Scope and Claims Review: US Patent 5,366,734 (Method for Continuous Delivery of Peptides Using Polylactide Implants)

US 5,366,734 is a combination product-method claim centered on a specific peptide dose form (polylactide matrix) and a specific release mechanism requirement (overlapping diffusion and degradation phases) that is further constrained by continuous, non-biphasic release for at least one week. The operative claim is drafted as a “method of continuous administration” that is inseparable from the composition’s construction and release kinetics. Practically, the infringement surface is narrow but deep: to avoid infringement, a challenger must change one of the hard technical anchors (polymer chemistry/grade, peptide characterization, matrix water-domain behavior, and overlap of diffusion and degradation release timing).

What does US 5,366,734 claim and what does it require for infringement?

Featured snippet answer: The patent claims a method of continuously administering a pharmaceutically active peptide by implanting or injecting a polylactide-based composition containing a defined peptide fraction dispersed to create surface-accessible peptide, where water uptake forms communicating aqueous peptide domains that trigger initial diffusion release overlapping in time with degradation-triggered release, producing continuous release for at least one week without biphasic discontinuity.

Claim 1 is composition-and-physics-linked

Claim 1 is structured as a three-step method:

Providing a particular implantable or injectable composition
Implanting or injecting to cause release via leaching and water absorption
Permitting continuous release for at least one week, with a specific release profile rule

This makes infringement dependent on both:

Whether the formulation matches every polymer and peptide parameter, and
Whether the release behavior matches the required overlapping diffusion and degradation phases and “not biphasic or discontinuous” outcome.

Core limitation set (the “must-haves”)

The claim’s technical anchors are the following, in descending order of practical impact on claim coverage:

A. Polymer matrix identity and grade

“From 50% to 99.999% polylactide”
Polylactide is restricted to:
- polylactide made from lactic acid alone, or
- PLA copolymer with glycolic acid where the glycolide:lactide ratio is 0 up to 3:1, or mixtures of these
Lactic acid can be racemic or optically active
Additional constraints on polymer “grade” via inherent viscosity bounds, which are explicitly tied to whether the polylactide is benzene-soluble or benzene-insoluble:
- If soluble in benzene: inherent viscosity 0.093–0.5 (as defined in the claim test conditions)
- If insoluble in benzene: inherent viscosity 0.093–4 (as defined)

B. Peptide identity and concentration

peptide (active polypeptide) is 0.001% to 50%
peptide molecular weight:
- “at least about the same as the molecular weight of tetragastrin”
peptide has:
- “four or more amino acid residues”
- not significantly hydrolyzed under conditions within the composition during intended use
peptide dispersion rule:
- dispersed in the polylactide such that “some of the polypeptide is present at the external surface of the composition”

C. Release mechanism: overlapping diffusion and degradation phases The composition “when placed in an aqueous physiological-type environment absorbs water and exhibits two successive phases,” but the claim then requires a critical characterization:

There are:
1. an initial diffusion phase (release by initial diffusion through aqueous peptide domains communicating with the exterior surface), and
2. a second phase (release consequent upon degradation of polylactide)
Key timing constraint: “diffusion phase and degradation-induced phase overlap in time”
The domain physics is spelled out:
- Water diffuses into the matrix
- Water partitions between polypeptide and polylactide to form aqueous polypeptide domains
- Domains increase with absorption until “continuity of the domains reaches a sufficient level to communicate with the exterior surface”
- Then peptide starts to be released by diffusion through aqueous polypeptide channels formed from the domains
- The “second phase continues until substantially all remaining polypeptide is released” over at least a week

D. Endpoint release profile rule: continuous and not biphasic/discontinuous In step (3) the method requires:

release proceeds continuously over at least one week
“release is not biphasic or discontinuous”

How this claim structure narrows infringement

This is not a generic “PLA implant releases peptide slowly” patent. It is a specific “release profile and mechanism” patent with:

specific polymer class + inherent viscosity range tied to solubility,
peptide molecular weight and stability constraints,
peptide surface accessibility,
explicit aqueous domain formation and channel formation,
overlap of diffusion and degradation phases,
and continuous release for at least one week without biphasic discontinuity.

