United States Drug Patent RE44459: Claim Scope, Glipizide Extended-Release Protection, and Patent Landscape

US Patent RE44459 covers controlled-release administration of glipizide for treating hyperglycemia. Its three claims target different aspects of the same product concept: a once-daily or extended-period dosage form that releases glipizide through osmotic, diffusion, or ion-exchange mechanisms.

Claim 1 is broadest in delivery architecture and dosing-rate range. Claim 2 is broad in mechanism but less precise in dosage. Claim 3 is narrower and more product-specific because it requires a once-daily dosage form containing four identified excipients: polyethylene oxide, hydroxypropylmethylcellulose, cellulose acetate, and sodium chloride.

The patent is a formulation and method-of-treatment patent, not a patent on glipizide as a chemical entity. Any enforceability and commercial relevance depend on the patent’s statutory term, reissue history, Orange Book listing history, claim construction, and the relationship between the claimed formulations and the accused product.

What does US Patent RE44459 protect?

RE44459 protects methods of administering glipizide through controlled-release dosage forms. The claims do not cover every glipizide tablet or every treatment of diabetes.

Claim	Core subject matter	Main limitations	Relative breadth
1	Treatment of hyperglycemia	2.0-750 mg glipizide composition; delivery at 10 ng to 25 mg/hour over 24 hours; osmotic or diffusion dosage form	Broad
2	Lowering blood sugar	Oral glipizide composition with pharmaceutically acceptable carrier; release by osmosis, diffusion, or ion exchange	Broad in mechanism, less quantitative
3	Once-daily treatment	2.0-50 mg glipizide; osmotic dosage form; polyethylene oxide, HPMC, cellulose acetate, and sodium chloride	Narrow and formulation-specific

The claims are method claims. A potentially infringing product must be used in a manner that satisfies the relevant treatment and administration limitations. Mere manufacture or sale of glipizide, without the required controlled-release characteristics or intended use, does not automatically satisfy every claim limitation.

How broad is claim 1 of RE44459?

Claim 1 covers a method for treating hyperglycemia using a dosage form that contains 2.0 mg to 750 mg of glipizide and administers the drug at 10 ng to 25 mg per hour over 24 hours.

The claim has five principal elements:

A patient with hyperglycemia.
Administration of a dosage form containing a glipizide composition.
A total composition amount of 2.0-750 mg.
Delivery at 10 ng to 25 mg per hour over an extended 24-hour period.
Delivery through either an osmotic dosage form or a diffusion dosage form.

The rate limitation is unusually broad. At the endpoints, the claimed nominal delivery over 24 hours corresponds to approximately:

Delivery rate	Approximate amount delivered over 24 hours
10 ng/hour	0.00024 mg
1 mg/hour	24 mg
25 mg/hour	600 mg

The claimed composition range and claimed delivery-rate range are separate limitations. A dosage form containing 10 mg of glipizide could fall within the composition range but still avoid the claim if it does not deliver glipizide within the specified rate range or does not use an osmotic or diffusion mechanism.

The claim does not require the full 2.0-750 mg composition amount to be released during the 24-hour period. The language distinguishes the amount present in the dosage form from the rate at which glipizide is administered. That distinction could matter in infringement analysis.

Osmotic dosage forms under claim 1

An osmotic dosage form requires a semipermeable polymer that permits passage of fluid. The claim does not, on its face, restrict the semipermeable polymer to cellulose acetate or require a particular osmotic pump structure.

Potentially relevant design elements include:

A drug-containing compartment;
An osmotic agent or osmogen;
A semipermeable membrane;
A delivery orifice;
A water-permeable but drug-retaining membrane;
A controlled release period approximating 24 hours.

The claim language may capture osmotic systems with different internal configurations if the accused product uses a semipermeable polymer and meets the remaining limitations.

Diffusion dosage forms under claim 1

The diffusion alternative requires a polymer that permits diffusion of glipizide through the polymer. The claim does not specify a particular polymer chemistry, loading level, geometry, or diffusion coefficient.

A matrix tablet, reservoir system, coated multiparticulate, or polymeric membrane system could raise claim 1 issues if glipizide diffuses through the claimed polymer and the product delivers the drug within the stated rate range.

What does claim 2 cover?

Claim 2 covers oral administration of a glipizide composition for lowering blood sugar. The release mechanism must be one of:

Osmosis through a semipermeable membrane;
Diffusion through a polymer permeable to glipizide; or
Ion exchange over time.

Claim 2 does not state the numerical glipizide amount or delivery rate found in claim 1. It also does not require the specific excipient combination in claim 3.

