United States Patent 5,023,082 (US5023082): Scope of Claims and U.S. Patent Landscape for Liquid-Precursor Biodegradable Sustained-Release Protein Matrices
US 5,023,082 claims a platform for forming a biodegradable sustained-release matrix by administering a liquid precursor that solidifies in situ. The matrix is formed by cross-linking a water-soluble protein into a water-insoluble polymeric structure, with a plasticizer and a cross-linking agent governing mechanical properties and release behavior.
What is the core claim scope of US5023082?
Claim architecture
The independent claims define three functional blocks:
1) A liquid precursor composition that is administered and then solidifies into a biodegradable sustained-release composition.
2) The solidified matrix is built from cross-linked, water-insoluble protein (cross-linked from a water-soluble protein).
3) A plasticizing agent and a cross-linking agent are included to control brittleness/structural stability and cross-link density.
Independent claims (as provided):
- Claim 1: Liquid precursor composition for in situ solidification into biodegradable sustained-release composition.
- Claim 2: The resulting biodegradable sustained-release composition (composition-only).
- Claim 3: Method of administration using the liquid precursor that solidifies after administration.
- Claim 10: Method for administration of the biodegradable sustained-release composition.
Key structural/functional elements (common to Claims 1/2/3/10)
A. Plasticizing agent (broad class)
Plasticizer is selected from: phthalate ester, phosphate ester, glycol derivative, hydrocarbon, oil, fatty acid.
This is a wide category that is not restricted to a single polymer chemistry.
B. Active agent (broad functional dosing)
Active agent is present “in an amount sufficient to impart a desired therapeutic, agricultural, or catalytic property.”
“Therapeutic” triggers pharmaceutical use, but the claim text also supports non-medical uses (agricultural/catalytic).
C. Cross-linking agent (broad and heterogeneous list)
Cross-linking agent is selected from:
aldehydes, alcohols, aluminum, chromium, titanium, zirconium, an acyl chloride, bis-diazobenzidine, phenol-2,4-disulfonyl chloride, 1,5-difluoro-2,4-dinitrobenzene, urea, 3,6-bis(mercurimethyl)-dioxane urea, dimethyl adipimidate, N,N’-ethylene-bis-iodacetamide.
This is broad across chemical classes:
- protein-reactive cross-linkers (e.g., aldehydes such as formaldehyde/glutaraldehyde)
- carbonyl/chloride/sulfonyl electrophiles (e.g., acyl chloride, phenol-2,4-disulfonyl chloride)
- azo/diazonium-type crosslinking agents (bis-diazobenzidine)
- metal ions (aluminum, chromium, titanium, zirconium)
- amidination-type (dimethyl adipimidate)
- alkylation-type (ethylene-bis-iodacetamide)
- urea-based reagents (including the cited mercury-containing crosslinking reagent)
D. Water-soluble protein converted into a water-insoluble biodegradable polymeric matrix
Claim 1 and 2 require:
- A water-soluble protein capable of being cross-linked into a water-insoluble, biodegradable polymeric matrix.
- A concentration window balancing:
- structural stability after cross-linking
- while not reaching levels that make the sustained-release composition:
- incapable of biodegradation, or
- incapable of permitting release of the active agent.
This is written as a functional concentration limitation rather than an explicit protein mass fraction alone (though dependent claims supply ranges).
Distinctive “liquid precursor” vs “formed composition”
The differentiator in Claim 1/3 is the liquid precursor that solidifies to form the matrix after administration. Claim 2/10 cover the finished composition.
This structure matters for infringement theory:
- products sold as pre-formed solids may align more with Claim 2/10
- injectables, instillates, or in situ forming gels align more with Claim 1/3
How narrow are the dependent claims, and what do they add to enforceable scope?
Dependent claims define specific sub-ranges, preferred chemistries, geometry, proteins, and end-use administration modalities. They do not rewrite the platform; they narrow it.
Cross-linker amount and specific cross-linkers
- Claim 4: Cross-linking agent amount sufficient to render protein insoluble but not so much that it prevents release.
- Claim 5: Cross-linking agent present at ~0.01% to ~26%.
- Claims 6-7: If aldehyde cross-linker is used, it is formaldehyde or glutaraldehyde; glutaraldehyde is a dependent preferred example.
Impact: Claim 5 gives a numeric cap/floor for cross-linker content, supporting claim construction and product mapping for formulation dossiers.
Cross-linking means
- Claim 8: protein cross-linked by incubation with cross-linking means selected from heat, pressure, radiation, or vapors of cross-linking agent.
- Claim 9: extent is sufficient to render protein insoluble but not to prevent release.