A product that uses a broader polyester (e.g., PLGA with different ratios, different viscosity grades), different peptide stabilization, or releases with a clearly separated burst-diffusion then later degradation step may not meet the overlap and “not biphasic” requirements.

Which peptide drug types are covered by US 5,366,734?

Featured snippet answer: Any pharmaceutically active peptide meeting the claim constraints: at least tetragastrin-level molecular weight, at least four amino acids, and sufficiently resistant to hydrolysis during the intended use period, formulated as 0.001% to 50% dispersed within a defined polylactide matrix with peptide present at the external surface.

The claim is peptide-generic but with functional filters

The claim does not name a single drug. It uses tetragastrin as a molecular weight anchor. That tends to capture:

regulatory peptide/protein fragments around mid-size peptide mass,
peptide hormones and peptide therapeutics with >3 amino acids (the claim says ≥4 residues),
peptide drugs stabilized against hydrolysis in PLA matrix conditions.

Boundary conditions that can avoid coverage

If the peptide is below the tetragastrin molecular weight “at least about” threshold, it can fall outside claim 1.
If peptide hydrolysis is significant under composition conditions, the claim excludes it.
If the manufacturing approach does not place some peptide at the external surface, it can miss a required structural condition.
If release kinetics are clearly separated (a distinct early diffusion burst followed by later degradation-only release) the “overlap in time” and “not biphasic” constraints become harder to meet.

What polylactide formulations are required, and how do inherent viscosity and solubility matter?

Featured snippet answer: Claim 1 limits the matrix to 50% to 99.999% polylactide that is either (i) soluble in benzene with inherent viscosity 0.093–0.5, or (ii) insoluble in benzene with inherent viscosity 0.093–4; and, if glycolic acid is included, the glycolide:lactide unit ratio is 0 up to 3:1.

Polymer chemistry scope

The matrix is restricted to:

homopolymer PLA (lactic acid polymer alone), or
copolymer PLA/ PGA with limited glycolide content (up to 3:1 glycolide-to-lactide units), or
mixtures of those polymer/copolymer combinations.

Molecular weight proxy via inherent viscosity

The inherent viscosity bounds are explicitly defined as test-condition dependent measurements, which can become a practical litigation lever. A competitor can:

select polymer grades outside those viscosity bands,
alter solubility behavior in benzene through polymer composition/architecture,
argue the intrinsic viscosity falls outside the cited ranges.

How does the “overlapping diffusion and degradation phases” requirement change the landscape?

Featured snippet answer: It converts the claim from a simple “two-stage release exists” formulation into a “two-stage sources overlap in time” release-profile formulation, coupled to an aqueous-domain continuity and channel-formation mechanism.

Claim’s mechanistic release theory

The claim ties release behavior to:

formation of aqueous peptide domains through water partitioning between peptide and polylactide,
growth of domains until a continuous network communicates with exterior surface,
onset of diffusion release through peptide channels,
simultaneous contribution from degradation-triggered release that overlaps with the diffusion contribution.

Litigation implications

This mechanistic overlap is the type of limitation that can be tested with:

in vitro release curves resolved over time,
modeling of release contributions,
degradation kinetics correlation to release rate,
microstructural or imaging evidence of water domain/channel formation (depending on assay availability).

In practice, to clear a design-around, a challenger often aims for either:

a strongly separated diffusion early phase followed by a later degradation-only release phase, or
a release profile that remains clearly continuous but lacks the defined overlap signature (depending on how overlap is proven).

When does US 5,366,734 expire and what is the enforcement timeline?

No answer provided. The user-provided content contains claim text only, not filing date, publication date, prosecution history, or maintenance status. Without those, a complete and accurate exclusivity/expiration timeline cannot be produced.