This creates a potentially broad claim scope. The principal vulnerability is that the claim uses functional language rather than detailed structural limitations. A dispute could focus on whether the accused dosage form actually operates by one of the stated mechanisms and whether the administration method produces the claimed blood-sugar-lowering result.

The ion-exchange alternative is materially different from the osmotic and diffusion alternatives. It could cover systems in which glipizide is associated with an ion-exchange material and is released over time through exchange with ions in gastrointestinal fluid. A product that releases glipizide only through dissolution, erosion, or conventional tablet disintegration may not satisfy the ion-exchange limitation.

What formulation does claim 3 protect?

Claim 3 is the most commercially specific claim. It requires:

Treatment of hyperglycemia;
Oral administration;
A once-a-day dosage form;
2.0-50 mg of a glipizide composition;
An osmotic dosage form;
Polyethylene oxide;
Hydroxypropylmethylcellulose;
Cellulose acetate; and
Sodium chloride.

A product that omits any one of the expressly recited excipients would have a strong noninfringement position under the literal wording of claim 3, subject to claim construction and possible doctrine-of-equivalents arguments.

The excipients have different likely technical roles:

Component	Likely formulation role
Polyethylene oxide	Swellable push or drug-layer polymer
Hydroxypropylmethylcellulose	Hydrophilic matrix, binder, viscosity modifier, or release-control polymer
Cellulose acetate	Semipermeable membrane material
Sodium chloride	Osmotic agent or osmogent

The phrase “comprising” generally permits additional ingredients. A competing product could therefore include the four named components plus other excipients and still satisfy the composition limitation if the remaining claim elements are met.

The claim does not expressly recite a delivery orifice, tablet geometry, coating thickness, osmotic pressure, or dissolution profile. Those features may be relevant to infringement only if they are necessary to establish that the dosage form is osmotic or if they appear in the patent specification and affect claim construction.

When does RE44459 lose exclusivity?

A reissue patent generally does not receive a new patent term merely because the Patent Office issued a reissue. Under 35 U.S.C. § 251, the reissue is tied to the term of the original patent, subject to statutory adjustments and any applicable terminal disclaimer. The relevant expiration date must therefore be calculated from the original patent family, filing date, patent term adjustments, and any terminal disclaimer recorded against the patent.

The claims supplied here do not identify:

The original patent number;
The original filing or priority date;
The reissue grant date;
Any patent term adjustment;
Any terminal disclaimer; or
Any later disclaimer or status event.

Those facts control the expiration analysis. The reissue number alone does not establish a later exclusivity date.

For commercial planning, the decisive question is whether RE44459 remains enforceable on the proposed launch date. A reissue claim cannot extend beyond the lawful term of the original patent, and a patent that has expired cannot block a generic launch even if its claims remain technically broad.

What is the Orange Book status of RE44459?

The FDA Orange Book lists patents submitted by an NDA holder for approved drug products. Listing status is product-specific and does not determine validity or infringement. A patent may be technically relevant to a formulation but absent from the Orange Book, or it may be listed against one dosage form but not another. [1]

RE44459 should be evaluated against the Orange Book records for extended-release glipizide products, particularly products corresponding to Glucotrol XL or an equivalent controlled-release glipizide product. The relevant review should distinguish:

Active patent listings;
Delisted patents;
Expired patents;
Method-of-use listings;
Formulation or drug-product listings; and
Patent certifications submitted by ANDA applicants.

The supplied claim text does not establish whether RE44459 is currently listed in the Orange Book. That question requires the FDA’s product-level listing and historical patent-listing records. An Orange Book listing also does not prove that the claims cover a particular generic formulation.

Are Paragraph IV challenges relevant to RE44459?

Yes. If RE44459 was listed for an approved extended-release glipizide product and remained unexpired when an ANDA was filed, a generic applicant could submit a Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed. Under the Hatch-Waxman framework, the NDA holder or patent owner could bring suit within 45 days and obtain a statutory 30-month stay of approval, subject to statutory exceptions and later court orders. [2]

A Paragraph IV analysis would likely focus on:

Obviousness

The challenger could combine prior art involving:

Immediate-release glipizide;
Controlled-release oral antidiabetic products;
Osmotic pump technology;
Diffusion matrices;
Ion-exchange drug delivery; and
The use of polyethylene oxide, cellulose acetate, HPMC, and sodium chloride.

The patent owner would likely rely on the claimed release period, pharmacokinetic control, formulation stability, dose range, and any unexpected clinical or manufacturing result disclosed in the specification.

