US Patent 6,607,748: Scope, Claims, Expiration, and Controlled-Release Starch Patent Landscape

US Patent 6,607,748 covers chemically modified, cross-linked high-amylose starch used as a controlled-release pharmaceutical excipient. Its claims divide into three groups: aqueous manufacturing processes, controlled-release tablets containing the starch, and the starch excipient itself. The patent does not claim a particular active pharmaceutical ingredient or finished drug product.

The patent’s practical significance is now limited by expiration. Based on the patent’s 2000 priority date and 2003 issue date, the ordinary 20-year patent term ended in 2020 or 2021, subject to the patent’s recorded term adjustment and any terminal disclaimer. The claimed technology is therefore generally available for use in the United States, although later patents may protect specific formulations, manufacturing improvements, or commercial products.

What does US Patent 6,607,748 protect?

The patent protects a controlled-release excipient based on high-amylose starch that has undergone:

Cross-linking;
Chemical modification, principally hydroxypropylation;
Gelatinization;
Drying into a powder.

The claims focus on both the manufacturing sequence and the resulting material’s molecular characteristics.

The central claimed concept is a chemically modified, cross-linked high-amylose starch that preserves most of the amylose fraction while limiting cross-linking between amylose and amylopectin. The resulting powder is incorporated into a compressed tablet to control drug release.

The patent claims do not require a specific dissolution profile, release duration, drug loading, tablet hardness, or dosage strength. Instead, they define the excipient through process parameters and analytical characteristics.

What is the patent status and expiration date of US 6,607,748?

Item	Data
U.S. patent	6,607,748
Technology	Chemically modified, cross-linked high-amylose starch excipient
Issue date	August 19, 2003
Priority basis	2000 priority filing, according to the patent record
Patent term	Generally 20 years from the earliest effective nonprovisional filing date
Expected ordinary expiration	Approximately 2020-2021
Current status	Expired by term, subject to confirmation of the official USPTO term record
Orange Book listing	No drug-substance or drug-product listing is expected
Covered products	Excipients, tablets, and manufacturing processes
Regulatory category	Pharmaceutical excipient technology, not an approved active drug

Patent expiration does not eliminate potential exposure under later patents. A manufacturer could practice the expired claims while still infringing a later patent directed to a particular controlled-release formulation, coating, tablet geometry, drug-excipient ratio, or commercial production process.

Under 35 U.S.C. § 154, a U.S. utility patent normally has a term of 20 years from the relevant nonprovisional filing date, with possible adjustment for USPTO delay. The controlling expiration date should be taken from the USPTO patent term data rather than inferred solely from the issue date (U.S. Patent and Trademark Office, n.d.-a).

How many independent claim categories does US 6,607,748 contain?

The patent has three principal independent-claim categories.

Claim category	Claims	Primary subject matter
Manufacturing process, cross-linking before chemical modification	1, 13	Aqueous production of the excipient
Controlled-release tablet	25-39	Compressed blend containing pharmaceutical agent and excipient
Excipient composition	40-43	Chemically modified, cross-linked high-amylose starch defined by analytical properties

Claims 2-12 depend primarily from claim 1 or claim 3. Claims 14-24 depend primarily from claim 13 or claim 15. Claims 29-39 narrow the tablet claims by dosage form, modification, cross-linking agent, excipients, and active ingredient.

The claim set therefore has substantial formal redundancy. Claims 1 and 13 cover opposite process orders:

Claim 1: cross-linking followed by chemical modification.
Claim 13: chemical modification followed by cross-linking.

Claim 2 and claim 14 also preserve simultaneous processing as an alternative. This broadens the process architecture beyond a single reaction sequence.

What manufacturing processes are protected?

Cross-linking followed by chemical modification

Claims 1-12 cover a process in which high-amylose starch is first cross-linked and then chemically modified. The process must occur in an aqueous medium and must include:

Cross-linking of high-amylose starch;
Chemical modification at approximately 10 to 90°C for approximately 1 to 72 hours;
Acid neutralization and washing;
Slurry formation at approximately 2% to 40% w/w;
pH adjustment between approximately 3 and 12;
Gelatinization at approximately 80 to 180°C;
Drying into powder.

Claim 3 narrows the starch to at least 70% amylose and identifies hydroxypropylation with propylene oxide as the chemical modification.

Claim 4 specifies two cross-linking reagents:

Phosphorus oxychloride, at approximately 0.01 to 0.2 g per 100 g starch dry basis;
Sodium trimetaphosphate, at approximately 0.05 to 0.3 g per 100 g starch dry basis.

Claim 6 adds an alkaline cross-linking environment with pH 10 to 14. Claim 7 specifies hydroxypropylation with up to 10% propylene oxide. Claims 9-12 cover direct steam injection and spray-drying conditions.

Chemical modification followed by cross-linking

Claims 13-24 reverse the reaction order. Claim 15 specifically covers:

Hydroxypropylating high-amylose starch with propylene oxide;
Cross-linking the modified starch;
Neutralizing and washing;
Gelatinizing;
Drying.

