Patent: 10,016,534

Summary for Patent: 10,016,534

Title:	Protein biomaterial and biocoacervate vessel graft systems and methods of making and using thereof
Abstract:	The present invention relates to protein biocoacervates and biomaterials vessel graft systems used in cardiovascular applications and other medical applications, the components utilized in the vessel graft systems and the methods of making and using such systems. More specifically the present invention relates to protein biocoacervates and biomaterials vessel graft systems used in various medical applications and/or the devices used in such vessel graft systems including, but not limited to, vessel grafts as drug delivery devices for the controlled release of pharmacologically active agents, tubular grafts, vascular grafts, protein biomaterial sutures and biomeshes, protein biomaterial adhesives and glues, and other biocompatible biocoacervate or biomaterial devices used in the vessel graft systems of the present invention.
Inventor(s):	Masters; David B. (Minneapolis, MN)
Assignee:	Gel-Del Technologies, Inc. (St. Paul, MN)
Application Number:	13/131,083
Patent Claims:	see list of patent claims

United States Patent 10,016,534 Claims and Patent Landscape Analysis for Vessel Graft Systems Using Precipitated Amorphous Thermoplastic Biocoacervates

US Patent 10,016,534 claims a vessel graft system in which (i) a tubular graft and (ii) end-sealing threads/sutures/wraps are formed using precipitated amorphous thermoplastic “biocoacervate” biomaterials made from solubilized primary proteins + glycosaminoglycans + biocompatible solvents, and (iii) a bioglue at the anastomosis site seals the threads/wraps using the same biocoacervate chemistry plus crosslinkers. Claim scope is broad on protein/glycosaminoglycan lists and active-agent classes, but it is narrowed by the requirement that the biomaterials are precipitated amorphous thermoplastic biocoacervates with a defined composition concept (protein + glycosaminoglycan + solvent), and by an explicit anastomosis-site sealing function tied to the bioglue.

Landscape note: A complete, jurisdiction-ready “patent landscape” (other assignee patents, family members, prosecution history, claim charted competitors, Orange Book/BPCIA ties, and litigation outcomes) cannot be generated from the claims alone. The analysis below is limited to claim construction risk, design-around vectors, enforceability pressure points, and what the claim language itself implies about overlapping patentability and infringement exposure.

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What does US Patent 10,016,534 claim for vessel graft systems using biocoacervate thermoplastic biomaterials? (Claim scope, elements, and functional limitations)

Independent claim 1 requires all of the following core elements:

1. A vessel graft system with:
   • One or more tubes having one or more components.
   • At least one component includes a first biomaterial made from one or more precipitated amorphous thermoplastic biocoacervate(s).
2. Biocoacervate definition is compositional:
   • The biocoacervate includes:
     • soluble or solubilized primary proteins
     • glycosaminoglycans
     • biocompatible solvents
   • And is formed into a tubular configuration (for the tube component).
3. End-region retention and sealing mechanism:
   • Threads, sutures and/or wraps positioned at one or more ends of the tube(s).
4. Pharmacologic delivery concept:
   • The threads/sutures/wraps comprise biomaterial made from the same precipitated amorphous thermoplastic biocoacervate chemistry and contain one or more pharmacologically active agents.
   • They deliver the active agent(s) to an anastomosis site.
5. Bioglue chemistry and function:
   • A bioglue is administered at the anastomosis site.
   • The bioglue comprises:
     • precipitated amorphous thermoplastic biocoacervate
     • one or more crosslinkers
   • The bioglue seals the threads/sutures/wraps at the anastomosis site.

Key claim-structure pressure points

• “Precipitated amorphous thermoplastic biocoacervate(s)” is the anchor limitation. If a product uses coacervate-like phases but they are not amorphous thermoplastic or not precipitated in the claimed sense, infringement arguments become harder.
• The claim ties multiple system parts (tube component, thread/wrap biomaterial, and bioglue) to the same technology concept. A design-around that replaces only one part may still avoid literal infringement depending on whether the omitted part is strictly required.

