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United States Patent 10,064,948: What the Claims Cover and Where the Landscape Leaves Exposure

United States Patent 10,064,948 protects a macromolecule-loaded, bioresorbable crosslinked polymer made by polymerizing (1) a defined ester-/amide-forming monomer class (formula I), (2) a linear bioresorbable block-copolymer crosslinker (formula II or variants), and (3) a thiol chain transfer agent, with the loaded payload restricted to proteins and nucleic acids. Dependent claims expand coverage into specific crosslinker block sequences, specific monomers, optional exo-methylene cyclic monomers, and defined injectable particle/implant forms.

The patent’s enforceable core is narrow in chemistry but broad in application language. The landscape risk is that large portions of the claimed combination sit on a continuum of known design choices in drug-delivery hydrogels/particles: (meth)acrylate-type thiol-mediated radical polymerization, PLA/PEG/PCL/PLGA block-crosslinker concepts, micro-/meso-particle formulations for controlled resorption, and protein or nucleic acid encapsulation.

1) What the independent claim actually requires (claim 1 as the core)

Claim 1 structure (minimum element set)

Claim 1 requires all of the following in one polymer system:

(i) Polymerizable monomer(s) of formula (I)
General form: (CH₂=CR₁)CO–K

K is O–Z or NH–Z
Z is one of:
- (CR₂R₃)ₘ–CH₃
- (CH₂–CH₂–O)ₘ–H
- (CH₂–CH₂–O)ₘ–CH₃
- (CH₂)ₘ–NR₄R₅
m: 1 to 30
R₁–R₅: independently H or C1–C6 alkyl

This reads as a (meth)acrylate-type family where the ester/amide oxygen or nitrogen is attached to a substituted chain/oligo segment of defined structure.

(ii) A bioresorbable block copolymer crosslinker (formula II)
Claim 1 requires the crosslinker to be:

linear
selected from PEG, PLA, PGA, PLGA, PCL
and defined by formula (II):
(CH₂=CR₇)CO–(Xₙ)ⱼ–PEGₚ–Y_k–CO–(CR₈=CH₂)

Key features:

Terminal groups: (CH₂= C R₇)CO– and –CO–(C R₈ = CH₂) (polymerizable end groups)
X and Y: each independently PLA, PGA, PLGA, or PCL
n, p, k: 1–150 for n and k; p 1–100
j: 0 or 1

(iii) At least one chain transfer agent = thiol

cycloaliphatic or aliphatic thiol
2 to 24 carbon atoms

(iv) Payload restriction

loaded macromolecule is proteins or nucleic acids.

Claim 1 practical translation

Enforcement attaches to polymers that match:

a specific monomer family (formula I),
crosslinker topology of linear block copolymer with polymerizable acrylate/methacrylate-like ends (formula II),
thiol chain transfer (2–24 carbons),
and encapsulated payload category.

This is not a generic “biodegradable crosslinked polymer” claim. It is a composition-by-structure claim with mechanistic polymerization features indirectly enforced through the required ingredients.

2) Claim scope expansion: what dependent claims add (and what they risk)

Claim 2: specific formula patterns for block sequences

Claim 2 enumerates crosslinker compositions that are variants of the formula (II) pattern, including:

CO–PLAₙ–PEGₚ–PLA_k–CO
CO–PGAₙ–PEGₚ–PGA_k–CO
CO–PLGAₙ–PEGₚ–PLGA_k–CO
and mixed PEG-end blocks such as CO–PLAₙ–PEGₚ–PCL_k–CO (as reflected by the listed combinations).

Impact: creates additional fallback positions. The enumerated list reduces breadth while improving clarity for validity arguments.

Claim 3: enumerated monomer examples

Claim 3 specifies monomer selection from a list including:

sec-butyl acrylate / n-butyl acrylate / t-butyl acrylate
t-butyl methacrylate
methyl methacrylate
dialkylaminoethyl or aminopropyl (meth)acrylates (e.g., N-dimethylaminoethyl(methyl)acrylate, N,N-dimethylaminopropyl-(meth)acrylate, etc.)
poly(ethylene oxide)-terminated acrylates/methacrylates, including methoxy/butoxy PEG methacrylates and “poly(ethylene glycol) methyl ether methacrylate”

Impact: narrows claim 1 to named monomers that sit in common “reactive diluent” and “PEG-methacrylate” territory. That increases prior-art pressure if those monomers were already used in thiol-mediated biodegradable networks.