What competitive landscape risk does US 5,366,734 create for peptide depot injectables?

Featured snippet answer: The risk centers on peptide depots using PLA/PLA-GA matrices where formulations are engineered to produce overlapping diffusion and degradation release for at least one week without biphasic discontinuity, with peptide dispersed including peptide at the external surface and meeting peptide size/stability constraints.

High-risk product design patterns

PLA or PLA/PGA peptide depots (including injectable microspheres, implants, or matrices) aimed at continuous release rather than “burst then slow” kinetics.
Formulations with peptide surface accessibility at manufacture or after formation that ensures initial diffusion through water-swollen peptide domains.
Ranges of peptide loading within 0.001% to 50%.

Lower-risk design patterns

Depots built for separated kinetics: distinct early diffusion phase followed by degradation-driven release later (clear biphasic pattern).
Use of polymer systems outside the constrained inherent viscosity/benzene-solubility-defined PLA grades.
Peptides engineered or selected to be hydrolysis-sensitive under matrix conditions (which can support non-infringement by exclusion from the “not significantly hydrolyzed” requirement, though litigation will treat this as technical and fact intensive).

Which patents could be implicated alongside US 5,366,734 (continuations, improvements, and family members)?

No answer provided. The user request is for landscape analysis, but the prompt does not include:

the patent family information,
related US applications/publications,
cited references,
or other jurisdictional equivalents. Without those, a complete landscape cannot be compiled while staying accurate.

What are the strongest “claim construction” leverage points in US 5,366,734?

Featured snippet answer: The most leverageable elements are (1) polymer grade constraints tied to inherent viscosity and benzene solubility, (2) the peptide dispersion requirement ensuring peptide at the external surface, and (3) the overlapping diffusion and degradation release time signature plus “not biphasic/discontinuous” endpoint over at least one week.

Construction targets likely to be contested

“consisting essentially of” and the scope of permitted components outside polylactide and peptide
“polylactide which is either soluble in benzene… or insoluble in benzene” as an objective characterization
inherent viscosity test method alignment
“some… present at the external surface” and how surface fraction is measured
“not significantly hydrolyzed under conditions encountered within the composition during the period of use envisioned”
proving overlap “in time” and the operational meaning of “not biphasic or discontinuous”

Key Takeaways

US 5,366,734 is a release-mechanism-driven method-of-use claim anchored to a specific polylactide matrix (PLA/limited PLA-GA) with defined inherent viscosity ranges tied to benzene solubility.
Coverage is limited to peptides meeting molecular weight (tetragastrin anchor), ≥4 residues, and hydrolysis resistance constraints, loaded 0.001% to 50%, dispersed so that some peptide is on the external surface.
Infringement hinges on demonstrating water-uptake domain formation that creates diffusion channels, with diffusion and degradation-driven release overlapping in time, producing continuous release for at least one week with no biphasic or discontinuous profile.
Design-around strategy typically targets one or more hard requirements: polymer grade, peptide stability/size, peptide surface accessibility, or the release profile’s overlap/biphasic character.

FAQs

Does US 5,366,734 cover PLA implants for any peptide as long as release is slow?
How would a competitor prove non-infringement if their release curve looks continuous but two mechanistic phases appear?
What manufacturing changes affect the “peptide present at the external surface” limitation most directly?
How do benzene solubility and inherent viscosity constraints function as objective switches for claim scope?
Can peptide hydrolysis sensitivity be used as a technical basis to avoid the “not significantly hydrolyzed” limitation?

References

United States Patent 5,366,734. Method for continuously administering a pharmaceutically active peptide to a subject using a polylactide composition with overlapping diffusion and degradation release.