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How do the dependent claims narrow US 10,016,534? (Protein, GAG, solvent, additives, actives, and crosslinkers)

Material identity and architecture

• Claim 2: Tube biocoacervates and thread/wrap biocoacervates are the same material.
• Claim 3: Tube includes structural scaffolding coated or encapsulated with the thermoplastic biomaterial.
• Claim 15: Tube/thread biomaterial comprises collagen, heparin, elastin and water.

Protein scope

• Claim 4: Primary proteins can include collagen, laminin, BMP isoforms with GAG binding sites, albumin, interleukins, EGF family members, fibronectin, thrombin, aprotinin, antithrombin III.
• Claim 6: Tube can further include secondary proteins.
• Claim 7: Secondary proteins include fibrin/fibrinogen, elastin, albumin, ovalbumin, keratin, silk/silk fibroin, actin, myosin, thrombin, aprotinin, antithrombin III.

GAG scope

• Claim 5: Glycosaminoglycans include heparin/heparin sulfate, keratan sulfate, dermatin/dermatin sulfate, various heparin-hyaluronic acid and chondroitin sulfate forms, chitin/chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican, and complexes.

Solvent scope

• Claim 8: Biocompatible solvents include water, DMSO, biocompatible alcohols, acids, oils, glycols.

Active agents

• Claim 9: Broad class list: analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors/growth factors, steroids/steroid inhibitors, antiglaucoma/anti-alcohol/anti-coagulant/anti-thrombolytics, anticancer, anti-inflammatory, anticonception agents, enzymes, cells, growth factors, antivirals, antibacterial, antifungal, chemoattractants.
• Claim 10: Specific examples include paclitaxol, sirolimus, estradiol, dexamethasone, vitamin E/C, stem cells, superoxide dismutase, VEGF/FGF/EGF, cortisone.

Additives and polymer coatings

• Claim 11-12: Tube further includes biocompatible additives; lists include a wide range of epoxies, polyesters, acrylics, nylon, silicones, polyurethanes, fluoropolymers (PTFE), polycaprolactone, polyacrylates, polyanhydride, poly(ethylene) oxide/PEG, PVC, PLA/PGA, and extensive biomolecule/additive categories including many proteins and lipids.
  • This breadth increases infringement risk for many plausible “hybrid graft” designs.

Crosslinkers for the bioglue

• Claim 13-14: Biocoacervates crosslinked with crosslinking agents; examples include glutaraldehyde, 1,4-butanediol diglycidyl ether, formaldehyde, glyoxal, sebacic acid bis(N-succinimidyl) ester (DSS), azido-benzolyl hydrazide, multiple azido-nitro and NHS-azide reagents.

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Which infringement theories are most plausible under claim 1? (Literal infringement vs. doctrine-of-equivalents)

Literal infringement strongest when the system matches the biocoacervate definition across parts

To establish literal infringement of claim 1, an accused vessel graft system must show:

• Tube component includes precipitated amorphous thermoplastic biocoacervate made from soluble primary proteins + GAGs + biocompatible solvents.
• End threads/sutures/wraps include biomaterial from the same category and carry pharmacologically active agents delivered to the anastomosis site.
• A bioglue at the anastomosis site contains precipitated amorphous thermoplastic biocoacervate + crosslinkers and seals the end retention elements.

Practical enforcement angle: If the biocoacervate formulation is used only in the tube but not in the thread/wrap, claim 1 is vulnerable because it requires the thread/wrap biomaterial to be formed from the same precipitated amorphous thermoplastic biocoacervates.

Doctrine-of-equivalents risk increases with broad solvent/protein/GAG “lists”

Even if an accused product uses different proteins, GAGs, or solvents not enumerated, doctrine-of-equivalents arguments become more credible because the independent claim already requires the concept of soluble primary proteins + glycosaminoglycans + biocompatible solvents. The dependent claims’ extensive lists signal that the patentee viewed many variants as within the invention’s working range.

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How can competitors design around US 10,016,534 without “precipitated amorphous thermoplastic biocoacervates”?

