Details for Patent: 5,266,325

Summary for Patent: 5,266,325

Title:	Preparation of homogeneous hydrogel copolymers
Abstract:	A method is provided for the preparation of homogeneous copolymers having a predetermined equilibrium water content (EWC) value formed by the addition polymerization of a mixture of ethylenically unsaturated monomer A and ethylenically unsaturated monomer B, for example, 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate. The method requires determining the EWC values of the hydrogel homopolymer of hydrophilic monomer A (homopolymer A) and the hydrogel homopolymer of hydrophilic monomer B (homopolymer B); determining the relationship of the EWC values of the homogeneous copolymers AB versus the chemical composition of said copolymers AB; selecting the targeted EWC value and determining the chemical composition of copolymer AB having the targeted EWC value; forming a polymerizable mixture of monomer A and monomer B in amounts sufficient to yield copolymer AB having the targeted EWC value; and effect the polymerization reaction to yield copolymer AB characterized by the targeted EWC value. A method is also provided for the preparation of a delivery device including a drug contained in the reservoir of the hydrogel of copolymer AB, said device being characterized by its capability of eluting or releasing the drug through the hydrogel membrane to a delivery environment at a predetermined rate. There is also disclosed a sterilized kit containing a trocar or hypodermic needle/syringe and the aforesaid drug delivery device having a cylindrical shape with a rounded or bullet-like extremity.
Inventor(s):	Petr Kuzma, Daniel G. Moro, Harry Quandt
Assignee:	Sanyo Electric Co Ltd , Endo Pharmaceuticals Solutions Inc
Application Number:	US07/621,346
Patent Claim Types: see list of patent claims	Use; Composition; Delivery; Device;

United States Patent 5,266,325: Claim Scope, Expiration, and Drug-Delivery Patent Landscape

U.S. Patent No. 5,266,325 protects a hydrogel or xerogel implant platform for sustained drug delivery. Its central technology combines a 2-hydroxyethyl methacrylate, or HEMA, copolymer cartridge with a higher-equilibrium-water-content polymer plug. The patent also covers centrifugal casting, implantable cartridges, protein and peptide payloads, implantation by hollow needle, and sterilized implantation kits.

The patent is a device and manufacturing patent, not a patent claiming a particular pharmaceutical molecule. Its practical exclusionary value depended on use of the claimed cartridge, plug, loading, and implantation architecture. The patent’s original term has expired, eliminating current U.S. blocking rights based solely on this patent.[1]

What does U.S. Patent 5,266,325 protect?

The patent has four principal claim groups:

Claim group	Claims	Protected subject matter
Copolymer manufacturing	1-7, 18	Selecting monomer composition by equilibrium water content and centrifugally casting a uniform cylindrical cartridge
Cartridge article	19-24	HEMA-based hydrophilic cartridge with a reservoir, smooth surfaces, uniform wall thickness, and specified geometry
Drug-delivery device	8-17, 25-33	Cartridge, drug reservoir, higher-EWC polymer plug, and sustained-release configuration
Implantation and kit	34-40	Subcutaneous delivery through a hollow needle and a sterilized aqueous implantation kit

The independent claims are claims 1, 8, 19, 25, 34, and 39. The broadest commercial protection resides in claims 19 and 25 because they are directed to the cartridge and finished delivery device rather than only to a manufacturing process.

What is the core inventive concept?

The core concept is a cylindrical, non-biodegradable, water-swellable polymer cartridge that controls drug diffusion through its walls. The cartridge is loaded through an opening and sealed with a polymer plug having a higher EWC than the cartridge. The difference in water uptake is used to create a plug that permits hydration while closing the reservoir.

Claim 1 adds a process for predicting and selecting the copolymer composition:

1. Measure the EWC of the homopolymers.
2. Establish the relationship between copolymer composition and EWC.
3. Select a target EWC.
4. Prepare the corresponding monomer mixture.
5. Fill a cylindrical tube.
6. Rotate the tube horizontally to distribute the liquid radially.
7. Polymerize the liquid into a hollow cartridge.
8. Recover a uniform cylindrical copolymer.

This process limitation is narrower than the product claims. A competing manufacturer could avoid claim 1 by using a different molding, machining, extrusion, or casting process, although the resulting device could still implicate claims 19 or 25.

What chemical compositions are covered?

Claims 2-5 and 19-24 focus on HEMA-based copolymers.

