excipient system:

• lithium carbonate;
• sodium chloride;
• polyvinylpyrrolidone, commonly known as PVP or povidone;
• sorbitol;
• calcium stearate;
• sodium lauryl sulfate, commonly known as SLS; and
• sodium starch glycolate.

The claimed ranges remain those in claim 1. A product containing chemically different excipients may avoid literal infringement of claim 2 even if it falls within the broader functional concept of claim 1.

Claim 2 is narrower in ingredient identity but still potentially difficult to analyze because the claim uses functional categories in claim 1 and specific names in claim 2. The relevant questions would include the identity and grade of each excipient, the actual weight percentages, and whether the finished tablet exhibits the required release behavior.

What exact tablet does claim 3 cover?

Claim 3 identifies an approximate 300 mg lithium carbonate tablet:

Ingredient	Approximate amount
Lithium carbonate	300 mg
Sodium chloride	40 mg
Polyvinylpyrrolidone	15 mg
Calcium stearate	9.4 mg
Sodium lauryl sulfate	0.6 mg
Sorbitol	40 mg
Sodium starch glycolate	1 mg

The listed tablet weight is approximately 406 mg. The approximate composition corresponds to the following calculated percentages:

Ingredient	Approximate percentage of 406 mg
Lithium carbonate	73.9%
Sodium chloride	9.9%
Polyvinylpyrrolidone	3.7%
Calcium stearate	2.3%
Sodium lauryl sulfate	0.15%
Sorbitol	9.9%
Sodium starch glycolate	0.25%

Those amounts fall within the ranges recited in claim 2. Claim 3 therefore provides a more commercially recognizable embodiment but remains dependent on the limitations of claims 1 and 2.

"Approximate amounts" creates a tolerance issue. It does not necessarily authorize unlimited variation. In an infringement analysis, the relevant evidence would include the product specification, batch records, manufacturing tolerances, analytical testing, and whether the tablet remains within the claimed functional and compositional boundaries.

What does claim 4 add?

Claim 4 requires a tablet hardness of 5-20 kg and depends on claim 1, 2, or 3.

Hardness is a measurable physical property, but the patent does not identify in the supplied claim text:

• the hardness instrument;
• the test method;
• the number of tablets tested;
• the conditioning or storage conditions; or
• whether the range is an average, a batch range, or an individual-tablet requirement.

That omission could affect enforcement. A product's tablet hardness may vary by manufacturing lot, testing method, compression force, tablet orientation, and environmental conditions.

Claim 4 does not protect every lithium carbonate tablet with hardness within 5-20 kg. The tablet must first satisfy the relevant parent claim.

When did US Patent 4,264,573 expire?

US Patent 4,264,573 expired on April 28, 1998, assuming the ordinary pre-Uruguay Round patent term and no earlier terminal disclaimer or other unusual limitation.

The patent issued on April 28, 1981. For a US patent subject to the former regime, the term was generally 17 years from grant. The current 20-year term measured from the earliest effective nonprovisional filing date applies to later-filed applications, not to an ordinary patent issued in 1981. The governing transition provisions are in 35 U.S.C. § 154.

Event	Date or status
Patent issued	April 28, 1981
Ordinary statutory term	17 years from issue
Projected ordinary expiration	April 28, 1998
Current enforceability	None
Patent-term extension relevance	No practical effect on the expired patent

No current Paragraph IV strategy can be based on this patent because an expired patent cannot support a US infringement action against a later entrant.

What was the FDA and Orange Book significance?

The patent concerns a formulation that could have supported regulatory protection for a branded extended-release lithium carbonate product. Patent listing in the Orange Book, however, is separate from patent validity and enforceability.

The Orange Book framework applies to patents submitted for approved drug products under FDA regulations. A listed patent may cover:

• the active ingredient;
• a drug product or formulation; or
• an approved method of use.

A formulation patent such as US 4,264,573 would most naturally be evaluated as a drug-product patent if it were submitted for an approved lithium carbonate extended-release product. Its listing status would depend on the NDA holder's submission, FDA's listing practices, and the patent's relationship to the approved product.

The patent's expiration means that any historical Orange Book listing would not provide a current barrier to approval or launch. An ANDA applicant would not need to wait for this patent's expiration today, and a Paragraph IV certification directed solely to this patent would have no commercial blocking effect.

FDA approval of a generic lithium carbonate extended-release product still requires product-specific evidence. Bioequivalence is not established solely by matching the ingredient list. The applicant must satisfy the applicable ANDA requirements for the reference product, including release behavior and pharmacokinetic performance where required by FDA.

Does the patent claim a method of using lithium carbonate?

No. The supplied claims do not claim a method of treating bipolar disorder, mania, depression, or another disease. They claim a tablet composition and, in claim 4, a physical tablet-hardness parameter.

