Details for Patent: 9,254,267

Summary for Patent: 9,254,267

Title:	Composite hydrogel drug delivery systems
Abstract:	Compositions and methods are provided to control the release of relatively low molecular weight therapeutic species through hydrogels by first dispersing or dissolving such therapeutic species within relatively hydrophobic rate modifying agents to form a mixture. The mixture is formed into microparticles that are dispersed within bioabsorbable hydrogels, so as to release the water soluble therapeutic agents in a controlled fashion. Methods of using the compositions of the present invention in therapeutic systems are also provided.
Inventor(s):	Amarpreet S. Sawhney
Assignee:	Incept LLC
Application Number:	US12/218,152
Patent Claim Types: see list of patent claims	Use;

Scope and claims dissection of US Patent 9,254,267 and the US gel microdomain hydrogel patent landscape

US 9,254,267 covers methods for making covalently crosslinked, bioabsorbable hydrogel matrices in which hydrophobic domains (non-gaseous) are formed in situ and the therapeutic agent is associated with those domains. The enforceable core is the combination of: (i) covalent crosslinking of hydrophilic synthetic macromers into a continuous hydrogel, (ii) formation of dispersed hydrophobic domains within the forming matrix, and (iii) drug association with the hydrophobic domains, with additional claim scaffolding for release-rate modifiers (fatty acids/triglyceride-type), therapeutic class and physicochemical constraints, and hydrogel architecture details (PEG/macromers, electrophile-nucleophile chemistry, microdroplets/microparticles/micelles, and micrometer domain size).

What does US Patent 9,254,267 claim cover in the US (scope of claims 1 to 25)?

Featured-snippet answer: The patent claims a gel manufacturing method where hydrophilic synthetic macromers are covalently crosslinked into a continuous bioabsorbable hydrogel in the presence of a hydrophobic material and a therapeutic agent, producing dispersed non-gaseous hydrophobic domains that carry the drug (the therapeutic agent is associated with the hydrophobic domains).

Claim 1: The enforceable “center of gravity”

Claim 1 is a method claim with a process-product functional nexus. It requires all of the following limitations:

1. Reacting hydrophilic, synthetic macromers via covalent reactions.
2. Forming a continuous, bioabsorbable, synthetic, covalently crosslinked hydrogel matrix.
3. Doing so in the presence of a hydrophobic material and a therapeutic agent.
4. Creating a plurality of non-gaseous hydrophobic domains from the hydrophobic material.
5. Dispersing those hydrophobic domains in the continuous hydrogel matrix.
6. The therapeutic agent is associated with the hydrophobic domains.

Business implication: design-arounds must attack at least one mandatory element. The easiest “surface” to change is usually the hydrophobic domain architecture (e.g., avoid formation of hydrophobic domains from the hydrophobic material during crosslinking), or ensure the therapeutic agent is not associated with those domains (e.g., molecularly dispersed in the hydrophilic network), or avoid covalent crosslinking by switching to physically crosslinked or ionic systems. Changing drug class alone does not avoid claim 1 if association and hydrophobic-domain formation remain.

Claim 2 to 4: Release rate modifying agent carve-out

• Claim 2: hydrophobic material comprises a release rate modifying agent.
• Claim 3: release-rate modifier is selected from a defined set of fatty acids and related esters (capric acid and long-chain saturated fatty acids plus multiple methyl/ethyl/benzyl/butyl/isopropyl/hexadecyl style esters; also lauric, undecanoic, behenic, tricosanoic, myristic, palmitic, stearic derivatives).
• Claim 4: broader: release-rate modifier selected from fatty acids and triglycerides.

Business implication: the presence of long-chain fatty acids and triglyceride-type release modifiers is a high-risk formulation element. Even if domain size, microstructure, and PEG chemistry are replicated, using a different release-rate strategy (e.g., degradable crosslinkers, porogens, diffusion barriers not derived from hydrophobic domain-forming agents) can reduce literal overlap with dependent claims 2–4, though claim 1 may still capture the general architecture if hydrophobic domains are still formed and drug association remains.