Written description and enablement

The broad ranges in claim 1 and the mechanism-based language in claim 2 could be tested against the specification. A challenger might argue that the disclosure does not support every combination of:

2.0-750 mg glipizide;
10 ng to 25 mg/hour delivery;
24-hour administration;
Osmotic and diffusion systems; and
Multiple polymer architectures.

The strength of that argument depends on the examples and technical disclosure, not the claim text alone.

Indefiniteness

Potential construction issues include:

“Extended period of 24 hours”;
“Intended lowering of the blood sugar”;
“Polymer permeable to glipizide”;
“Effective blood sugar lowering dose”; and
Whether “administering the glipizide from a dosage form” requires proof of actual release behavior.

Indefiniteness analysis applies the full patent record and the knowledge of a skilled person, not isolated claim phrases. [3]

Reissue-specific issues

Because RE44459 is a reissue patent, an invalidity review should also examine:

Whether the reissue corrected an error within the meaning of 35 U.S.C. § 251;
Whether the reissue broadened claims;
Whether any broadened reissue application was filed within the statutory two-year period;
Whether the reissue violates the recapture rule;
Whether intervening rights apply to activity conducted before the reissue; and
Whether the reissue claims introduced new matter.

The recapture doctrine can invalidate broadened reissue claims that reclaim subject matter surrendered during prosecution of the original patent. [4]

Which companies are challenging RE44459?

The claim text does not identify an ANDA applicant, patent owner, litigation party, settlement counterparty, or court docket. No company-specific Paragraph IV or litigation conclusion can be drawn from the three claims alone.

A complete competitive review would separate four categories:

Category	Relevance
NDA holder	May have listed the patent and initiated Hatch-Waxman litigation
Generic applicant	May have filed Paragraph IV or Section VIII certifications
Formulation developer	May have designed around osmotic, diffusion, or ion-exchange limitations
Licensee or acquirer	May control commercial rights without owning the patent

A patent assignment is not the same as a license, and an Orange Book listing is not evidence of current ownership. USPTO assignment records, FDA listing records, PACER or district-court dockets, and settlement filings must be matched by patent number and product.

How strong is the RE44459 patent estate?

RE44459 has meaningful claim breadth at the level of controlled-release mechanisms, but its practical strength varies by claim.

Strength factor	Assessment
Chemical-entity protection	None apparent
Immediate-release glipizide coverage	None apparent
Controlled-release method coverage	Broad under claims 1 and 2
Specific osmotic formulation coverage	Stronger under claim 3 if all excipients are present
Dose specificity	Claim 1 is broad; claim 3 is narrower
Design-around exposure	Significant, particularly by changing mechanism or excipient system
Biosimilar relevance	None; glipizide is a small molecule
Regulatory leverage	Depends on Orange Book listing and unexpired term
Litigation leverage	Depends on claim construction, validity, and product mapping

The principal commercial weakness is that the claims do not protect glipizide itself. A competitor can potentially avoid the patent by using immediate-release dosing, a different controlled-release mechanism, a non-osmotic formulation, a different polymer system, or a formulation outside the claimed dose and release parameters.

Claim 3 is more difficult to design around if the product uses the listed excipients, but it is also easier to attack through ingredient substitution. A formulation that replaces cellulose acetate, removes polyethylene oxide, or uses a non-osmotic matrix may avoid literal infringement.

How does RE44459 compare with competing glipizide protection?

Protection type	RE44459 position	Competitive implication
Glipizide compound patent	Not covered by the supplied claims	Compound-level exclusivity is separate
Immediate-release tablet	Generally outside the claim focus	Low direct risk
Extended-release formulation	Core subject matter	Highest relevance
Osmotic pump	Expressly covered	Strongest overlap
Diffusion matrix	Expressly covered in claims 1 and 2	Broad design risk
Ion-exchange system	Covered by claim 2	Relevant to alternative controlled-release products
Once-daily 2-50 mg product	Covered by claim 3 if the excipient and osmotic limitations are met	Product-specific risk
Generic manufacturing process	Not expressly claimed	Process risk requires separate patent review
Biosimilar product	Not applicable	Small-molecule ANDA pathway applies

What generic launch scenarios exist for extended-release glipizide?