The distinction matters:

• The patent does not cover lithium carbonate treatment generally.
• It does not cover a physician's prescription of lithium carbonate.
• It does not cover all extended-release lithium carbonate products.
• It does not cover an alternative composition solely because it has a similar therapeutic indication.
• It may cover a product that meets the exact formulation and release limitations, subject to the patent's expired status.

What release profile does the patent require?

The claims require a slow, zero-order in vivo release rate and a plasma concentration/time curve substantially matching Figure 1.

Zero-order release means that the active ingredient is released at an approximately constant rate over a defined interval. For lithium carbonate, the claimed result is important because lithium has a narrow therapeutic index and clinically relevant toxicity concerns. A controlled profile can reduce peak-to-trough variation compared with immediate-release administration.

The patent appears to rely on controlled surface erosion rather than only on diffusion through an insoluble polymer matrix. The formulation balances:

• soluble excipients that promote erosion and water ingress;
• PVP that improves tablet cohesion;
• calcium stearate that affects lubrication and wetting;
• SLS that improves surface wetting; and
• sodium starch glycolate that promotes controlled disintegration.

The functional limitations could be tested through dissolution studies, in vivo pharmacokinetic studies, and comparison of plasma concentration/time curves. The claim does not appear to define a single dissolution apparatus, medium, agitation speed, sampling schedule, or pharmacokinetic equivalence criterion in the supplied text.

How strong was the patent estate?

The patent estate reflected in the supplied claims is narrow and product-specific.

Strength factor	Assessment
Active ingredient scope	Weak; lithium carbonate itself is not claimed
Therapeutic-use scope	None in the supplied claims
Formulation specificity	High; multiple ingredients and narrow ranges are required
Functional limitation	Significant; requires slow zero-order release and a specified plasma profile
Exact commercial embodiment	Strongest protection appears in claim 3
Physical-property limitation	Claim 4 adds hardness but depends on all parent limitations
Current enforceability	None because the patent expired
Design-around potential	Substantial through excipient substitution, range changes, or different release mechanisms
Current competitive value	Historical and technical, not an enforceable barrier

The most commercially relevant claim is claim 3 because it identifies a recognizable 300 mg tablet. The most legally expansive claim is claim 1, but its breadth is reduced by the required composition ranges and release-profile limitations.

What design-around routes would have existed?

Before expiration, a generic or competing manufacturer could have evaluated several design-around paths:

1. Use a different soluble excipient instead of sodium chloride or sorbitol.
2. Change one or more weight percentages outside the claimed ranges.
3. Replace PVP with another binder.
4. Replace calcium stearate with another lubricant.
5. Replace SLS with another surfactant or omit the surfactant.
6. Use a polymeric matrix, coating, osmotic system, multilayer tablet, or multiparticulate delivery system.
7. Produce a release profile that is not slow zero-order or does not substantially match the disclosed plasma curve.
8. Use a different tablet hardness outside the claim 4 range.

A design-around would need to consider both literal infringement and the doctrine of equivalents. Substituting a chemically different excipient would not automatically avoid all risk if it performs substantially the same function in substantially the same way to produce substantially the same result. The expired status removes that present litigation risk for this patent, but the same formulation changes could matter under later patents.

Which companies are challenging the patent?

There is no current challenge to US Patent 4,264,573 with commercial significance because the patent expired in 1998. Paragraph IV litigation directed to this patent is no longer a meaningful generic-entry issue.

The relevant present-day competitors are manufacturers of lithium carbonate extended-release tablets and products approved through the ANDA pathway. Their risk analysis would focus on:

• patents listed for the current reference product;
• later formulation patents;
• manufacturing patents;
• FDA's product-specific bioequivalence requirements;
• state and federal market-entry obligations; and
• any active patents covering a particular branded extended-release product.

The identity of a current generic manufacturer does not establish infringement or noninfringement of this expired patent.

What litigation and settlement issues affect the patent?

The supplied record does not establish an active US infringement case, settlement, license, or consent judgment involving US Patent 4,264,573. Because the patent expired more than two decades ago, any historical dispute would have no current exclusionary effect.

A historical litigation search would ordinarily examine:

• complaints and answers in the US district courts;
• Federal Circuit opinions;
• Patent Trial and Appeal Board records;
• ANDA Paragraph IV notices;
• FDA Orange Book listing history; and
• SEC filings by branded and generic manufacturers.

No current settlement can extend the life of an expired patent. A private license may allocate historical damages or other contractual rights, but it cannot restore the patent's exclusionary term against the public.

How does this patent compare with later lithium carbonate patent strategies?