Limitation	Claimed range
HEMA in claim 2	About 25-75 wt%
Monomer B in claim 2	About 75-30 wt%
Target EWC in claims 2 and 4	About 25-75 wt%
HEMA in claim 4 and claim 19	About 25-70 wt%
Monomer B in claim 4 and claim 19	About 75-30 wt%
EWC in claims 3, 5, and 20	About 26-33 wt%
Expressly identified monomer B	Hydroxypropyl methacrylate, or HPMA

The language "consisting essentially of" narrows the permissible composition compared with "comprising." It generally permits components that do not materially alter the claimed characteristics, but it creates a meaningful litigation issue for crosslinkers, initiators, pore-forming agents, plasticizers, dyes, stabilizers, and other additives.

Claim 18 expressly permits a water-soluble pore-forming agent in the polymerizable mixture. The patent therefore contemplates porosity as a method of modifying permeability and release rate.

Does the patent require both HEMA and HPMA?

Not in every claim. Claims 2-5 and 20 expressly identify HEMA and, in narrower claims, HPMA. Claim 19 requires HEMA units and "monomer B units," but claim 20 narrows monomer B to HPMA. Claims 1 and 8 refer more generally to monomers A and B, subject to the other limitations of the claims.

A product using HEMA with a different hydrophilic comonomer could fall outside the HPMA-specific claims while potentially remaining within a broader claim, depending on claim construction and the full composition.

What product features are required by the cartridge claims?

Claim 19 requires a cartridge with the following characteristics:

• Biocompatible;
• Non-biodegradable;
• Water-swellable;
• Water-insoluble;
• Hydrophilic;
• A reservoir or core;
• An oval cylindrical shape at the closed end;
• An open end;
• Smooth internal and external cylindrical surfaces;
• Uniform wall thickness;
• HEMA and monomer B units;
• EWC of approximately 25-75 wt%.

The geometry is material. A flat membrane, irregular reservoir, porous pellet, conventional capsule, or multilayer laminate would not necessarily satisfy the cartridge claim.

Claim 24 adds a specialized surface treatment. The internal surface near the open end is scored and treated with a mono- or polyhydric alcohol to promote graft polymerization of an additional ethylenically unsaturated monomer. This limitation appears directed to improving attachment of the sealant plug to the cartridge.

How important is the smooth oval cylindrical shape?

It is important to the literal scope of the narrower article and device claims. The patent does not merely claim any hydrogel implant. It claims a particular reservoir geometry suitable for insertion through a hollow needle and subcutaneous placement.

Claims 9 and 10 separately address oval shaping of the device. Claim 10 permits shaping the portion distal to the plug after loading and sealing. This supports a manufacturing sequence in which the cartridge is first formed, filled and sealed, then finished into an implantable oval profile.

What does the polymer plug claim cover?

Claims 8 and 25 require a plug or sealant with an EWC greater than that of the cartridge.

The plug must be:

• Biocompatible;
• Non-biodegradable;
• Water-swellable;
• Water-insoluble;
• Hydrophilic;
• Polymerized in the cartridge opening or used as the sealant means.

This limitation distinguishes the claimed device from a metal crimp, elastomeric stopper, adhesive cap, impermeable polymer end wall, or mechanically fitted plug.

The plug is not merely packaging. It is part of the release system. The claims require that the active agent be contained in the cartridge reservoir and that the plug close the opening while participating in the hydrated polymer structure.

What drugs and biological agents are covered?

Claims 11-15, 26, and 29-32 identify broad classes of payloads:

• Drugs generally;
• Native bioactive proteins;
• Recombinant bioactive proteins;
• Hormonally active polypeptides;
• Luteinizing hormone-releasing hormone, or LHRH;
• Mammalian growth hormone;
• Mammalian growth-releasing hormone.

These claims do not create composition-of-matter rights in the listed molecules. They limit the claimed device or method when used with those payloads.

A generic drug manufacturer that sells an injectable LHRH product without the patented implant architecture would not practice these device claims merely because the active ingredient is the same. Conversely, an implant manufacturer could face infringement issues if it uses the claimed HEMA/HPMA cartridge and higher-EWC polymer plug with an LHRH or protein payload.

What are the principal infringement risks?

Literal infringement

The strongest literal-risk scenarios involve a product that has all or most of the following characteristics:

1. A HEMA/HPMA hydrophilic cartridge.
2. EWC within the claimed range.
3. A hollow cylindrical reservoir.
4. Uniform wall thickness and smooth surfaces.
5. A polymer plug with higher EWC.
6. Sustained release of a drug or protein.
7. Subcutaneous insertion through a hollow needle.

A product lacking the HEMA/HPMA composition may avoid the narrow claims but still require analysis of broader process claims and any related patent family members.

Doctrine of equivalents

A materially different hydrophilic comonomer, equivalent polymer plug, or alternative production process could raise doctrine-of-equivalents issues. The risk would depend on prosecution-history estoppel, claim amendments, prior-art positions, and whether the substituted feature performs substantially the same function in substantially the same way.

Because the claims include detailed composition, EWC, geometry, and manufacturing limitations, prosecution-history estoppel could be significant. Narrow numerical ranges and expressly recited monomers generally create stronger arguments against expanding the claims to substantially different compositions.

Product-by-process exposure

Claim 1 is a process claim. It requires the EWC-selection workflow and centrifugal casting steps. A finished product cannot be assessed solely from its physical appearance for process-claim infringement unless the accused product is made by the claimed process. Claims 19 and 25 provide more direct product-based exposure.

When did U.S. Patent 5,266,325 lose exclusivity?

U.S. Patent No. 5,266,325 issued on November 30, 1993.[1] Because it issued before the Uruguay Round Agreements Act changed the standard U.S. patent term, its ordinary term was generally 17 years from grant, subject to any applicable adjustment, disclaimer, or extension. On that basis, the ordinary expiration date was November 30, 2010.

The patent is therefore expired. No current Paragraph IV challenge is required to practice the expired claims. A party launching a product today would instead assess:

• Related continuation or divisional patents;
• Terminal disclaimers;
• Foreign counterparts;
• Later patents on specific drugs or formulations;
• Manufacturing patents;
• Regulatory exclusivity;
• Trade-secret restrictions;
• Any separate patent family covering an improved implant system.

The expired status also means that the patent should not create current U.S. royalty leverage by itself.

What is the Orange Book status of U.S. Patent 5,266,325?

The patent is not a conventional Orange Book drug patent. The claims are directed to a polymer cartridge, delivery device, manufacturing method, implantation procedure, and kit. They do not claim an approved active ingredient, drug formulation, or method of use in the standard Orange Book sense.

FDA Orange Book patent listing is tied to approved drug products and patents that claim the drug, formulation or composition, or an approved method of use.[2] A historical device patent of this type would not ordinarily create an Orange Book-listed barrier for an abbreviated new drug application directed to the same active ingredient in a conventional dosage form.

The patent also does not establish FDA approval. FDA approval would depend on the specific drug-device combination, route of administration, clinical data, manufacturing controls, biocompatibility, sterility, and applicable combination-product requirements.[3]

Are Paragraph IV challenges relevant?

Paragraph IV is generally relevant only when an ANDA applicant certifies against patents listed for an approved reference drug under the Hatch-Waxman framework.[4] Patent 5,266,325 is not, based on its claim subject matter, a conventional active-ingredient or formulation patent.

Its relevance would be stronger in a drug-device product approved with an implant delivery system if the patent had been listed against that reference product while unexpired. Since the patent expired in 2010, a current Paragraph IV dispute based solely on this patent would not be commercially meaningful.

A drug sponsor could still face separate patent litigation involving:

• A specific peptide or hormone;
• Long-acting formulations;
• Implant geometry;
• Release-rate control;
• Manufacturing of the drug-device combination;
• Use of a particular implant for an approved indication.

Those rights would arise from other patents, not automatically from Patent 5,266,325.

How does this patent compare with competing implant technologies?

Technology	Typical reservoir or matrix	Release mechanism	Relationship to Patent 5,266,325
HEMA/HPMA hydrogel cartridge	Hydrophilic polymer reservoir	Diffusion through hydrated polymer	Directly aligned with the patent
Silicone matrix implant	Silicone elastomer matrix or rod	Diffusion through silicone	Generally outside the HEMA-specific claims
Osmotic implant	Drug reservoir with semipermeable membrane	Osmotic pressure and controlled pumping	Technically distinct
Biodegradable microspheres	Polymer matrix or microspheres	Polymer erosion and diffusion	Generally outside the non-biodegradable cartridge claims
Metal or glass reservoir	Rigid container with membrane or port	Membrane-controlled diffusion	May avoid hydrogel limitations
Coated implant rod	Core plus polymer coating	Diffusion through coating	Depends on composition and geometry

The closest technical competitors are other non-biodegradable implant systems that use a polymer barrier to regulate diffusion. The patent is less relevant to biodegradable depots, microspheres, transdermal systems, oral sustained-release products, and conventional injectables.