The reverse-order claims matter because process-order changes can affect substitution level, swelling behavior, tablet compression, and dissolution performance. A manufacturer that avoids the claim 1 sequence could still fall within claim 13 or claim 15.

Simultaneous reaction steps

Claims 2 and 14 cover processes in which cross-linking and chemical modification occur at the same time. These claims reduce the ability to avoid the patent merely by combining reaction steps.

What product characteristics are required by claims 25-43?

Claims 25-28 and 40-43 define the starch through analytical results obtained after solubilization in 90% dimethyl sulfoxide at 80°C for approximately three days, followed by gel permeation chromatography.

The claims require one or more of the following characteristics:

Analytical limitation	Relevant claims
Amylose peak height is at least 90% of the untreated high-amylose starch peak	25, 40
Less than approximately 20% of amylose is cross-linked to amylopectin	26, 41
Less than approximately 20% of amylose is cross-linked to and eluted with amylopectin	27, 42
Amylose peak is higher than the amylopectin-containing peak	28, 43

These limitations distinguish the claimed material from heavily cross-linked starch in which a substantial portion of amylose becomes associated with amylopectin or is no longer separately detected.

For enforcement, the analytical method is important. Infringement testing would likely require:

Sampling the accused excipient or tablet;
Reproducing the stated DMSO dissolution conditions;
Conducting gel permeation chromatography;
Comparing amylose and amylopectin-containing entities;
Establishing that the tested material was made by, or has the characteristics required by, the relevant claim.

The analytical limitations create potential evidentiary disputes involving solvent preparation, temperature control, dissolution time, chromatographic calibration, peak assignment, and batch variability.

What formulation and tablet products are protected?

Claim 25 covers a controlled-release tablet made from a compressed blend containing at least:

A powder of at least one pharmaceutical agent; and
A powder of the controlled-release excipient.

The tablet claims do not require a coating. The release-controlling function is attributed to the starch matrix or excipient.

Claim 29 limits the tablet to oral administration. Claim 30 extends the claim set to an implant, although the use of the term “tablet” may create claim-construction issues depending on the product’s physical form and intended administration.

Claims 31-34 cover specific chemical modifications and cross-linking agents:

Esterification or etherification;
Hydroxypropylation;
Propylene oxide;
Epichlorohydrin;
Adipic acid anhydride;
Sodium trimetaphosphate;
Phosphorus oxychloride.

Claims 35-38 add gelatinization, lubricant, and filler limitations. Magnesium stearate and lactose are expressly identified.

Claim 39 lists a wide range of active ingredients, including pseudoephedrine, acetaminophen, diclofenac, verapamil, glipizide, nifedipine, albuterol, omeprazole, tramadol, ciprofloxacin, oxybutynin, ibuprofen, naproxen, ketorolac, dextromethorphan, and related salts or mixtures.

The active-ingredient list does not create a patent monopoly over those drugs. It narrows the tablet claim to products using the specified drug with the claimed excipient.

How strong are the composition claims?

The composition claims are narrower than the broad process claims because they require both:

A specified preparation sequence; and
A defined analytical property.

Their strength depends on whether the accused product meets the molecular characterization limitations. A product made from a different starch source, using a different modification sequence, could avoid the composition claims if it does not satisfy the amylose or amylopectin relationship.

The analytical limitations also provide a potential design-around route. A competing excipient could use:

Lower or higher amylose content;
Different chemical substituents;
A different cross-linking architecture;
A nonaqueous manufacturing route;
A process that produces a materially different chromatographic profile;
A different release-controlling polymer.

The process claims are broader in operational scope but require more process steps. A manufacturer that uses the claimed reagent ranges, aqueous conditions, gelatinization, and spray-drying may face literal infringement risk if the patent were still enforceable.

What is the Orange Book status of US 6,607,748?

US 6,607,748 is not an Orange Book patent in the conventional sense. The Orange Book lists patents associated with approved drug products, including patents covering drug substances, drug products, and approved methods of use. An excipient patent generally does not qualify for listing unless it is tied to an approved drug product and meets FDA listing requirements.

The patent does not claim:

A new chemical drug substance;
A specific FDA-approved drug product;
A dosage regimen;
A therapeutic indication;
A method of treating a disease.

It is therefore unlikely to have generated Orange Book-based Paragraph IV litigation against a generic drug applicant. Its commercial relevance is primarily in excipient supply, formulation development, manufacturing, and product-level patent analysis rather than Hatch-Waxman exclusivity.

Were Paragraph IV challenges or generic settlements likely?

No Paragraph IV challenge would ordinarily target this patent alone because it is an excipient and manufacturing patent rather than an Orange Book-listed drug patent. A generic applicant could face the patent indirectly if a branded controlled-release product relied on the claimed starch technology and asserted the patent in district court.

The patent’s expiration also removes the principal timing issue. A generic manufacturer does not need a Paragraph IV certification against an expired excipient patent, although it may need to evaluate later patents covering the finished dosage form.

No reliable conclusion about settlement agreements, covenants not to sue, or private licensing arrangements follows from the claim text alone. Such agreements would not necessarily appear in the patent file or Orange Book.