Claim 4–6: alternative formulation with optional exo-methylene cyclic monomers

Claim 4 introduces:

a crosslinker defined by having (CH₂=CR₆)– groups at both extremities (not necessarily the full formula II block pattern as in claim 1),
and adds (iv) further at least one cyclic monomer with an exo-methylene group (formula III),
plus it keeps the thiol chain transfer agent.

Claim 5 narrows cyclic monomer to:

2-methylene-1,3-dioxolane
2-methylene-1,3-dioxane
2-methylene-4-phenyl-1,3-dioxolane
2-methylene-1,3-dioxepane
5,6-benzo-2-methylene-1,3-dioxepane
2-methylene-1,3,6-trioxocane

Claim 6 broadens claim 4 with an additional optional component:

a further monomer of formula (V): (CH₂=CR₁₁)CO–M–F, where F is a charged/ionizable/hydrophilic/hydrophobic group (≤100 atoms) and M is a single bond or linker (1–20 carbons).

Claim 6 also keeps the cyclic monomer optional.

Claim 7 lists examples of F groups, including:

COOH/COO⁻
SO₃H/SO₃⁻
PO₄H₂ / PO₄H⁻ / PO₄²⁻
NR₉R₁₀, NR₉R₁₂R₁₀⁺
aryl/heteroaryl and bulky solubilizing motifs
crown ether, cyclodextrin

Impact: these claims attempt to capture a wider class of networks with:

ring-opening/propagating exo-methylene monomers,
ionizable monomers to tune nucleic acid loading/retention,
while retaining the thiol and payload categories.

The trade-off is that exo-methylene cyclic monomers and charge-functional acrylates are historically common in drug-delivery polymer chemistry, raising obviousness risk unless the specific combination with the defined biodegradable linear block crosslinker and thiol chain transfer is shown to be non-obvious.

Claim 8: payload expansion to biologics and gene vectors

Claim 8 lists:

enzymes, antibodies, cytokines, growth factor, coagulation factors, hormones
plasmids, antisense oligonucleotides, siRNA, ribozymes, DNAzymes, aptamers
cationic polymers for nucleic acid loading
bone morphogenetic proteins, angiogenic factors, VEGF, TGF-beta
inhibitors of angiogenesis

Claim 9–12 and 14–18: product forms and resorption/particle specs

Claim 9 covers the physical forms:

film, foam, particle, lump, thread, sponge.

Claim 11 introduces an injectable composition with two populations of spherical particles:

polymer (a): 50–500 μm diameter; 2 days to 3 weeks resorption
polymer (b): 50–500 μm diameter; 1 to 3 months resorption
both are based on the polymers of claim 1

Claim 12 requires particle diameter differences between (a) and (b).

Claim 18 adds:

(a) 100–300 μm
(b) 300–500 μm

Claim 13 covers an implant containing the polymer. Claim 14 covers implantation into tissue types and anatomical sites:

tissues, brain/spinal cord, bone defects, internal anatomical spaces, body cavities, ducts, vessels.

Claim 10 defines a pharmaceutical composition with a pharmaceutically acceptable carrier.

Impact: these claims are strong on formulation scope but may be vulnerable if resorbable particle systems with those size and resorption windows were already conventional for similar payload categories.

3) Critical read of novelty: where claim breadth likely meets prior art

A) Polymerization mechanics are not the differentiator

Claim 1 requires:

radical polymerizable groups on the monomer and the crosslinker,
plus a thiol chain transfer agent.

Thiol-mediated radical polymerization with acrylate or methacrylate monomers is a mature area. Many delivery polymers use thiols as chain transfer agents to control molecular weight and network properties. That reduces novelty if the only difference is that the crosslinker is a particular PEG/PLA/PGA/PLGA/PCL block architecture.

B) The crosslinker architecture looks “known building blocks assembled”

Formula (II) is essentially:

PEG block in the middle
PLA/PGA/PLGA/PCL block on both sides (order depends on X and Y choices)
with polymerizable ends.

This resembles a common “PEG-centered biodegradable block copolymer with functional ends” strategy. Prior art exposure is high if comparable end-functional biodegradable block copolymers were used to crosslink PEG/PLA-based matrices for protein/nucleic acid delivery.

