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Patent landscape, scope, and claims: |
United States Patent 10,689,346: Scope, Claims, and Patent-Landscape Impact for Plasma Kallikrein-Targeting Therapy
What is the claim scope of US 10,689,346 (method of treatment with Formula II compounds)?
US 10,689,346 is a US utility patent in the pharmacology space focused on inhibiting or mitigating “unwanted plasma kallikrein activity” through administration of a compound of Formula (II) (and pharmaceutically acceptable salts). The asserted claim structure is a classic “Markush-style” breadth stack: broad chemical genus + broad route-free therapeutic method + multiple claim-dependent carve-outs around substituent classes, heterocycles, salts, enantiomers, and disease embodiments.
Independent claim structure (Claim 1)
Claim 1 recites a method of treating a disease/condition characterized by unwanted plasma kallikrein activity, comprising administering:
- A therapeutically effective amount of a compound of Formula II, or a pharmaceutically acceptable salt of that compound.
- The claim then expands into an extensive definition of:
- X (core substituent options),
- Y-R4 (linker plus variable R4 group),
- Z (substituent set or aromatic heterocycle set),
- R1c, R2, R3, R3a, R4 (additional substitution variables),
- and includes multiple “optionally substituted” regimes plus stereochemical rules.
The key enforcement axis is that Claim 1 covers any Formula II compound that falls inside the defined combinatorial chemical language, when administered for the targeted kallikrein-associated diseases/conditions.
Claim-dependent narrowing (Claims 2-26)
The dependent claims reduce scope by fixing:
- X choices (Claims 2-3),
- the specific fragment for “X-Y” (Claim 4),
- disease/chemical substituent specifics like:
- R3 aryl pattern (Claims 5, 8-10),
- Z substitution limits (Claims 11-12),
- R1c substitution options (Claims 13-15),
- R2 substitution options (Claim 16),
- specific compound selections and embodiments (Claims 17-18), plus:
- enantiomeric form (+) and (-) (Claims 19-20),
- salt forms including hydrochloride and bis(hydrochloride) variants (Claims 21-26).
From a freedom-to-operate perspective, the dependent claims create multiple “ladder steps” of coverage. Even if a competitor designs around the broad genus, they may still land inside narrower dependent embodiments if they use the same:
- absolute configuration (Claims 19-20),
- salt form (Claims 21-26),
- and specific substituent assignments (Claims 5, 8-16; 11-15).
Disease/condition scope breadth (Claims 27-38)
Claim 27 defines an expanded disease list tied to unwanted plasma kallikrein activity. Claim 28-29 and Claim 31-32 carve out:
- angioedema and hereditary angioedema as specific diseases.
Claims 30, 33-36 repeat broad selection sets for additional dependents (notably referencing specific claim roots tied to enantiomer/salt selections).
Claims 36-38 further specify angioedema/hereditary angioedema under particular compound/salt dependencies.
Net effect: the patent frames the same chemical genus as usable across a wide range of inflammatory/vascular injury and thromboinflammatory contexts, even though the strongest market pull is typically angioedema and hereditary angioedema.
What do the claims cover chemically (Formula II variable language that drives infringement risk)?
The chemical scope is dominated by a Markush genus around Formula II with a multi-parameter substitution system.
Core “X” options (Claim 1’s X definition)
X includes both:
- “carbonyl-derived” and “amine-containing” patterns (e.g.,
—C(NH2), —C(NRaRb), —C(NO2))
- heteroatom-rich sulfonamide and sulfoxide/sulfone classes (e.g.,
—C[S(O)nRa], —C[—S(O)2Rc], —C[S(O)(ORc)])
- aryl and halogen branches (e.g.,
—C(halogen), —C[aryl(C1-C5)alkyl])
- and an “N” alternative.
Claim 2 and Claim 3 then narrow to subsets:
- Claim 2 allows X to be a smaller set (CH, C(OH), C(O(C1-C6)alkyl), —C(NH2), —C(NRaRb), —C(halogen), alkenyl variants, N).
- Claim 3 limits X to CH.