Title:	Continuous release pharmaceutical compositions
Abstract:	Pharmaceutical compositions, comprising a polylactide and a pharmacologically active, acid stable polypeptide, which when placed in an aqueous physiological environment release the polypeptide at an approximately constant rate in an essentially monophasic manner, with a minimal, or no induction period prior to the release; polylactides suitable for use in said compositions; and a method for the manufacture of such polylactides.
Inventor(s):	Francis G. Hutchinson
Assignee:	AstraZeneca UK Ltd , Syngenta Ltd
Application Number:	US07/751,584
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;
Patent landscape, scope, and claims:	Scope and Claims Review: US Patent 5,366,734 (Method for Continuous Delivery of Peptides Using Polylactide Implants) US 5,366,734 is a combination product-method claim centered on a specific peptide dose form (polylactide matrix) and a specific release mechanism requirement (overlapping diffusion and degradation phases) that is further constrained by continuous, non-biphasic release for at least one week. The operative claim is drafted as a “method of continuous administration” that is inseparable from the composition’s construction and release kinetics. Practically, the infringement surface is narrow but deep: to avoid infringement, a challenger must change one of the hard technical anchors (polymer chemistry/grade, peptide characterization, matrix water-domain behavior, and overlap of diffusion and degradation release timing). What does US 5,366,734 claim and what does it require for infringement? Featured snippet answer: The patent claims a method of continuously administering a pharmaceutically active peptide by implanting or injecting a polylactide-based composition containing a defined peptide fraction dispersed to create surface-accessible peptide, where water uptake forms communicating aqueous peptide domains that trigger initial diffusion release overlapping in time with degradation-triggered release, producing continuous release for at least one week without biphasic discontinuity. Claim 1 is composition-and-physics-linked Claim 1 is structured as a three-step method: Providing a particular implantable or injectable composition Implanting or injecting to cause release via leaching and water absorption Permitting continuous release for at least one week, with a specific release profile rule This makes infringement dependent on both: Whether the formulation matches every polymer and peptide parameter, and Whether the release behavior matches the required overlapping diffusion and degradation phases and “not biphasic or discontinuous” outcome. Core limitation set (the “must-haves”) The claim’s technical anchors are the following, in descending order of practical impact on claim coverage: A. Polymer matrix identity and grade “From 50% to 99.999% polylactide” Polylactide is restricted to: polylactide made from lactic acid alone, or PLA copolymer with glycolic acid where the glycolide:lactide ratio is 0 up to 3:1, or mixtures of these Lactic acid can be racemic or optically active Additional constraints on polymer “grade” via inherent viscosity bounds, which are explicitly tied to whether the polylactide is benzene-soluble or benzene-insoluble: If soluble in benzene: inherent viscosity 0.093–0.5 (as defined in the claim test conditions) If insoluble in benzene: inherent viscosity 0.093–4 (as defined) B. Peptide identity and concentration peptide (active polypeptide) is 0.001% to 50% peptide molecular weight: “at least about the same as the molecular weight of tetragastrin” peptide has: “four or more amino acid residues” not significantly hydrolyzed under conditions within the composition during intended use peptide dispersion rule: dispersed in the polylactide such that “some of the polypeptide is present at the external surface of the composition” C. Release mechanism: overlapping diffusion and degradation phases The composition “when placed in an aqueous physiological-type environment absorbs water and exhibits two successive phases,” but the claim then requires a critical characterization: There are: an initial diffusion phase (release by initial diffusion through aqueous peptide domains communicating with the exterior surface), and a second phase (release consequent upon degradation of polylactide) Key timing constraint: “diffusion phase and degradation-induced phase overlap in time” The domain physics is spelled out: Water diffuses into the matrix Water partitions between polypeptide and polylactide to form aqueous polypeptide domains Domains increase with absorption until “continuity of the domains reaches a sufficient level to communicate with the exterior surface” Then peptide starts to be released by diffusion through aqueous polypeptide channels formed from the domains The “second phase continues until substantially all remaining polypeptide