Protein identity and concentration ranges
- Claim 11: protein selected from gelatin, collagen, albumin, enzyme, fibrinogen.
- Claim 12: gelatin preferred.
- Claim 13: gelatin is hydrolyzed gelatin.
- Claim 14: protein concentration ~14% to ~93%.
Impact: Claim 11 narrows the platform to common biopolymer proteins; Claim 14 gives a very high mass-fraction range, typical of protein-based hydrogels/films.
Plasticizer identity, concentration, and mechanical tuning
- Claim 15: plasticizer amount effects brittleness but does not prevent release.
- Claim 16: plasticizer is a glycol derivative.
- Claim 17: glycol derivative is glycerin or sorbitol; glycerin preferred via Claim 18.
- Claim 19: plasticizer concentration ~0.01% to ~52%.
Active agent category expansion
- Claim 20: active agent is a pharmacological agent.
- Claim 21: examples include broad drug classes (analgesic, anti-arrhythmic, anti-bacterial, antibiotic, antiviral, anti-convulsant, anti-fungal, anti-pyretic, anti-inflammatory, anti-tumor, anti-ulcer, cardiovascular, diuretic, hormone, hypoglycemic, hypotensive, ophthalmological, sedative, hypnotic, tranquilizer).
- Claims 22-24: antibacterial agent examples include penicillin, cephalosporin, tetracycline family, metronidazole, chloramphenicol, streptomycin, neomycin, sulfonamides, phenolic compounds, mercurials, quaternary ammonium compounds, chlorhexidine; with chlorhexidine as a dependent preference.
- Claims 25-26: supports combinations and even “all agents selected from the same group of therapeutic agents.”
Impact: these claims support both single-drug and multi-drug antibacterial/therapeutic formulations, with chlorhexidine explicitly anchored.
Film format and dimensions
- Claim 27: sustained-release composition “substantially a two-dimensional film.”
- Claim 28: dimensions:
- length ~3 to ~10 mm
- width ~1 to ~5 mm
- depth ~0.01 to ~0.5 mm
Flexibility metric
- Claim 31: flexibility ~0.1 kg/mm² to ~50 kg/mm².
Relative weight ratios
- Claim 29: pharmacological agent : protein ~0.01:7 to ~3:1
- Claim 30: plasticizing agent : protein ~0.01:7 to ~4:7
These ratios convert platform language into formulation math for product design and design-around.
What end-use/route restrictions appear in the claims?
Administration routes (dependent)
- Claim 32: administration by intra-nasal, intra-ocular, intra-aural, subcutaneous, transdermal, topical, and parenteral means.
Implant forms and dental-specific use
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Claims 33-34: implant includes gingival crevice implant, vaginal implant, testicular implant; plus a specific dependent selection for gingival crevice implant.
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Claims 35-38: treatment method:
- provides the composition containing a pharmacological agent with therapeutic effect (Claim 35)
- implant into periodontal pocket (Claim 36)
- antibacterial agent (Claim 37)
- condition can be periodontal disease (Claim 38) with antibacterial effectiveness.
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Claims 39-42 expand condition/procedure scope:
- pericoronitis (Claim 39)
- adjunct to endodontic treatment (Claim 40)
- adjunct to tooth implantation procedure (Claim 41)
- adjunct to epiectomy (Claim 42)
Impact: The dental/periodontal family is explicit. The medical use is not limited to systemic administration; it includes local implants and procedure adjuncts.
How does this scope translate into a patent landscape view?
A meaningful landscape analysis requires knowing (a) who else claimed similar protein-based in situ forming sustained release systems and (b) the priority dates and assignees for those documents, plus (c) prosecution history for US5023082. Those data are not present in the prompt.
Given only the claim text, the only defensible landscape statements are structural: what technical design choices will fall inside or outside US5023082 based on claim elements.
Likely “in-scope” formulation patterns (by claim element match)
US5023082 is most directly implicated by products that satisfy all of the following simultaneously:
1) In situ solidification from a liquid precursor that forms a sustained-release matrix in the body. (Claims 1 and 3)
2) The matrix is cross-linked water-insoluble protein, where the protein begins water-soluble and becomes insoluble via cross-linking. (Claims 1/2/10)
3) The formulation includes:
- a plasticizing agent in one of the enumerated classes (phthalate/phosphate/glycol/hydrocarbon/oil/fatty acid) (Claims 1/2/3/10)
- a cross-linker enumerated in the claim list (including aldehydes like glutaraldehyde). (Claims 1/2/3/10, plus dependent refinements)
4) The composition is engineered so cross-link density provides structural stability but still allows biodegradation and active release. (Claims 1/2/4/9)
If a product instead uses:
- a synthetic polymer matrix (non-protein)
- cross-linkers not in the enumerated set (depending on interpretation)
- no plasticizer (or a plasticizer outside listed classes)
- no in situ liquid precursor solidification
then it moves toward design-around territory.