C) Monomer family in claim 1 overlaps with standard degradable/acrylate chemistry

Formula (I) includes a large portion of:

alkyl (meth)acrylates (e.g., butyl acrylate derivatives)
amine-functional (meth)acrylates (for nucleic acid complexation)
PEG-terminated methacrylate/acrylate macromonomers (for hydrophilicity and retention)

Claim 3 enumerates several monomers that are frequent in delivery polymer work. This makes invalidity arguments easier: the claim may be “a list of standard monomers tied to a standard process and a particular crosslinker.”

D) Payload restriction to proteins and nucleic acids is broad, not limiting

Claim 1’s payload limitation is category-level:

proteins and nucleic acids are widely used in biodegradable carrier systems. Dependent claims then add extensive examples but do not require specific payload sizes, sequences, or binding chemistry.

This can cut against inventive step if prior art already disclosed encapsulating proteins and nucleic acids using similar biodegradable crosslinked matrices.

E) Optional cyclic exo-methylene monomers and charged monomers are also likely known knobs

Claim 4–7 incorporate:

exo-methylene cyclic monomers (dioxolane/dioxane/dioxepane/trioxocane classes)
and optional charge/ionizable monomers (formula V)

These are typical tools to:

tune hydrophilicity, degradation, and polymerization characteristics,
tune nucleic acid complexation and release.

The risk is that a skilled person could combine them with known degradable PEG/PLA/PGA block crosslinkers without inventive insight, unless the claim ties the components in a specific non-obvious way.

4) Patent landscape logic: likely claim competition and design-around vectors

A) Where competitors can carve around

Based on the structure of claim 1 and dependent claims, the most direct design-around routes are:

Remove the thiol chain transfer agent requirement
If a rival uses photopolymerization, enzyme-initiated polymerization, or non-thiol chain transfer strategies, it can avoid the “thiol chain transfer agent 2–24 carbon atoms” element.
Use a different crosslinker topology
Claim 1 requires a linear bioresorbable block copolymer crosslinker with polymerizable ends and the explicit PEG plus X/Y block structure per formula (II). Rivals using:
- non-linear crosslinkers,
- star-shaped PEG architectures,
- block copolymers without the exact formula (II) arrangement, may evade infringement.
Use different monomer families than formula (I)
Even within (meth)acrylates, substituent structure drives claim compliance. A rival can shift to alternative vinyl monomers or different ester/amide structures not falling inside (I).
Avoid the payload category restriction in manufacture
If a competitor’s payload is neither “proteins” nor “nucleic acids” per claim language, it can potentially avoid the claim, though most delivery competitors often use those payloads.
Alter particle engineering specs Claims 11–12 and 18 specify resorption windows and particle diameter ranges. A rival with different particle size distributions or different resorption profiles can reduce the chance of matching formulation-specific claims (though claim 1 and broad composition claims still matter).

B) Where infringement risk concentrates

Infringement risk is highest where a product matches:

thiol-mediated acrylate polymer networks,
using linear PEG-centered PLA/PGA/PLGA/PCL block crosslinkers with polymerizable end groups,
loading proteins or nucleic acids,
and using particle size/resorption targets if invoking claims 11–12 and 18.

5) Claim-by-claim enforcement map (what each claim likely captures)

Claim	Enforces	Key differentiator elements
1	Core polymer	Formula (I) monomer + formula (II) linear PEG-centered biodegradable block crosslinker + thiol chain transfer (2–24 C) + payload is proteins or nucleic acids
2	Crosslinker subset	Enumerated PEG-PLA/PGA/PLGA/PCL block sequence combinations
3	Monomer subset	Enumerated alkyl acrylates/methacrylates, amino(meth)acrylates, and PEG-terminated (meth)acrylates
4	Alternative network variant	Crosslinker has polymerizable end groups at both extremities + thiol CTA + cyclic exo-methylene monomer (formula III) + payload proteins/nucleic acids
5	Cyclic monomer subset	Specific methylene dioxolane/dioxane/dioxepane/trioxocane exo-methylene monomers
6	Network variant with charged monomer	Adds optional charge/ionizable/hydrophilic/hydrophobic monomer (formula V) alongside thiol CTA and optional exo-methylene cyclic monomer
7	Charge group subset	Enumerated F groups including acids/sulfonates/phosphates/amines and macrocyclic carriers (crown ether, cyclodextrin)
8	Payload examples (broader list)	Proteins including cytokines, growth factors, angiogenesis factors; nucleic acids including siRNA, antisense, plasmids, aptamers
9	Physical form	Film/foam/particle/lump/thread/sponge
10	Formulation with carrier	Polymer in association with pharmaceutically acceptable carrier
11	Injectable dual-particle resorption scheme	Spherical particles 50–500 μm; two resorption windows (2 days to 3 weeks; 1–3 months)
12	Diameter difference between particle populations	(a) and (b) different diameters
13	Implant	Implant containing the polymer
14	Implant sites	Tissue, brain/spinal cord, bone defects, cavities, ducts/vessels
15	Chain transfer agent with extra functionality	Thiol CTA plus optional amino/hydroxy/carboxy functional group
16	Cyclic monomer subset (variant)	Specific cyclic monomers within formula (III) group
17	Payload subset	Growth hormones, antibodies (e.g., infliximab, bevacizumab), gene-delivery-related polypeptides, etc.
18	Specific particle diameter bands	(a) 100–300 μm; (b) 300–500 μm