US Patent 4,264,573 uses a conventional composition-plus-performance strategy. Later drug patent programs commonly divide protection into several layers:

Patent category	Typical subject matter	Relevance to lithium carbonate products
Composition patent	Specific ingredient combination and ranges	Closest to US 4,264,573
Release-system patent	Matrix, coating, osmotic, multiparticulate, or erosion mechanism	Can cover alternative delivery technology
Manufacturing patent	Granulation, compression, coating, or process parameters	May create manufacturing barriers
Method-of-use patent	Dosing, titration, administration, or disease treatment	Not present in the supplied claims
Device or packaging patent	Delivery device or package configuration	Usually less relevant to conventional tablets
Regulatory exclusivity	FDA statutory exclusivity	Separate from patent rights

The 1981 patent's main weakness is that it concentrates protection in one tablet architecture. A competitor that developed a different release system could potentially avoid the claims, subject to any later patent rights.

What generic launch risks exist today?

This patent creates no current generic launch risk. A company seeking to market lithium carbonate extended-release tablets does not need to wait for US Patent 4,264,573.

The remaining risks are regulatory and commercial:

• demonstrating bioequivalence to the applicable reference product;
• matching the required dosage strength and release characteristics;
• satisfying manufacturing controls for a narrow-therapeutic-index drug;
• avoiding active later patents listed for the relevant reference product;
• obtaining FDA approval through the appropriate pathway; and
• securing adequate commercial scale and supply reliability.

The expired patent may still be useful as prior art. A later patent applicant generally cannot obtain a valid patent merely by repackaging the same disclosed composition without a patentable distinction in formulation, process, performance, or use.

What is the current commercial value of the claimed formulation?

The patent has no current royalty value based solely on enforceable US patent rights. Its remaining value is technical and historical.

Potential business uses of the disclosure include:

• benchmarking a legacy extended-release lithium carbonate formulation;
• identifying prior-art risks for a new formulation;
• comparing excipient systems;
• assessing whether a later patent claims a genuine technical distinction;
• supporting formulation development; and
• evaluating historical branded-product strategies.

Revenue exposure from this patent is zero as a current exclusivity matter. Any commercial value would arise from know-how, manufacturing experience, trademarks, regulatory approvals, or later patents, not from US Patent 4,264,573 itself.

Key Takeaways

• US Patent 4,264,573 claims a controlled-release lithium carbonate tablet, not lithium carbonate or lithium therapy generally.
• Claim 1 requires seven formulation categories, narrow percentage ranges, controlled surface erosion, slow zero-order release, and a defined plasma-profile shape.
• Claim 2 identifies sodium chloride, PVP, sorbitol, calcium stearate, SLS, and sodium starch glycolate.
• Claim 3 covers an approximate 300 mg lithium carbonate tablet with a total weight of about 406 mg.
• Claim 4 requires tablet hardness of 5-20 kg but depends on the other claim limitations.
• The patent issued April 28, 1981, and ordinarily expired April 28, 1998.
• The patent has no current US blocking power and cannot support a current Paragraph IV-based delay.
• No method-of-use claim, biologic claim, biosimilar issue, or active formulation exclusivity remains under this patent.
• Current generic risk depends on FDA bioequivalence requirements and later patents, not this expired patent.
• The patent's principal continuing importance is as prior art and as a technical reference for legacy lithium carbonate controlled-release formulations.

FAQs About US Patent 4,264,573

Does US Patent 4,264,573 still block lithium carbonate extended-release tablets?

No. The patent expired in 1998 and cannot currently block approval, manufacture, or sale of a competing product.

Does the patent cover Lithobid or Eskalith CR?

The claim language may correspond to a historical extended-release lithium carbonate product, but patent coverage must be determined from the product's formulation, approval history, and historical patent submissions. The expired patent cannot currently enforce exclusivity against either product or a generic competitor.

Can a generic use the same excipients after the patent expired?

Yes, from this patent perspective. Other active patents, trade secrets, regulatory obligations, or contractual restrictions could present separate issues.

Is lithium carbonate a narrow-therapeutic-index drug?

Yes. FDA treats lithium carbonate products as requiring careful control of dosage, bioequivalence, manufacturing consistency, and release characteristics. The expired patent does not eliminate those regulatory requirements.

Can a later patent cover the same 300 mg lithium carbonate concept?

A later patent cannot validly reclaim the same disclosed composition without a patentable distinction. It could, however, claim a novel release mechanism, manufacturing process, dosage regimen, particle structure, coating, or demonstrated technical effect.

References

1. United States Patent and Trademark Office. (1981). US Patent No. 4,264,573: Controlled-release pharmaceutical composition. U.S. Department of Commerce.

2. United States Code. (2018). 35 U.S.C. § 154: Contents and term of patent; provisional rights.

3. United States Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.

4. United States Food and Drug Administration. (2021). Product-specific guidances for generic drug development. U.S. Department of Health and Human Services.

5. United States Food and Drug Administration. (2018). Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. U.S. Department of Health and Human Services.

Drugs Protected by US Patent 4,264,573

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate