US Patent 4,767,628: Claim Scope, Expiration, and Polylactide-Polypeptide Patent Landscape

US Patent 4,767,628 covers biodegradable polylactide and polylactide-glycolide compositions containing pharmacologically active polypeptides. Its central limitation is a controlled-release mechanism in which initial diffusion through water-filled peptide domains overlaps with later release caused by polymer degradation. The patent was granted on August 30, 1988, and its ordinary 17-year patent term expired on August 30, 2005. The patent therefore presents no current blocking right in the United States, although its claims remain relevant as prior art and as a technical reference for biodegradable peptide delivery systems. [1, 2]

What does US Patent 4,767,628 protect?

The patent protects a pharmaceutical composition containing two principal components:

A polylactide-based biodegradable polymer.
A pharmacologically active polypeptide uniformly dispersed in that polymer.

The polymer may be:

Polylactic acid alone;
A copolymer of lactic acid and glycolic acid;
A mixture of polylactide polymers;
A mixture of polylactide-glycolide copolymers; or
A mixture of polymers and copolymers.

The claims permit racemic or optically active lactic acid. They also define the polymer by solvent solubility and inherent viscosity, rather than solely by molecular weight or monomer composition.

The protected delivery system has a required two-stage release profile:

An initial diffusion phase through aqueous peptide domains and channels that communicate with the composition's exterior surface.
A later degradation-induced phase caused by hydrolysis and erosion of the polylactide matrix.

The phases must overlap in time. This functional requirement is central to claim 1 and narrows the claim compared with a generic claim to a peptide embedded in PLGA.

How broad is independent claim 1?

Claim 1 is the principal composition claim and has five major limitations.

Claim element	Scope
Polymer identity	Polylactide, lactide-glycolide copolymer, or specified mixtures
Polymer composition	Glycolide-to-lactide ratio from 0 to 3:1
Polymer viscosity	Ranges vary by benzene solubility and solvent
Active agent	Pharmacologically active polypeptide with at least about four amino acid residues
Release mechanism	Diffusion through aqueous peptide domains followed by polymer degradation, with temporal overlap

The claim is broad with respect to the active peptide. It is not limited to one therapeutic indication, route of administration, particle geometry, or manufacturing process. It can cover compositions containing many peptide hormones, growth factors, gastrointestinal peptides, neuropeptides, antibiotics of peptide character, and synthetic analogues.

The claim is narrower with respect to polymer behavior. A formulation must satisfy the specified polymer identity, composition, inherent-viscosity parameters, and release behavior. A product that contains PLGA and a peptide but releases the peptide through a materially different mechanism may fall outside the literal scope of claim 1.

The phrase "uniformly dispersed" supports a matrix formulation rather than a simple surface coating, reservoir system, or physically separate drug layer. The claim also requires water partitioning between the polymer and polypeptide to create aqueous peptide domains that eventually form communicating channels.

What formulations are protected by claims 2 through 17?

The dependent claims create narrower composition groups based on peptide identity, molecular weight, polymer viscosity, glycolide content, and peptide loading.

Claims	Covered formulation category
2	Listed peptides and analogues, including oxytocin, vasopressin, ACTH, EGF, insulin, somatostatin, glucagon, interferon, gastrin, calcitonin, enkephalins, and others
3-5	Polypeptides below 2,000 molecular weight, with different polymer-viscosity bands
6-8	Polypeptides with molecular weight from 1,500 to 10,000
9-11	Polypeptides with molecular weight from 8,000 to 30,000
12-14	A specified synthetic luliberin or LHRH analogue with molecular weight 1,269
15-16	Epidermal growth factor or urogastrone
17	Injectable suspension containing fine particles of the claim 1 solid formulation in a liquid carrier

Claims 3 through 11 use composition ranges to correlate peptide molecular weight and polymer viscosity with release behavior. Higher-molecular-weight peptides are generally paired with narrower loading and viscosity ranges in some claims, although the claims are not consistently organized as a single formulation-design rule.

Claim 17 is commercially important because it reaches an injectable suspension rather than only the underlying solid matrix. It requires:

1% to 50% by weight of the solid biodegradable formulation;
50% to 99% by weight of an injectable liquid carrier;
Fine particle size; and
A polylactide composition with the specified glycolide-to-lactide ratio and viscosity characteristics.

Which claim limitations are most important in an infringement analysis?

The highest-value limitations are the release mechanism, polymer viscosity, polymer composition, and uniform dispersion requirement.

Polymer composition

The claims cover lactic acid polymers and copolymers with glycolide-to-lactide ratios up to 3:1. Claims 3, 4, 6, 7, and 10 impose narrower lower bounds on glycolide content. A product using a polymer outside the relevant ratio may avoid a claim, subject to the doctrine of equivalents.

The claim language appears to use "ratio of glycolide to lactide units." A technical comparison would require polymer composition data based on actual repeat-unit content, not only a supplier's commercial grade designation.

Inherent viscosity

Inherent viscosity is a direct claim variable. The relevant ranges include:

Less than 0.1;
Less than 0.15;
Less than 0.2;
0.15 to 0.4;
0.2 to 0.5;
0.4 to 0.8; and
Greater than 0.5.

Because viscosity depends on solvent, concentration, temperature, polymer molecular-weight distribution, and test method, the claim specifies solvents and concentrations. An accused product would require testing under the stated conditions. A viscosity value from a different analytical method may not be directly comparable.

Polypeptide identity and stability

Claim 1 requires a polypeptide with at least approximately four amino acid residues and sufficient stability during the intended use period. Claim 2 lists specific peptide classes and analogues, but the list does not appear to limit claim 1 to those compounds.

The term "not significantly hydrolyzed" is functional and potentially contestable. The analysis would focus on the intended use period, hydrolysis conditions inside the matrix, assay method, and the degree of degradation considered significant.

Overlapping release phases

The product must exhibit both diffusion-controlled and degradation-induced release, with temporal overlap. A formulation that has only burst release followed by polymer erosion may not meet the claim if the required aqueous-channel diffusion mechanism is absent. Conversely, a formulation with peptide diffusion that continues while polymer molecular weight declines and mass loss begins may present a stronger literal-infringement case.

How strong is the patent estate for US 4,767,628?

The patent's original claim set was technically broad but legally vulnerable in several areas.

Strength factor	Assessment
Therapeutic breadth	Broad, because claim 1 is not limited to one peptide or indication
Polymer coverage	Broad within specified polylactide and glycolide ranges
Product-formulation coverage	Stronger for matrix formulations and injectable suspensions
Functional release limitation	Narrows claim scope and creates proof burdens
Manufacturing coverage	Limited; the supplied claims are composition claims, not process claims
Device coverage	No clear claim to a particular implant, syringe, injector, or microsphere apparatus
Current enforceability	None after expiration
Prior-art value	High for biodegradable peptide-delivery formulations

The principal validity pressure points would have included written description, enablement, indefiniteness, anticipation, and obviousness. Claim 1 reaches a large universe of polypeptides and polymer combinations while requiring a complex functional release profile. A challenger could have argued that the specification did not enable the full breadth without undue experimentation. Terms such as "about," "not significantly hydrolyzed," "sufficient level," and "substantially all" could also have generated claim-construction disputes.

The patent's technical disclosure would have been important in defending against those arguments. Experimental examples showing overlapping diffusion and degradation release across multiple polymers and peptides would strengthen the claims. Results limited to a narrow set of formulations would weaken the broader genus claims.

When did US 4,767,628 lose exclusivity?

US 4,767,628 was granted August 30, 1988. For a pre-June 8, 1995 application, the ordinary United States term was 17 years from grant under the then-applicable patent-term rule. On that basis, the patent expired August 30, 2005. [1, 3]

Event	Date
Patent grant	August 30, 1988
Ordinary patent term	17 years from grant
Expiration	August 30, 2005
Current enforceability	Expired

Patent-term restoration could extend certain pharmaceutical patents under 35 U.S.C. § 156, but restoration is product-specific and would require an identified qualifying regulatory approval. Nothing in the supplied claims establishes such an extension. The patent should therefore be treated as expired unless an official patent-term record shows otherwise. [3]

What is the Orange Book status of US 4,767,628?