Design-around vector 1: Avoid “thermoplastic” behavior of the coacervate phase

If the biomaterial behaves as a non-thermoplastic gel, a crosslinked thermoset with different physical properties, or a precipitated phase that is not “thermoplastic,” claim 1’s anchor limitation becomes harder to satisfy.

Design-around vector 2: Replace biocoacervate with different carrier chemistry

The claim ties system components to precipitated amorphous thermoplastic biocoacervate(s) including soluble or solubilized primary proteins + GAG + solvent. Using:

• a conventional elastomer coating,
• a different protein-polysaccharide complex not formed as a biocoacervate,
• or a different microphase assembly method, could remove literal infringement.

Design-around vector 3: Change the sealing mechanism at the anastomosis

Claim 1 requires bioglue with precipitated amorphous thermoplastic biocoacervate + crosslinkers that seals the threads/wraps.

Competitors can reduce risk by:

• sealing with a non-biocoacervate adhesive,
• sealing via mechanical coupling only,
• or using a different class of sealant not matching the biocoacervate definition.

Design-around vector 4: Remove pharmacologic delivery to the anastomosis

The threads/sutures/wraps in claim 1 must comprise biomaterial from the biocoacervate and include pharmacologically active agents delivering them to the anastomosis site.

If a competitor uses pharmacologic loading in the tube (or elsewhere) but not in the threads/wraps, claim 1’s deliver-to-anastomosis element can be avoided.

Design-around vector 5: Keep tube/bioglue but alter the thread/wrap biomaterial composition

Because claim 1 requires biocoacervate biomaterial for both tube component and thread/wrap component, using a different biomaterial in the threads/wraps can avoid literal infringement even if the tube and bioglue use biocoacervates.

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What do claim 16 and claim 17 add versus claim 1? (System without explicit delivery biomaterial identity across parts)

Claim 16 is structurally similar to claim 1 but:

• It does not include the explicit “wherein the threads, sutures and/or wraps deliver the one or more pharmacologically active agents…” language inside claim 16.
• It requires:
  • Tube component includes precipitated amorphous thermoplastic biocoacervate tube biomaterial.
  • Threads/wraps at ends comprise components including at least one biocoacervate biomaterial.
  • Bioglue seals threads/wraps at an anastomosis site.
• It omits the explicit “pharmacologically active agents” requirement in claim 16.

Claim 17 then adds:

• Threads/sutures/wraps further comprise pharmacologically active agents and deliver them to the anastomosis site.

Implication: Claims 1 and 17 align on “pharmacologic delivery at anastomosis,” but claim 16 is positioned to capture sealing and biocoacervate structure even when active delivery elements are not asserted. This gives the patentee flexibility in infringement strategy depending on what the accused product loads where.

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How strong is the patent estate for US 10,016,534 based on the claim breadth? (Strength indicators and weak points in the claim language)

Strength indicators

• The invention is drafted as a system claim tying together tube material, thread/wrap material, and bioglue function at the anastomosis. This can prevent “partial” design-arounds if competitors try to split components across different suppliers or formulations.
• The biocoacervate definition is detailed (protein + GAG + solvent + precipitation + amorphous thermoplastic), but the dependent claims’ wide enumerations suggest robust coverage across biomolecule variants.
• Crosslinker lists indicate the patentee anticipated multiple sealing chemistries using biocoacervate frameworks.

Weak points

• Claim interpretation depends on what qualifies as a “precipitated amorphous thermoplastic biocoacervate.” If prior art or prosecution history narrowed this definition, enforceability could narrow with it.
• The claims are broad on drug classes and protein lists but still require the same core biocoacervate chemistry across tube/thread and the bioglue. If a competitor uses different materials in any one of those locations, the system claim can be harder to prove.

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What patents likely overlap with US 10,016,534? (Biocoacervate adhesives + protein-GAG thermoplastic coacervate biomaterials + vessel grafts)

No patent overlap can be enumerated accurately without access to the patent number’s bibliographic data (assignee, priority date, full specification, and cited references). The claim text alone does not provide enough to identify the family, forward citations, or competitor estates.

