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Patent landscape, scope, and claims: |
United States Patent 9,359,399: What Is Claimed, What It Covers, and How to Read the KOR-Pruritus Landscape
US Patent 9,359,399 (assignee not provided) claims a method of treating pruritus and other kappa opioid receptor-associated diseases/conditions in mammals using a synthetic peptide amide defined by a multi-parameter structure set (Xaa1-Xaa4 and a heterocycle “moiety” with variable linker and ring substitution constraints). The claims are structured to cover:
- Broad indication coverage for pruritus phenotypes (atopic dermatitis, dialysis-associated, ocular, otic, insect bite, opioid-induced, cholestasis variants, malignancy-associated, anemia, jaundice, and a range of dermato-inflammatory and other conditions).
- Broad chemistry coverage via a Markush-style combinatorial scaffold controlling stereochemistry and side-chain substitutions, including explicit “negative” exclusions tied to specific combinations of residues.
- Specific sub-species coverage via dependent claim narrowing to defined residue sets and to a single exemplified compound (Compound (2): D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH).
Where the Claim Starts: Method-of-Treatment With a Kappa Opioid Receptor Hook
Independent claim 1 is a treatment method. It requires:
- A kappa opioid receptor-associated disease/condition in a mammal.
- That the disease/condition is pruritis.
- Administration of a composition containing an effective amount of a synthetic peptide amide with:
- a defined peptide core: Xaa1, Xaa2, Xaa3, Xaa4 (each drawn from enumerated stereochemical and substitution sets), and
- a terminal “moiety” that includes a heterocyclic ring motif and variable attachment elements including W, Y, Z, V, e, plus an R1/R2 substituent framework with constraints on aromaticity, attachment position, spiro and fused options, and “not both H” style conditions for certain ring states, and
- optional forms including salts, hydrates, acid salts, N-oxides, and stereoisomer mixtures.
Even though the chemical expression is complex, the legal effect is straightforward: any synthetic peptide amide meeting the enumerated structural parameters for Xaa1-Xaa4 and the heterocycle/terminal moiety falls within the claim’s method coverage if used to treat KOR-associated pruritus.
What the Independent Claim Covers Chemically (Xaa1-Xaa4 and the Terminal Moiety)
Claim 1 defines the peptide amide using four residue positions plus a terminal heterocycle-containing moiety.
Residue position set (Xaa1)
Xaa1 is selected from:
- (A)(A′)D-Phe
- (A)(A′)(α-Me)D-Phe
- D-Tyr
- D-Tic
- D-tert-leucine
- D-neopentylglycine
- D-phenylglycine
- D-homophenylalanine
- β-(E)D-Ala
With ring substituents:
- Each (A) and each (A′) is independently H, F, Cl, NO2, CH3, CF3, CN, or CONH2
- Each (E) is independently cyclobutyl, cyclopentyl, cyclohexyl, pyridyl, thienyl, thiazolyl
Residue position set (Xaa2)
Xaa2 is selected from:
- (A)(A′)D-Phe
- 3,4-dichloro-D-Phe
- (A)(A′)(α-Me)D-Phe
- D-1Nal
- D-2Nal
- D-Tyr
- (E)D-Ala
- D-Trp
Residue position set (Xaa3)
Xaa3 is selected from:
- D-Nle
- D-Phe
- (E)D-Ala
- D-Leu
- (α-Me)D-Leu
- D-Hle
- D-Val
- D-Met
Residue position set (Xaa4)
Xaa4 is selected from a wide set of cationic and amidinyl/guanidinyl-like side-chain analogs including:
- (B)2D-Arg
- (B)2D-Nar
- (B)2D-Har
- ζ-(B)D-Hlys
- D-Dap
- ε-(B)D-Lys
- ε-(B)2-D-Lys
- D-Amf
- amidino-D-Amf
- γ-(B)2D-Dbu
- δ-(B)2α-(B′)D-Orn
- multiple amidino- or guanidino-substituted amino acids
- multiple amino group stereochemical variants (cis/trans and piperidine/aminopyrrolidine substituted variants)
Where:
- (B) is independently H or C1-C4 alkyl
- (B′) is H or (α-Me)
Terminal moiety and heterocycle framework
Claim 1 also defines a heterocyclic ring motif with parameters:
-
W is selected from multiple connector states:
- Null, with a condition that when W is null, Y is N
- —NH—(CH2)b— where b = 0..6
- —NH—(CH2)c—O— where c = 2 or 3
- and the condition that when W is of the latter type, Y is C
-
The “moiety” is an optionally substituted 4 to 8-membered heterocyclic ring moiety with:
- ring heteroatoms all N
- Y and Z each independently C or N
- if 6, 7, or 8-membered: Y and Z are separated by at least two ring atoms
- if the ring has a single N heteroatom: ring is non-aromatic
-
V is C1-C6 alkyl
-
e is 0 or 1
- if e = 0, V is null and R1 and R2 are directly bonded to the same or different ring atoms
-
R1 and R2 are each independently from broad functional groups including:
- H, OH, halo, CF3, NH2, COOH, C1-C6 alkyl, C1-C6 alkoxy,
- amidino and substituted amidino,
- aryl and optionally substituted heterocyclyl,
- Pro-amide, Pro, Gly, Ala, Val, Leu, Lys, Arg, Orn, Ser, Thr,
- CN, CONH2, COR′, sulfonamides, carbamates, etc.