Claim 5 to 8: Drug property constraints

• Claim 5: therapeutic agent molecular weight < 100,000.
• Claim 6: therapeutic agent molecular weight < 20,000 (narrower).
• Claim 7: water solubility > 0.01 mg/mL.
• Claim 8: therapeutic agent is hydrophobic.

Notable internal tension: Claim 7 (water solubility > 0.01 mg/mL) can coexist with “hydrophobic” if “hydrophobic” is interpreted broadly within the specification context, but in enforcement it creates room for argument over definitions. Practically, these are still dependent claim features and do not narrow the independent claim 1 beyond the general “therapeutic agent” requirement.

Claims 9 to 11: Therapeutic category fallback positions

These are alternative listings:

• Claim 9: growth factor, cytokine, antimitotic, radiation source, antineoplastic.
• Claim 10: antiallergenic, cardiovascular agents, respiratory agents, hormones, metabolism agents, antimicrobial.
• Claim 11: chemotherapeutic, local anesthetics, antihistaminic, antiphlogistics, astringents, vitamins, antifungals, peripheral nervous anesthetics, vasodilators, anti-inflammatory, immunosuppressants.

Business implication: these dependent listings help ensure the claim family covers a broad therapeutic use spectrum. They are not strong design-around levers unless prosecution history or claim construction tightly narrows “member of the group” to a specific biological category.

Claims 12 to 19: Hydrophobic domain morphology and drug hosting

• Claim 12: hydrophobic domains comprise microdroplets.
• Claim 13: comprise microparticles.
• Claim 14: comprise a compound with melting point < 65°C.
• Claim 15: hydrophobic domains comprise surfactants.
• Claim 16: hydrophobic domains formed in situ as hydrogel forms.
• Claim 17: domains comprise micelles (a specific in situ colloidal state).
• Claim 18: hydrophobic domains comprise the therapeutic agents (strongest drug-hosting reading).
• Claim 19: hydrophobic domains size ~1 to 10 microns.

Business implication: this set materially expands scope across multiple dispersed hydrophobic microstructures that are common in controlled release. If a competitor’s system forms oil-in-water droplets, surfactant micelles, or lipid microparticles during gelation and co-localizes the drug to them, it remains a literal risk zone. If the drug is instead covalently conjugated to the hydrogel network, or encapsulated in a separate carrier particle population not formed from the “hydrophobic material” during crosslinking, the “associated with hydrophobic domains” element becomes litigable.

Claims 20 to 25: Process and polymer chemistry extensions

• Claim 20: further comprising forming hydrogel matrix in situ (local gelation in the target site).
• Claim 21: macromers comprise poly(ethylene glycol).
• Claim 22: macromers further comprise a biodegradable portion.
• Claim 23: macromers have free functional groups that are free after crosslinking (suggests residual functionalities post-gelation).
• Claim 24: crosslinking chemistry defined broadly: macromers each comprise at least two electrophilic or at least two nucleophilic groups, then react electrophiles with nucleophiles to covalently form matrix.
• Claim 25: includes a binding ligand disposed within the hydrogel matrix.

Business implication: Claim 24 is a wide crosslinking-chemistry fallback; it is not limited to a particular functional pair and therefore can be hard to design around if the competitor uses common covalent pairings (e.g., Michael-type, Schiff-base followed by reduction (if covalent), amine-reactive electrophiles, thiol-nucleophile systems, etc., depending on how “covalent reaction” is defined in the specification).

How broad is the claim coverage: method “making” vs product features?

Featured-snippet answer: The claims are method claims, but they define product-like structural outcomes (a hydrogel matrix with dispersed hydrophobic domains sized 1–10 microns, in situ formed, drug associated with those domains). That makes infringement analysis functionally dependent on the resulting gel microstructure.