Likely “out-of-scope” patterns (based on element failure)
From a literal-claim mapping perspective:
- If the matrix is not protein-derived (no “cross-linked, water-insoluble protein”), it fails a central limitation in Claims 1/2/10.
- If the composition is already pre-formed and does not rely on a liquid precursor solidifying after administration, it is less aligned with Claims 1/3 (but could still target Claim 2/10 if the finished composition matches).
- If cross-linking agents are outside the provided list, that is a literal mismatch for Claims 1/2/3/10 (again, depending on doctrine of equivalents not analyzed here).
What is the enforceable “center of gravity” for freedom-to-operate?
The dominant claim “gravity” is the protein-cross-linking platform plus in situ or formed sustained release, with a broad set of selectable:
- plasticizers
- cross-linking agents
- proteins
- active agents
- administration routes and dental implant use
The dependent claims add specificity that can catch specific commercial formulations:
- glutaraldehyde cross-linking
- gelatin/hydrolyzed gelatin
- glycerin or sorbitol plasticizers
- explicit cross-linker % (0.01 to 26%)
- protein % (14 to 93%)
- film dimensions
- flexibility metric
- chlorhexidine as antibacterial example
- periodontal pocket/gingival crevice implants and dental procedure adjuncts
Key design parameters embedded in the claim text
These are the knobs most likely to appear in formulation dossiers and thus most likely to be used in claim charting:
- Cross-linker identity: includes aldehydes and many electrophiles/metal ions.
- Cross-linker loading: 0.01% to 26%.
- Cross-linking extent: insolubilize protein but do not block release or biodegradation.
- Plasticizer class: phthalate/phosphate/glycol/hydrocarbon/oil/fatty acid.
- Plasticizer loading: 0.01% to 52% (when tied to dependent plasticizer embodiments).
- Protein identity: gelatin, collagen, albumin, enzyme, fibrinogen; hydrolyzed gelatin preferred in dependent claims.
- Protein loading: 14% to 93% (dependent).
- Geometry: optionally a two-dimensional film with specified dimensions.
- Mechanical property: flexibility 0.1 to 50 kg/mm² (dependent).
- Use pattern: periodontal pocket / gingival crevice implant, plus periodontal disease and pericoronitis, adjunct to endodontic/tooth implantation/epiectomy.
Key Takeaways
- US5023082 claims an in situ formed biodegradable sustained-release matrix made by cross-linking a water-soluble protein into a water-insoluble, biodegradable polymeric structure, using a selected plasticizer and enumerated cross-linking agents.
- The platform is broad on active agents and administration routes, and it is explicitly broad on protein-cross-linking chemistries, but narrow on core matrix origin (cross-linked protein) and enumerated cross-linking-agent classes.
- Dependent claims lock in commercially actionable formulation specifics: glutaraldehyde, gelatin/hydrolyzed gelatin, glycerin/sorbitol, cross-linker 0.01-26%, protein 14-93%, plus dental implant use and chlorhexidine as an antibacterial example.
- For freedom-to-operate, the decisive element is whether a product matches the claim’s protein cross-linking matrix formation plus liquid precursor solidification (Claims 1/3) and whether its cross-linker and plasticizer fall within the enumerated sets.
FAQs
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Is US5023082 limited to medical use?
No. The active agent is required to impart therapeutic, agricultural, or catalytic properties (Claims 1/2/3/10).
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Does infringement require that the cross-linker be an aldehyde?
No. Aldehydes are one option; the claim lists many cross-linker types (Claims 1/2/3/10). Dependent claims narrow to formaldehyde/glutaraldehyde.
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What is the central technical limitation: is it the plasticizer or the protein matrix?
The protein matrix. Claims require a cross-linked water-insoluble protein biodegradable polymeric matrix; the plasticizer is also required but the protein-derived matrix is the core structure (Claims 1/2/10).
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Does the claim cover both a liquid precursor and a final solid composition?
Yes. Claim 1/3 cover liquid precursor solidifying in situ; Claim 2/10 cover the biodegradable sustained-release composition.
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Are dental applications explicitly claimed?
Yes. Dependent method claims include implants into gingival crevice/periodontal pocket and treatment of periodontal disease and pericoronitis, including adjuncts to endodontic/tooth implantation/epiectomy (Claims 33-42).
References
[1] United States Patent 5,023,082. (Claim text provided in prompt).