US 4,767,628 is not a current Orange Book barrier. The Orange Book lists patents submitted for approved drug products and identifies patent and exclusivity information relevant to abbreviated new drug applications. A broad platform patent covering polylactide-polypeptide matrices is not, by itself, an Orange Book-listed drug patent. [4]

The patent also does not create a current Paragraph IV risk. Paragraph IV certifications address patents listed for a reference drug in the Orange Book. Because this patent expired in 2005 and is not a current product-specific exclusivity right, a generic applicant would not need to challenge it as an active Orange Book patent.

Which companies or products are most relevant to the patent landscape?

The commercial landscape includes long-acting peptide and protein products using PLGA or related biodegradable delivery systems. Relevant products and developers include:

Product or platform	Active agent	Delivery relevance
Lupron Depot	Leuprolide acetate	Long-acting biodegradable microsphere technology
Sandostatin LAR	Octreotide acetate	Depot microsphere delivery
Vivitrol	Naltrexone	PLGA injectable microsphere delivery, non-peptide active
Bydureon	Exenatide	Extended-release PLGA microsphere formulation
Decapeptyl	Triptorelin	Long-acting GnRH analogue depot
Eligard	Leuprolide acetate	Atrigel in situ depot system, distinct from classic microspheres
Somatuline Depot	Lanreotide	Long-acting peptide depot, different formulation architecture

These products may involve later patents directed to:

Particle size and morphology;
Encapsulation efficiency;
Residual solvent control;
Peptide stabilization;
Surfactants and excipients;
Reconstitution systems;
Injection force;
Release-rate control;
Manufacturing scale-up;
Sterility and aseptic processing; and
Specific indications or dosing schedules.

A product can therefore be outside the expired patent's literal scope yet remain protected by later formulation, process, method-of-use, or device patents.

How does this patent compare with later PLGA formulation patents?

US 4,767,628 is principally a composition-and-release-mechanism patent. Later patent estates commonly narrow the focus to commercially reproducible attributes.

Issue	US 4,767,628	Later PLGA estates
Active agent	Broad polypeptide genus and listed species	Often one peptide or analogue
Polymer	Broad polylactide/PLGA classes	Defined lactide:glycolide ratio, end groups, molecular weight
Release profile	Functional overlap of diffusion and degradation	Quantified release windows and in vitro specifications
Particle characteristics	Fine particles in claim 17	Specific D50, morphology, porosity, and distribution
Manufacturing	Minimal claim coverage in supplied claims	Emulsion, spray drying, solvent extraction, and scale-up processes
Commercial product	Broad platform	Product-specific formulation and dosage claims
Current term	Expired	May remain active depending on filing date and patent family

The principal freedom-to-operate issue has shifted from the expired platform claim to later patents covering the exact commercial formulation and manufacturing process.

What generic launch risks exist?

The direct risk from US 4,767,628 is zero as an enforceable patent risk because the patent expired. The remaining risks are commercial and technical:

Later patents may cover the approved product's formulation or manufacturing process.
FDA approval may require demonstrating comparable drug release, particle characteristics, sterility, and clinical performance.
Peptide stability during encapsulation and storage can create development barriers.
Injectable PLGA products require specialized manufacturing and analytical controls.
A generic or follow-on applicant may face limited competition from complex-product requirements even without an active platform patent.

For peptide depots, the regulatory pathway may involve an abbreviated new drug application, a 505(b)(2) application, or a biologics pathway depending on the active ingredient and reference product. The patent analysis must be product-specific. A formulation patent not listed in the Orange Book can still create litigation exposure through ordinary patent infringement litigation, although it cannot support a Paragraph IV certification unless listed for the relevant drug. [4, 5]

What biosimilar risk is relevant?

Traditional biosimilar risk is limited because the patent claims concern delivery compositions rather than an innovator biologic molecule. The relevant competitive category may instead include:

Generic complex injectables;
505(b)(2) depot products;
Follow-on peptide formulations; and
Biosimilar or interchangeable biologics using separate delivery systems.