Key breadth drivers:

• “hydrophilic, synthetic macromers” plus “bioabsorbable” plus “covalently crosslinked” defines a class, not a single chemistry.
• “hydrophobic material” is not limited to one chemical family in claim 1. Dependent claims 2–4 narrow to fatty acids/triglycerides/defined ester list.
• “non-gaseous hydrophobic domains” plus “formed in situ” and morphological options (droplets, microparticles, micelles) provides multiple literal pathways.
• “therapeutic agent associated with the hydrophobic domains” is functional and can capture adsorption, partitioning, entrapment, and co-dispersion, depending on claim construction.

Practical risk framing: A competitor using a PEG-based covalently crosslinked gel with biodegradable segments that forms lipid droplets during gelation, and where the drug partitions into those lipid domains, sits squarely within claim 1 even if domain chemistry differs from the enumerated fatty acids in dependent claims.

What patent landscape surrounds US 9,254,267: likely related continuations, family breadth, and adjacent IP themes?

Featured-snippet answer: Patent estates for in situ-forming covalent hydrogels with dispersed hydrophobic microdomains typically include (i) macromer chemistries and crosslinking systems, (ii) lipid/fatty-acid or amphiphile domain formation and size control, (iii) drug loading and association strategies, and (iv) in situ administration and binding ligand incorporation. US 9,254,267 is positioned at the overlap of those themes.

Because you provided only the claim text and not prosecution data, publication numbers, assignee, or citation set, the landscape below is framed to the claim-structure boundaries (what other patents must exist to cover the same “technical space” in US filings). It enumerates the types of adjacent patents that usually coexist in the same family or from different groups, and the specific claim elements that will be searched.

Adjacent US patent clusters to search (by claim-element mapping)

1. Covalently crosslinked synthetic hydrogels using PEG (claim 21 + claim 24 + claim 22)

   • Look for US patents claiming: PEG macromers with electrophilic/nucleophilic groups that covalently crosslink into bioabsorbable matrices.
   • Key terms: “PEG”, “electrophilic”, “nucleophilic”, “covalently crosslinked”, “bioabsorbable”, “in situ gelation”, “hydrogel matrix”.

2. In situ formation of hydrophobic domains during gelation

   • Look for patents claiming: hydrophobic domains/micelles/microdroplets formed as the hydrogel forms, often via emulsification without preformed nanoparticles.
   • Key terms: “in situ formed”, “micelles”, “microdroplets”, “hydrophobic domains”, “dispersed”.

3. Drug partitioning/association with hydrophobic microdomains

   • Look for patents that explicitly require the drug to be associated with lipid/micelle domains within the gel.
   • Key terms: “associated with”, “partitioned into”, “encapsulated in domains”, “hosted by hydrophobic domains”.

4. Release rate modifying agents: fatty acids, triglycerides, long-chain esters (claim 2–4 + claim 14)

   • Look for patents enumerating long-chain fatty acids and esterified fatty acids with melting points and controlled release.
   • Key terms: “capric acid”, “undecanoic”, “behenic acid”, “triglyceride”, “fatty acid esters”, “melting point”.

5. Domain size control

   • Look for claims that tie domain size to release and require a size range (claim 19).
   • Key terms: “1 to 10 microns”, “micron size”, “particle size distribution”.

6. Binding ligand incorporation (claim 25)

   • Look for hydrogel claims containing targeting or binding ligands to retain proteins or growth factors.

How this landscape affects freedom-to-operate (FTO) and design-around

• If a product uses physical crosslinking (thermoreversible or ionic crosslinks) without covalent crosslinking, it weakens claim 1 literal coverage.
• If the system uses preformed drug-loaded microcarriers added to a gel (rather than forming hydrophobic domains from hydrophobic material during polymer network formation), it can avoid “non-gaseous hydrophobic domains being formed from the hydrophobic material”.
• If the drug is not associated with hydrophobic domains (for example, covalently linked to the network or dissolved within the continuous hydrophilic phase), it can avoid the key functional requirement.

What are the likely infringement and claim-construction fault lines?

Featured-snippet answer: The two highest-friction elements are (i) whether the hydrophobic domains are “formed from the hydrophobic material” during covalent gel formation (including whether domains are formed “in situ”), and (ii) whether the therapeutic agent is “associated with” those hydrophobic domains.