6) Critical assessment: where the claim set is strong vs exposed

Strengths

Ingredient-level specificity: formula-based monomer and crosslinker structures reduce the chance that generic prior art anticipates the full claim.
Topology control: “linear” crosslinker and PEG-centered block pattern narrows composition.
Mechanistic ingredient requirement: thiol chain transfer agent is a concrete input that is less common to omit in delivery polymerizations.

Exposures

Large overlap with conventional delivery polymer chemistry: acrylate/methacrylate monomers including alkyl acrylates, PEG methacrylates, and amino(meth)acrylates are common.
Crosslinker concept appears modular: PEG-centered biodegradable block crosslinkers with polymerizable ends can be found across delivery literature and patents; claim novelty must ride on the specific formula boundaries.
Payload restriction is not limiting enough: proteins and nucleic acids are broadly disclosed across the field.
Dependent “add-ons” likely increase prior-art reach: exo-methylene cyclic monomers and charge-functional vinyl monomers are standard tuning knobs, which can make inventive-step arguments more difficult.

Key Takeaways

Claim 1 is the enforcement backbone: it requires a precise combination of (i) formula (I) (meth)acrylate-type monomers, (ii) a linear PEG-centered biodegradable block copolymer crosslinker (formula II), (iii) a thiol chain transfer agent (2–24 carbons), and (iv) protein/nucleic acid payloads.
Dependent claims broaden the architecture without changing the core ingredient triad; they mainly add crosslinker variants, monomer examples, optional exo-methylene cyclic monomers, and optional charge-functional monomers.
Formulation claims (11–12 and 18) are narrower because they require specific particle size and resorption windows for an injectable dual-population scheme.
Landscape risk concentrates on obviousness: many claim elements correspond to mature, combinable building blocks in delivery polymer chemistry. The patent’s differentiation must hinge on the exact structural constraints of formulas (I), (II) and the specified thiol chain transfer role.

FAQs

1) What is the single biggest element that competitors must match to infringe claim 1?

The polymer must include all three: a formula (I) monomer, a formula (II) linear PEG-centered biodegradable block copolymer crosslinker, and a cycloaliphatic/aliphatic thiol chain transfer agent (2–24 carbons), with protein/nucleic acid loading.

2) Do claims protect only injectable products?

No. Claims cover polymers in multiple physical forms (claim 9), pharmaceutical compositions (claim 10), and implants (claims 13–14), with injectable-specific particle/resorption limitations only in claims 11–12 and 18.

3) Which dependent claim most increases freedom to tune nucleic acid loading?

Claim 6–7 because they add optional charged/ionizable/hydrophilic/hydrophobic monomer (formula V) with enumerated F groups.

4) How can an alternative polymerization strategy reduce infringement risk?

By avoiding the required thiol chain transfer agent element (claim 1 and claim 4–6), or by not using a thiol meeting the specified cycloaliphatic/aliphatic 2–24 carbon definition.

5) Are the particle size and resorption windows enforceable only for a dual-particle injectable product?

Yes. The explicit diameter (50–500 μm) and resorption window split between particle populations (2 days to 3 weeks vs 1–3 months) is in claim 11, with additional diameter bands in claim 18.

References

[1] United States Patent No. 10,064,948. Claims provided in the user prompt (claims 1–18).

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	August 24, 1998	10,064,948	2032-03-09
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	February 26, 2004	10,064,948	2032-03-09
Kiniksa Pharmaceuticals (uk), Ltd.	ARCALYST	rilonacept	For Injection	125249	February 27, 2008	10,064,948	2032-03-09
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 10,064,948

Summary for Patent: 10,064,948