A biosimilar applicant would analyze patents covering the biologic, formulation, administration method, device, and manufacturing process. US 4,767,628 would generally be treated as expired prior art, not as a live biosimilar barrier. The FDA Purple Book identifies biologic exclusivity and biosimilar-related information, but it does not revive expired platform patents. [6]

What manufacturing and IP barriers remain?

The expired patent does not remove the practical barriers to commercial development. The principal manufacturing issues include:

Controlling polymer molecular weight and inherent viscosity;
Reproducing glycolide-to-lactide ratios;
Protecting peptides from organic-solvent and shear exposure;
Controlling particle-size distribution;
Limiting burst release;
Achieving a consistent degradation profile;
Removing residual solvent;
Maintaining sterility;
Preventing aggregation and chemical modification of the peptide; and
Establishing in vitro-in vivo release correlation.

Later patent claims may focus on these parameters because they are closer to commercial product differentiation than the broad platform concepts in US 4,767,628.

What litigation or settlement issues affect the patent?

No current litigation or settlement can preserve enforceability after expiration. Any historical dispute involving US 4,767,628 would have commercial relevance only for prior damages, license interpretation, prosecution history, or prior-art analysis.

A current competitor would instead review:

Continuations and divisionals;
Foreign family members;
Later patents owned by the original assignee or licensees;
Patents covering the same peptide depot;
Orange Book-listed patents for the reference product;
Paragraph IV litigation involving later product patents; and
Any license or settlement agreements governing later patent families.

The supplied claim set does not identify the assignee, inventors, priority application, continuation chain, or licensees. Those facts cannot be reliably inferred from the claims alone.

Key Takeaways

US 4,767,628 covers biodegradable polylactide or PLGA matrices containing pharmacologically active polypeptides.
Claim 1 requires overlapping diffusion-controlled and degradation-induced release phases.
Claims 2 through 17 narrow the invention by peptide identity, molecular weight, polymer viscosity, glycolide content, loading, and injectable suspension format.
The patent was granted August 30, 1988, and ordinarily expired August 30, 2005.
It presents no current United States infringement, Orange Book, or Paragraph IV barrier.
The patent remains relevant as prior art against later PLGA peptide-delivery patents.
Current freedom-to-operate risk will usually arise from later formulation, process, device, method-of-use, and product-specific patents.
Biosimilar risk is indirect because the claims focus on a delivery platform rather than a specific biologic molecule.
The most important technical evidence concerns polymer composition, inherent viscosity, uniform peptide dispersion, particle characteristics, and overlapping release phases.

FAQs About US Patent 4,767,628

Does US 4,767,628 cover all PLGA peptide formulations?

No. It covers formulations meeting the specified polymer, viscosity, peptide, dispersion, and release-profile limitations. A PLGA formulation outside those limitations would not necessarily infringe.

Can an expired PLGA patent block FDA approval?

No. An expired patent cannot block FDA approval through patent enforcement. FDA approval may still require addressing product-specific patents, regulatory exclusivity, safety, efficacy, and manufacturing requirements.

Is claim 17 limited to microspheres?

No express microsphere limitation appears in the supplied language. Claim 17 requires a fine-particle solid formulation suspended in an injectable liquid carrier. Microspheres may fall within the claim, but the claim is not expressly limited to spherical particles.

Are the listed peptides in claim 2 exhaustive?

Claim 2 lists specific peptide substances and analogues. Claim 1 is broader and is not limited to the listed compounds, provided the composition satisfies the general polypeptide and release limitations.

Can later PLGA patents still be enforced against a generic applicant?

Yes. Expiration of US 4,767,628 does not eliminate later patent rights. A generic applicant must conduct a separate analysis of active patents covering the reference product, formulation, manufacturing method, delivery device, and approved use.

References

United States Patent and Trademark Office. (1988). United States Patent No. 4,767,628.
United States Patent and Trademark Office. (n.d.). Patent term calculator and patent term resources.
35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Refuse-to-receive standards.
U.S. Food and Drug Administration. (2025). Purple Book: Database of licensed biological products.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8104734	Feb 16, 1981

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	22535	⤷ Start Trial
Australia	2840789	⤷ Start Trial
Australia	560829	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,767,628

Summary for Patent: 4,767,628