What biosimilar and generic-entry risks exist?

The patent creates no current biosimilar barrier by itself. Biosimilar applicants are generally concerned with patents covering the biologic molecule, formulation, manufacturing process, delivery device, and approved method of use. Patent 5,266,325 does not claim a protein sequence or biologic composition.

For generic drugs, the patent presents the same distinction. A conventional tablet, injection, or vial containing the same active agent would not practice the claimed implant device. A generic or follow-on applicant pursuing an implantable sustained-release product would need to conduct a freedom-to-operate review of later device, formulation, and manufacturing patents.

What licensing or litigation issues remain?

The claims do not identify any licensee, settlement, or commercial partner. The patent number alone does not establish a continuing royalty obligation after expiration.

Historical litigation or licensing could still matter for:

• Contractual royalty audits;
• Patent-family ownership;
• Assignments;
• Confidential know-how;
• Improvements developed under a license;
• Foreign counterpart patents that had different expiration dates.

Those issues are separate from the expired U.S. claims. An expired patent cannot support a new U.S. patent-infringement claim for post-expiration conduct, although pre-expiration conduct may remain subject to applicable limitation periods and litigation rules.[5]

How strong is the patent estate?

The patent was technically specific but commercially concentrated.

Strength factor	Assessment
Core device concept	Moderate to strong during the original term
Chemical scope	Narrow because of HEMA, HPMA, and EWC limitations
Process scope	Narrower than product claims because of centrifugal casting requirements
Payload scope	Broad in category but dependent on the device architecture
Orange Book leverage	Low
Current U.S. blocking power	None after expiration
Biosimilar relevance	Low unless the product uses the claimed implant design
Design-around potential	Meaningful through different polymers, plugs, geometries, or manufacturing methods
Commercial value today	Historical and defensive rather than exclusionary

Key Takeaways

• U.S. Patent 5,266,325 covers a HEMA-based hydrophilic implant cartridge, particularly HEMA/HPMA copolymers with specified EWC ranges.
• Its main commercial claims cover the cartridge, higher-EWC polymer plug, drug reservoir, subcutaneous implantation method, and sterilized kit.
• The patent does not claim LHRH, growth hormone, recombinant proteins, or other drugs as compositions of matter.
• It is not a conventional Orange Book drug patent.
• The patent issued November 30, 1993 and reached its ordinary 17-year expiration on November 30, 2010.
• No current U.S. exclusivity or Paragraph IV barrier remains from this patent alone.
• The strongest historical infringement risk involved implantable devices using the claimed HEMA/HPMA cartridge and polymer-plug architecture.
• Current freedom-to-operate analysis must focus on later continuation patents, improvement patents, formulation patents, device patents, and foreign rights.

FAQs

Does Patent 5,266,325 cover all hydrogel drug implants?

No. Its claims are limited by specific structural, chemical, EWC, geometry, plug, and manufacturing requirements. Many hydrogel implants using different polymers or device architectures would fall outside its literal scope.

Can a company sell an HEMA hydrogel implant after the patent expired?

Yes, this patent no longer provides an enforceable U.S. exclusionary right. The product may still implicate later patents covering the specific drug, formulation, implant design, manufacturing process, or release profile.

Does the patent cover a standard LHRH injection?

No. The LHRH claims are dependent on the claimed delivery-device architecture. A conventional injectable LHRH product does not practice the cartridge, plug, and implantation limitations.

Is centrifugal casting required for every claim?

No. Centrifugal casting is central to claim 1 and related process claims. The article and delivery-device claims contain separate structural limitations and do not automatically require the accused product to have been made by the claim 1 process.

Does the patent provide patent protection for recombinant growth hormone?

Only as an active agent used in the claimed delivery device or implantation method. It does not provide composition-of-matter protection for recombinant growth hormone itself.

References

1. United States Patent and Trademark Office. (1993). U.S. Patent No. 5,266,325.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2024). Combination products.
4. U.S. Code, 21 U.S.C. § 355(j).
5. U.S. Code, 35 U.S.C. §§ 154, 271, 286.

Drugs Protected by US Patent 5,266,325

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

International Family Members for US Patent 5,266,325

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	149345
Australia	1018392
Australia	651654