What can be stated from the claim’s technical features is that the likely overlap zones, globally and in the US, are:

• coacervate/complex coacervation biomaterials using proteins + polysaccharides/GAGs,
• bioadhesives/sealants using crosslinkers for tissue apposition and anastomosis sealing,
• drug-eluting surgical sutures and wrap delivery systems,
• vascular graft coatings using biomimetic protein-GAG layers,
• and scaffolded tubular grafts with polymer-encapsulated biomaterials.

For infringement and invalidity analysis, these zones would be searched as:

• coacervate precipitation methods,
• thermoplastic vs thermoset characterization of coacervates,
• crosslinker-compatible protein-GAG systems,
• and anastomosis-site sealing formulations.

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What generic entry risks exist for products built on the same biocoacervate vessel graft platform? (Device vs. biologic vs. drug mechanics)

US 10,016,534 is drafted as a device/system claim, not as a single small-molecule or biologic composition claim. “Generic entry” in the FDA sense does not map cleanly. Risk for competitors is instead determined by:

• whether they can ship an FDA-cleared or approved device without infringing,
• whether they can obtain clearance via predicate technology not using the same biocoacervate + crosslinker bioglue sealing approach,
• and whether Paragraph IV-style challenges apply (typically not for devices in the same way as for drug patents).

Actionability: If an accused product uses the same precipitated amorphous thermoplastic biocoacervate structure in tube and bioglue sealing, it is exposed to system-level injunction leverage.

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Timeline: When does exclusivity end for US 10,016,534?

No exclusivity timeline can be computed from claim text alone because it requires:

• the patent’s filing date, priority date(s), and whether any terminal disclaimer or adjustments apply. Without those bibliographic facts, any date would be non-actionable.

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Key Takeaways

• Claim 1 is a tightly coupled system claim: it requires a biocoacervate thermoplastic protein-GAG solvent biomaterial in the tube, the same biocoacervate concept in threads/sutures/wraps carrying pharmacologically active agents, and a bioglue at the anastomosis site made from the same biocoacervate plus crosslinkers.
• The broad protein/GAG/solvent and active-agent lists increase coverage across formulations, but the enforceability hinges on whether accused materials meet the specific “precipitated amorphous thermoplastic biocoacervate” definition and whether the biocoacervate chemistry is used in the required system parts.
• Design-around focus: break the system link by changing (a) the thermoplastic coacervate nature, (b) the biocoacervate definition, (c) the sealing chemistry at the anastomosis, or (d) pharmacologic loading location such that it is not delivered by the claimed end threads/wraps.
• Claims 16–17 position fallback coverage for sealing using biocoacervates (claim 16) and then adding active-agent delivery via end threads/wraps (claim 17).

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FAQs

1. Does US 10,016,534 cover vascular grafts without drug-eluting threads/sutures if the bioglue still seals?
   Claim 16 can cover sealing and biocoacervate structure, while pharmacologic delivery is captured in claim 17.

2. Can a competitor use the same protein and GAG ingredients but a non-precipitated or non-thermoplastic coacervate and avoid infringement?
   If “precipitated amorphous thermoplastic biocoacervate” is not met, literal infringement arguments weaken for claim 1.

3. How important is crosslinker identity for the bioglue under the independent claim?
   Crosslinker presence is required by claim 1 conceptually; specific crosslinkers are detailed in dependent claims.

4. Is scaffold-coating architecture mandatory to infringe?
   No. Claim 3 adds scaffold encapsulation as a dependent limitation.

5. What is the most practical test to assess infringement risk for a candidate product?
   Map whether tube component, thread/wrap biomaterial, and anastomosis bioglue all use the same precipitated amorphous thermoplastic protein-GAG-solvent biocoacervate concept.

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References

No sources are cited because US 10,016,534’s patent record, prosecution history, cited prior art, and assignee/family information were not provided in the prompt, and the claim text alone does not support reliable bibliographic citation.

Details for Patent 10,016,534

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bayer Healthcare Pharmaceuticals Inc.	TRASYLOL	aprotinin	Injection	020304	December 29, 1993	10,016,534	2029-11-17