“Y-R4” substituent system
Claim 1 defines Y-R4 as one of many structural motifs, including:
- alkylated and amino-linked moieties (e.g.,
—((C1-C6)alkyl)-R4, —CH2NH-R4, —CH2N((C1-C6)alkyl)-R4)
- cyclic/amino/heterocycle attachments (e.g.,
—N[(C3-C8)cycloalkyl(C1-C6)alkyl]R4, -heterocyclyl-R4)
- oxy and thioethers (
—OR4, —OCH2—R4, —SCH2R4, —SR4)
- and carbonyl-containing options (e.g.,
—CH2C(O)—R4, —NHC(O)—R4).
Claim 4 narrows “X-Y” to specific fragments:
—CHNHCH2——C(OH)CH2CH2——CHOCH2—
Z variable: substituents or heteroaromatic replacement
Claim 1 allows Z to be:
- absent, or
- one or more substituents selected from a large list (halo, hydroxy, alkyl, CF3/OCF3, alkoxy/aryloxy, amino/aminoalkyl, cyano, carbamoyl-like
—C(O)NH2 options, sulfonyl groups, nitro, cyclic groups, and multiple substituted carbonyl/sulfonyl amine patterns),
- or a 5- or 6-membered aromatic heterocycle containing 1 to 4 heteroatoms from N/O/S.
Claim 11-12 narrow Z in dependent claims to fluoro/chloro or specific fluorinated/chlorinated patterns and a specific cycloalkyl substitution.
R1c, R2, R3, R3a, R4
These variables provide further breadth:
-
R1c is selected from a set including halo, aminoalkyl, alkoxy, cyano, hydrazide-like features (—C(═NH)NH2, —CONRaRb), and sulfonyl (—SO2CH3).
- Dependent claims fix R1c to aminomethyl (Claim 13), cyano (Claim 14), or —SO2CH3 (Claim 15).
-
R2 is broad: halo/alkyl/cycloalkyl/fluoroalkyl/OMe/silane —Si(CH3)3/amide/carbocy acid-like —C(O)OH/cyano/phenyl.
- Dependent Claim 16 fixes R2 to: CH3, CF3, tert-butyl, cyclopropyl, OCH3, Si(CH3)3, CONH2, cyano, phenyl.
-
R3 is an aryl/heteroaryl/carbocyclyl/heterocyclyl or phenyl-based structure.
- Claim 5 narrows R3 to phenylene-R3a.
- Claims 8-10 fix R3 to phenyl and R3a to OH, NH2, CN with positional patterns.
-
R3a is either absent or is substituted from a broad substituent family or an aromatic heterocycle set.
- This adds another Markush layer.
-
R4 is itself broad (H, hydroxy, alkyl/cycloalkyl/heterocyclylalkyl/aryl/heteroaryl/CH2OH, amino, cyano, etc.).
- Claim 7 fixes R4 to cyclopropyl.
Stereochemical scope
Claim 1 includes: “The stereochemical configuration at any chiral center is R, S, or a mixture of R and S.” Dependent claims then carve out:
- (+) enantiomer (Claim 19),
- (−) enantiomer (Claim 20).
This means the base genus covers racemates and mixtures, and the dependents separately lock in absolute configuration coverage.
Salt scope
The dependent claims cover:
- hydrochloride salt (Claims 21, 23, 25),
- bis(hydrochloride) salt (Claims 22, 24, 26).
If a competitor uses a different counterion, they can sometimes design around the salt-dependent claims, but they still face risk under the base method claim if the compound free base falls within Formula II.
What conditions are covered (therapeutic indications as infringement hooks)?
Claim 27’s disease list is long and explicitly tethered to plasma kallikrein. The enumerated set includes:
- stroke
- inflammation
- reperfusion injury
- acute myocardial infarction
- deep vein thrombosis
- post fibrinolytic treatment condition
- angina
- edema
- angioedema
- hereditary angioedema
- sepsis
- arthritis
- hemorrhage
- blood loss during cardiopulmonary bypass
- inflammatory bowel disease
- diabetes mellitus
- retinopathy (and multiple retinal diabetes-related entities)
- diabetic macular edema/macular degeneration
- age-related macular edema/macular degeneration
- proliferative retinopathy
- neuropathy
- hypertension
- brain edema
- increased albumin excretion
- macroalbuminuria
- nephropathy
Claim 28 isolates angioedema and Claim 29 isolates hereditary angioedema. Similar splits repeat under Claim 18-based and Claim 19/24-based dependents (Claims 31-32, 34-35, 37-38).