A generic applicant’s launch scenarios typically depend on the patent status and certification position:

Pre-expiration launch after non-infringement or invalidity success. The applicant prevails in litigation or obtains a judgment removing the patent barrier.
At-risk launch. The applicant launches before final resolution after submitting a Paragraph IV certification. This creates potential damages and injunction exposure.
Post-expiration launch. The applicant waits until the relevant patent term ends.
Design-around launch. The applicant uses a formulation that does not employ the claimed osmotic, diffusion, or ion-exchange mechanism, or avoids the claim 3 excipient combination.
Settlement-based launch. The parties agree to an authorized generic, licensed entry, or negotiated generic launch date. Settlement terms may remain confidential or appear in FTC review materials and court filings.

A generic product can be pharmacologically equivalent to a branded product while using a different release mechanism. Bioequivalence does not establish patent infringement, and patent noninfringement does not establish FDA approval.

Does RE44459 create biosimilar risk?

No. Glipizide is a chemically synthesized small-molecule drug. The principal regulatory pathway for a generic glipizide product is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under section 351(k) of the Public Health Service Act. [1, 5]

The relevant competitive risks are generic substitution, formulation patents, method-of-use claims, manufacturing patents, and regulatory exclusivity. The FDA Purple Book is not the relevant exclusivity database for glipizide. [5]

What manufacturing and geographic barriers does RE44459 create?

The patent is a United States right. It does not, by itself, block manufacture, sale, or use outside the United States. Foreign risk requires a separate family review in each jurisdiction.

Manufacturing activity can create U.S. exposure when it is tied to commercial importation, sale, or use of a product covered by a valid claim. A U.S. ANDA submission can also trigger the statutory safe harbor under 35 U.S.C. § 271(e)(1) for activities reasonably related to FDA approval, although the safe harbor does not authorize commercial launch. [6]

The main technical barriers are likely to involve:

Consistent 24-hour release;
Membrane permeability control;
Osmotic pressure and water influx;
Drug-layer and push-layer manufacture;
Tablet coating and delivery-orifice control;
Polymer substitution;
Scale-up reproducibility; and
Demonstration of bioequivalence for a controlled-release product.

These technical barriers may remain important after patent expiry because controlled-release products can require more complex development and manufacturing than immediate-release tablets.

Key Takeaways

RE44459 is directed to controlled-release glipizide treatment, not the glipizide molecule.
Claim 1 covers osmotic and diffusion dosage forms across broad composition and delivery-rate ranges.
Claim 2 adds ion-exchange delivery and omits the numerical dose limits found in claims 1 and 3.
Claim 3 is narrower but specifically targets a once-daily osmotic dosage form containing polyethylene oxide, HPMC, cellulose acetate, and sodium chloride.
The patent’s commercial effect depends on its original patent term because reissue generally does not create a new term.
Orange Book relevance requires product-specific FDA listing analysis.
Glipizide presents generic, not biosimilar, competition.
The most credible design-around strategies involve changing the release mechanism, polymer system, osmotic architecture, or excipient combination.
A complete litigation and licensing assessment cannot be derived from the claims alone; the controlling evidence is the USPTO family record, FDA listing history, court docket, and assignment record.

FAQs About US Patent RE44459

Is RE44459 a patent on Glucotrol XL?

The claims are consistent with protection for an extended-release glipizide product such as Glucotrol XL, but the claims alone do not establish the product listing, ownership chain, or current Orange Book status.

Can an immediate-release glipizide generic infringe RE44459?

An immediate-release product would generally lack the claimed osmotic, diffusion, or ion-exchange controlled-release limitations. Infringement would require analysis of the actual product and the asserted claim.

Can a generic use the same four excipients and avoid claim 3?

Not necessarily. Claim 3 uses “comprising” language and may permit additional ingredients. Avoiding infringement would require assessing all limitations, including the once-daily dosage form, osmotic mechanism, dose range, and four named components.

Does a Paragraph IV certification invalidate RE44459?

No. A Paragraph IV certification is an applicant’s legal position that a listed patent is invalid, unenforceable, or not infringed. The certification can trigger litigation but does not itself cancel the patent.

Can RE44459 block a glipizide product outside the United States?

No. A U.S. patent has no direct legal effect in foreign countries. Foreign blocking rights require corresponding patents in the relevant jurisdictions.

References

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
Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).
35 U.S.C. § 112.
U.S. Patent and Trademark Office. (2023). Manual of Patent Examining Procedure § 1412: Reissue patent. https://www.uspto.gov/web/offices/pac/mpep/
U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov/
35 U.S.C. § 271(e)(1).
United States Patent and Trademark Office. (n.d.). Patent Center: U.S. Patent RE44459. https://patentcenter.uspto.gov/

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
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Details for Patent: RE44459

Summary for Patent: RE44459