Which companies and technologies are relevant competitors?

The competitive landscape includes suppliers of modified starches, pregelatinized starches, high-amylose starches, cellulose ethers, polyvinyl alcohol, polyethylene oxide, hypromellose, and other hydrophilic matrix polymers.

Technology class	Typical commercial role	Main patent risk
High-amylose starch	Matrix-forming controlled-release excipient	Starch composition and process patents
Pregelatinized starch	Binder, filler, disintegrant	Product-specific excipient patents
Hypromellose	Hydrophilic matrix former	Polymer grade and formulation patents
Polyethylene oxide	High-viscosity release-control polymer	Polymer and dosage-form patents
Ethylcellulose	Water-insoluble matrix or coating	Coating and formulation patents
Polyvinyl alcohol	Matrix and film-forming polymer	Formulation and processing patents
Carbomer and related polymers	Swelling and viscosity control	Polymer grade and combination patents

Relevant commercial suppliers may include starch manufacturers, excipient specialists, and formulation companies. A company’s sale of high-amylose starch does not itself establish infringement. The relevant questions are the starch’s amylose content, chemical modification, cross-link density, analytical profile, and manufacturing sequence.

What manufacturing and intellectual-property barriers remain after expiration?

The expired patent does not remove all barriers to commercial entry. The main remaining barriers are:

Process scale-up for alkaline cross-linking;
Control of substitution and cross-link density;
Removal of residual phosphorus, salts, acids, and propylene oxide-related impurities;
Reproducible gelatinization;
Spray-drying without loss of powder functionality;
Tablet flow, compactability, and storage stability;
Regulatory qualification of the excipient;
Customer-specific performance specifications;
Later patents covering formulations or dosage forms;
Trade secrets covering reaction control and drying conditions.

Propylene oxide handling and residual-control requirements can also increase manufacturing cost. Direct steam injection and spray-drying require equipment capable of controlling temperature, residence time, moisture, and particle morphology.

What generic launch scenarios exist?

Because the patent has expired, a company can generally pursue three entry strategies:

Direct use of the expired technology

The manufacturer can produce a chemically modified, cross-linked high-amylose starch using the disclosed process, subject to later patent review and regulatory controls.

Design-around excipient

The manufacturer can use a different controlled-release polymer or a starch architecture that does not meet the analytical limitations of claims 25-43.

Formulation-specific entry

The manufacturer can use the expired excipient technology but evaluate later patents covering the active ingredient, dosage form, release profile, tablet composition, manufacturing method, or approved method of use.

The highest residual risk typically lies in the finished dosage form rather than the expired excipient process itself.

Key Takeaways

US 6,607,748 covers chemically modified, cross-linked high-amylose starch for controlled-release tablets.
The process claims cover both reaction sequences: cross-linking before modification and modification before cross-linking.
Hydroxypropylation with propylene oxide, phosphorus oxychloride, and sodium trimetaphosphate are central narrowing features.
Product claims depend on gel permeation chromatography and limits on amylose cross-linking to amylopectin.
The patent is not a conventional Orange Book drug patent.
The ordinary patent term appears to have ended around 2020-2021, subject to official USPTO term data.
Paragraph IV litigation would not normally arise against this patent alone.
Later formulation, dosage-form, manufacturing, or active-ingredient patents remain relevant.
The main technical barriers are reaction control, purification, gelatinization, spray-drying, and reproducible tablet performance.

FAQs

Can a company manufacture high-amylose controlled-release starch after US 6,607,748 expires?

Generally yes, provided the company does not infringe later patents covering the same excipient, formulation, manufacturing improvement, or finished dosage form.

Does US 6,607,748 cover all high-amylose starch excipients?

No. Its claims require specified chemical modification, cross-linking, processing, analytical characteristics, or combinations of those limitations.

Does using sodium trimetaphosphate automatically infringe the patent?

No. The reagent is only one claim limitation. Infringement depends on the complete claim, including starch composition, reaction sequence, quantities, processing conditions, gelatinization, drying, and applicable product characteristics.

Can the claimed excipient be used in an implant?

Claim 30 expressly identifies an implant, but the product must still satisfy the limitations of the incorporated tablet and excipient claims.

Is the listed pharmaceutical-agent group an FDA approval list?

No. Claim 39 is a patent claim limitation. Listing an active ingredient in the claim does not establish FDA approval, therapeutic equivalence, or Orange Book eligibility.

References

U.S. Patent No. 6,607,748. (2003). Controlled release excipient. United States Patent and Trademark Office.
U.S. Patent and Trademark Office. (n.d.-a). Patent term adjustment and patent term calculation. https://www.uspto.gov
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
35 U.S.C. § 154. Patent term.
21 C.F.R. § 314.53. Submission of patent information.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	029549	⤷ Start Trial
Austria	328585	⤷ Start Trial
Australia	2001271481	⤷ Start Trial
Australia	7148101	⤷ Start Trial
Brazil	0112140	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,607,748

Summary for Patent: 6,607,748