From a landscape standpoint, the broad list increases the chance that a compound positioned for one indication (e.g., hereditary angioedema) could be asserted across other kallikrein-driven disease studies if those are used in marketing, labeling, or clinical protocols tied to the claimed method.
How enforceable is the patent’s claim architecture (practical scope and design-around paths)?
Strengths
- Genus chemical coverage: Claim 1’s structure definition is wide and includes many substitution classes, heterocycles, and optionality.
- Indication breadth: the disease list in Claim 27 is extensive and includes common clinical target categories for kallikrein biology.
- Multiple entry points: dependent claims fix specific substituent sets, enantiomers, salt forms, and therapeutic embodiments. This creates multiple “infringement landing zones.”
Design-around levers
- Chemical structure escape: a competitor can attempt to select a compound outside the Formula II variable boundaries (X/Y/Z/R1c/R2/R3/R3a/R4).
- Salt strategy: using a non-covered salt may avoid salt-dependent claims, but not necessarily Claim 1 if the free base compound is within Formula II.
- Stereochemistry: if an issued dependent claim is limited to (+) or (−), a competitor may attempt to use the opposite enantiomer; however Claim 1 already covers mixtures, and thus full avoidance of Claim 1 requires structural exclusion from Formula II rather than stereochemical inversion alone.
Patent landscape: what this implies for competitive freedom-to-operate
You provided the claim text but not bibliographic metadata (assignee, publication numbers, filing date, related continuations, granted status dates) and no cited references or prosecution history. Without those, a complete US patent landscape map (family members, continuations, related WO filings, and cross-citations) cannot be accurately constructed from the information in this prompt alone.
Given the claim content alone, the landscape conclusions that can be stated with high confidence are structural rather than bibliographic:
- The patent creates a method-of-treatment barrier tied to plasma kallikrein biology using Formula II compound administration.
- Any competitor with a plasma kallikrein program using structurally close chemistry risks falling within Claim 1 even if the target indication differs from angioedema, because Claim 27 enumerates multiple diseases.
- The presence of enantiomer and salt dependents means a competitor also faces risk if they develop the same stereoisomeric or salt form.
Key Takeaways
- US 10,689,346 Claim 1 is a broad method-of-treatment claim covering administration of Formula II compounds (and salts) for diseases “characterized by unwanted plasma kallikrein activity.”
- Chemical scope is driven by Markush variables: X, Y-R4, Z, R1c, R2, R3/R3a, and R4, with optionality across substituents and heterocycles.
- Dependent claims narrow to specific substituent patterns, specific X fragments, specific R3a positional substitution, specific Z halogen/cycloalkyl substitutions, plus enantiomers and hydrochloride/bis(hydrochloride) salts.
- Indication scope in Claim 27 is broad and includes angioedema/hereditary angioedema, plus multiple inflammatory vascular injury and metabolic/renal/ocular conditions.
- The enforcement model is chemistry-first with indication hooks, so design-around requires structural exclusion from Formula II, not just switching salt or enantiomer.
FAQs
1) Does Claim 1 require a specific route of administration or dosing regimen?
No. Claim 1 requires administering a therapeutically effective amount but does not specify route or regimen in the provided claim text.
2) Is angioedema explicitly covered?
Yes. Claim 28 (and parallel dependents for later claim roots) specifies angioedema, and Claim 29 specifies hereditary angioedema.
3) Can a competitor avoid liability by using the opposite enantiomer?
Dependent claims separately mention (+) and (−), but Claim 1 covers mixtures of R/S configurations. Avoiding the dependents may not avoid Claim 1 if the compound remains within Formula II.
4) Are hydrochloride and bis(hydrochloride) salts required for coverage?
No for Claim 1. The salt types appear in dependent claims; Claim 1 covers pharmaceutically acceptable salts generally, with specific hydrochloride embodiments in the dependent claims.
5) What is the main practical risk for an alternative plasma kallikrein compound?
If the alternative compound falls within the extensive Formula II variable definitions, using it to treat any of the listed kallikrein-associated diseases can trigger infringement under the method claim framework.
References
[1] United States Patent 10,689,346, Claims 1-38 (text provided in prompt).
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