is released” over at least a week D. Endpoint release profile rule: continuous and not biphasic/discontinuous In step (3) the method requires: release proceeds continuously over at least one week “release is not biphasic or discontinuous” How this claim structure narrows infringement This is not a generic “PLA implant releases peptide slowly” patent. It is a specific “release profile and mechanism” patent with: specific polymer class + inherent viscosity range tied to solubility, peptide molecular weight and stability constraints, peptide surface accessibility, explicit aqueous domain formation and channel formation, overlap of diffusion and degradation phases, and continuous release for at least one week without biphasic discontinuity. A product that uses a broader polyester (e.g., PLGA with different ratios, different viscosity grades), different peptide stabilization, or releases with a clearly separated burst-diffusion then later degradation step may not meet the overlap and “not biphasic” requirements. Which peptide drug types are covered by US 5,366,734? Featured snippet answer: Any pharmaceutically active peptide meeting the claim constraints: at least tetragastrin-level molecular weight, at least four amino acids, and sufficiently resistant to hydrolysis during the intended use period, formulated as 0.001% to 50% dispersed within a defined polylactide matrix with peptide present at the external surface. The claim is peptide-generic but with functional filters The claim does not name a single drug. It uses tetragastrin as a molecular weight anchor. That tends to capture: regulatory peptide/protein fragments around mid-size peptide mass, peptide hormones and peptide therapeutics with >3 amino acids (the claim says ≥4 residues), peptide drugs stabilized against hydrolysis in PLA matrix conditions. Boundary conditions that can avoid coverage If the peptide is below the tetragastrin molecular weight “at least about” threshold, it can fall outside claim 1. If peptide hydrolysis is significant under composition conditions, the claim excludes it. If the manufacturing approach does not place some peptide at the external surface, it can miss a required structural condition. If release kinetics are clearly separated (a distinct early diffusion burst followed by later degradation-only release) the “overlap in time” and “not biphasic” constraints become harder to meet. What polylactide formulations are required, and how do inherent viscosity and solubility matter? Featured snippet answer: Claim 1 limits the matrix to 50% to 99.999% polylactide that is either (i) soluble in benzene with inherent viscosity 0.093–0.5, or (ii) insoluble in benzene with inherent viscosity 0.093–4; and, if glycolic acid is included, the glycolide:lactide unit ratio is 0 up to 3:1. Polymer chemistry scope The matrix is restricted to: homopolymer PLA (lactic acid polymer alone), or copolymer PLA/ PGA with limited glycolide content (up to 3:1 glycolide-to-lactide units), or mixtures of those polymer/copolymer combinations. Molecular weight proxy via inherent viscosity The inherent viscosity bounds are explicitly defined as test-condition dependent measurements, which can become a practical litigation lever. A competitor can: select polymer grades outside those viscosity bands, alter solubility behavior in benzene through polymer composition/architecture, argue the intrinsic viscosity falls outside the cited ranges. How does the “overlapping diffusion and degradation phases” requirement change the landscape? Featured snippet answer: It converts the claim from a simple “two-stage release exists” formulation into a “two-stage sources overlap in time” release-profile formulation, coupled to an aqueous-domain continuity and channel-formation mechanism. Claim’s mechanistic release theory The claim ties release behavior to: formation of aqueous peptide domains through water partitioning between peptide and polylactide, growth of domains until a continuous network communicates with exterior surface, onset of diffusion release through peptide channels, simultaneous contribution from degradation-triggered release that overlaps with the diffusion contribution. Litigation implications This mechanistic overlap is the type of limitation that can be tested with: in vitro release curves resolved over time, modeling of release contributions, degradation kinetics correlation to release rate, microstructural or imaging evidence of water domain/channel formation (depending on assay availability). In practice, to clear a design-around, a challenger often aims for either: a strongly separated diffusion early phase followed by a later degradation-only release phase, or a release profile that remains clearly continuous but lacks the defined overlap signature (depending on how overlap is proven). When does US 5,366,734 expire and what is the enforcement timeline? No answer provided. The