Fault line 1: “formed from the hydrophobic material”

In practice, disputes often hinge on whether domains are:

• created during mixing/gelation (true “in situ” formation), versus
• pre-existing entities (pre-made micelles/liposomes/particles) simply embedded into a gel.

Claim 16 and claim 17 heighten the risk if an accused process forms micelles during gelation.

Fault line 2: “therapeutic agent being associated with the hydrophobic domains”

“Associated with” can cover:

• partitioning into hydrophobic domains,
• encapsulation,
• adsorption at interfaces,
• co-localization.

To reduce this risk, a design should ensure drug predominantly partitions into the hydrophilic matrix phase or is covalently tethered.

Fault line 3: domain “non-gaseous” and size (claim 19)

If the domain size falls outside 1–10 microns, dependent claim 19 is not met. But claim 1 does not require a size range. Domain morphology and dispersion state still matter to whether a court views the system as comprising “plurality of non-gaseous hydrophobic domains.”

How to benchmark claim scope vs common competitive hydrogel drug delivery designs?

Featured-snippet answer: Systems that are PEG-based, covalently crosslinked, and load drugs into lipid droplets/micelles formed during gelation are the closest matches to this patent.

Closest matching architectures (highest infringement risk)

• Covalently crosslinked PEG hydrogel (bioabsorbable), formed in situ.
• Long-chain fatty acid or triglyceride release modifiers added during gelation.
• Hydrophobic domains (microdroplets/microparticles) form in the continuous matrix and the drug partitions into them.
• Domain size around microns (or at least discrete hydrophobic domains exist).
• Drug loading relies on hydrophobic association rather than covalent conjugation.

Lower matching architectures (design-around opportunities)

• Physical hydrogels (non-covalent crosslinks) or purely covalent but no hydrophobic-domain formation.
• Drug covalently tethered to hydrophilic network or captured in hydrophilic segments.
• Drug loaded into preformed nanoparticles added after domain formation.
• Hydrophobic additives do not form discrete hydrophobic domains (instead act as homogeneous modifiers).

Key takeaways

• US 9,254,267 is anchored on a method where covalently crosslinked synthetic bioabsorbable hydrogels are formed from hydrophilic synthetic macromers in the presence of hydrophobic material and a therapeutic agent, yielding dispersed non-gaseous hydrophobic domains that host/associate the therapeutic agent.
• Dependent claims expand scope across: fatty acid/triglyceride release modifiers, PEG and biodegradable macromers, broad electrophile-nucleophile covalent crosslinking, microdroplets/microparticles/micelles, in situ domain formation, and domain size ~1–10 microns.
• Design-around is most feasible by breaking at least one of the claim 1 essentials: remove covalent crosslinking, prevent hydrophobic domain formation from the hydrophobic material during gelation, or prevent the therapeutic agent from associating with those hydrophobic domains.

FAQs

1. What specific process elements most often determine infringement for hydrophobic domain hydrogel claims?
   Whether hydrophobic domains form during gelation “from” the hydrophobic material and whether the drug partitions into or is co-localized with those domains.

2. Do dependent claims on fatty acids/triglycerides control infringement if claim 1 is met anyway?
   No. Dependent claims narrow scope, but claim 1 can still be infringed even without fatty acids/triglycerides if the core architecture and drug association are present.

3. How can a competitor avoid the “in situ formed hydrophobic domains” limitation?
   Use preformed hydrophobic carriers introduced after covalent gel crosslinking, avoiding domain creation during polymer network formation.

4. Does domain size matter if claim 19 is not satisfied?
   Size helps only for claim 19; claim 1 does not require a size range, so discrete hydrophobic domains can still satisfy claim 1.

5. What polymer chemistry changes most likely avoid claim 24?
   Avoid the stated electrophilic/nucleophilic covalent reaction framework (and, more generally, avoid covalent crosslinking as required by claim 1).

References (APA)

1. Claims text provided in the prompt for United States Drug Patent 9,254,267.

Drugs Protected by US Patent 9,254,267

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 9,254,267

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	5486399
Canada	2339482
European Patent Office	1104286
Japan	2003523926