user-provided content contains claim text only, not filing date, publication date, prosecution history, or maintenance status. Without those, a complete and accurate exclusivity/expiration timeline cannot be produced. What competitive landscape risk does US 5,366,734 create for peptide depot injectables? Featured snippet answer: The risk centers on peptide depots using PLA/PLA-GA matrices where formulations are engineered to produce overlapping diffusion and degradation release for at least one week without biphasic discontinuity, with peptide dispersed including peptide at the external surface and meeting peptide size/stability constraints. High-risk product design patterns PLA or PLA/PGA peptide depots (including injectable microspheres, implants, or matrices) aimed at continuous release rather than “burst then slow” kinetics. Formulations with peptide surface accessibility at manufacture or after formation that ensures initial diffusion through water-swollen peptide domains. Ranges of peptide loading within 0.001% to 50%. Lower-risk design patterns Depots built for separated kinetics: distinct early diffusion phase followed by degradation-driven release later (clear biphasic pattern). Use of polymer systems outside the constrained inherent viscosity/benzene-solubility-defined PLA grades. Peptides engineered or selected to be hydrolysis-sensitive under matrix conditions (which can support non-infringement by exclusion from the “not significantly hydrolyzed” requirement, though litigation will treat this as technical and fact intensive). Which patents could be implicated alongside US 5,366,734 (continuations, improvements, and family members)? No answer provided. The user request is for landscape analysis, but the prompt does not include: the patent family information, related US applications/publications, cited references, or other jurisdictional equivalents. Without those, a complete landscape cannot be compiled while staying accurate. What are the strongest “claim construction” leverage points in US 5,366,734? Featured snippet answer: The most leverageable elements are (1) polymer grade constraints tied to inherent viscosity and benzene solubility, (2) the peptide dispersion requirement ensuring peptide at the external surface, and (3) the overlapping diffusion and degradation release time signature plus “not biphasic/discontinuous” endpoint over at least one week. Construction targets likely to be contested “consisting essentially of” and the scope of permitted components outside polylactide and peptide “polylactide which is either soluble in benzene… or insoluble in benzene” as an objective characterization inherent viscosity test method alignment “some… present at the external surface” and how surface fraction is measured “not significantly hydrolyzed under conditions encountered within the composition during the period of use envisioned” proving overlap “in time” and the operational meaning of “not biphasic or discontinuous” Key Takeaways US 5,366,734 is a release-mechanism-driven method-of-use claim anchored to a specific polylactide matrix (PLA/limited PLA-GA) with defined inherent viscosity ranges tied to benzene solubility. Coverage is limited to peptides meeting molecular weight (tetragastrin anchor), ≥4 residues, and hydrolysis resistance constraints, loaded 0.001% to 50%, dispersed so that some peptide is on the external surface. Infringement hinges on demonstrating water-uptake domain formation that creates diffusion channels, with diffusion and degradation-driven release overlapping in time, producing continuous release for at least one week with no biphasic or discontinuous profile. Design-around strategy typically targets one or more hard requirements: polymer grade, peptide stability/size, peptide surface accessibility, or the release profile’s overlap/biphasic character. FAQs Does US 5,366,734 cover PLA implants for any peptide as long as release is slow? How would a competitor prove non-infringement if their release curve looks continuous but two mechanistic phases appear? What manufacturing changes affect the “peptide present at the external surface” limitation most directly? How do benzene solubility and inherent viscosity constraints function as objective switches for claim scope? Can peptide hydrolysis sensitivity be used as a technical basis to avoid the “not significantly hydrolyzed” limitation? References United States Patent 5,366,734. Method for continuously administering a pharmaceutically active peptide to a subject using a polylactide composition with overlapping diffusion and degradation release. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8014734	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
Australia	582920	⤷ Start Trial
Australia	602623	⤷ Start Trial
Australia	6498886	⤷ Start Trial
Australia	7998682	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,366,734

Summary for Patent: 5,366,734