And R1/R2 can be combined to form ring systems:
- (i) R1 and R2 independently with restrictions (including “not —OH” and “not both —H” constraints for certain Y/Z ring states)
- (ii) R1 and R2 together can form an optionally substituted 4 to 9-membered heterocyclic monocyclic or bicyclic ring bonded to the Y/Z-containing ring
- (iii) R1 and R2 plus one ring atom can form an optionally substituted 4 to 8-membered spiro structure
- (iv) R1 and R2 plus two or more adjacent ring atoms can form an optionally substituted 4 to 9-membered fused monocyclic or bicyclic ring to the Y/Z-containing ring
And there are explicit positional constraints for a six-membered, two-heteroatom scenario:
- if Y and Z are N and W is null, then —(V)eR1R2 is attached to a ring atom other than Z
- if e is zero, then R1 and R2 are not both H
Exclusions encoded into the claim
Claim 1 has explicit “not this combination” rules:
- If Xaa3 is D-Nle, then Xaa4 is not (B)2D-Arg
- If Xaa3 is D-Leu or (αMe)D-Leu, then Xaa4 is not δ-(B)2α-(B′)D-Orn
These exclusions narrow coverage for certain residue pairing combinations even though the overall structure set is very broad.
How the Claims Narrow: Dependent Claims Define Indications and Sub-Species Compounds
Dependent claims 2 through 20 focus on narrowing:
Claim 4 and Compound (2): a concrete exemplified target
- Claim 4: “The method of claim 3 having the structure of Compound (2):
D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH.”
This is a strong anchor in enforcement: the patent covers at least one specific peptide amide structure used for pruritus under the broader genus from claim 1.
Claim 3: a defined residue combination
Claim 3 states:
- Xaa1Xaa2 is D-Phe-D-Phe
- Xaa3 is D-Leu or D-Nle
- Xaa4 is selected from:
- (B)2D-Arg
- D-Lys
- (B)2D-Har
- ζ-(B)D-Hlys
- D-Dap
- ε-(B)D-Lys
- ε-(B)2-D-Lys
- D-Amf
- amidino-D-Amf
- γ-(B)2D-Dbu
- δ-(B)2α-(B′)D-Orn
This dependent claim narrows the claim 1 genus by fixing Xaa1 and Xaa2 and limiting Xaa3 to two possibilities, while keeping Xaa4 broad.
Claim 5 and Claim 6 to 20: pruritus phenotype list
Claim 5 introduces a pruritus sub-selection list. Claims 6 to 20 then assign specific phenotypes:
Claim 5 (pruritus selected from):
- pruritis in atopic dermatitis
- kidney dialysis-associated puritis
- ocular pruritis
- otitic pruritis
- insect bite pruritis
- opioid-induced pruritis
Claim 6 (example branch): atopic dermatitis
Claim 7: kidney-dialysis associated pruritis
Claim 8: uremic pruritis
Claim 9: ocular pruritis
Claim 10: ocular pruritis due to conjunctivitis
Claim 11: otic pruritis
Claim 12: insect bite pruritis
Claim 13: opioid-induced pruritis
Claim 14: opioid-induced pruritis is morphine-induced pruritis
Claim 15: pruritis in cholestasis
Claim 16: cholestasis variants including:
- primary biliary cirrhosis
- intrahepatic cholestasis of pregnancy
- chronic cholestatic liver disease
Claim 17: malignant cholestasis
Claim 18: pruritis in anemia
Claim 19: pruritis associated with jaundice
Claim 20: pruritis associated with conditions including:
- eczema
- psoriasis
- polycythemia vera
- lichen planus
- lichen simplex chronicus
- pediculosis
- thyrotoxicosis
- tinea pedis
- urticaria
- scabies
- vaginitis
- hemorrhoids
Legal read: the claim set is not limited to a single pruritus etiology. It covers multiple clinical buckets, including immune/inflammatory, metabolic, hepatic/biliary, renal, infectious/parasite, and treatment-emergent opioid pruritus.
Claim Scope Map: What Falls Inside vs. What Gets Pushed Out
A practical scope map for freedom-to-operate or competitive assessment:
Inside scope
- Any synthetic peptide amide meeting claim 1’s:
- Xaa1/Xaa2/Xaa3/Xaa4 enumerations and stereochemical/substitution rules,
- terminal moiety heterocycle constraints (Y/Z rules, W connector options, ring aromaticity/non-aromatic constraints),
- R1/R2 ring-forming constraints and substitution menus,
- plus the explicit exclusion combos already built into claim 1,
- used in a method of treating pruritus as defined by the disease/condition selection (claim 1) and the phenotype lists (claims 5 to 20).
Outside scope (by claim text)
- Any treatment method for kappa opioid receptor-associated disease/conditions other than pruritis would not satisfy claim 1 as written.
- Any formulation that fails structural matching of claim 1’s peptide amide scaffold parameters is out.
- Any scaffold that matches the genus but uses a prohibited combination such as:
- Xaa3 = D-Nle with Xaa4 = (B)2D-Arg
- Xaa3 = D-Leu or (αMe)D-Leu with Xaa4 = δ-(B)2α-(B′)D-Orn
is out for claim 1.
Patent Landscape Strategy: How 9,359,399 Positions Itself in KOR-Pruritus
Within the kappa opioid receptor (KOR) pruritus field, patents like 9,359,399 are typically deployed in one or more ways: (1) as composition-activity anchors, (2) as method claim coverage across multiple pruritus etiologies, and (3) as structural-genus blockers with explicit exemplified sub-species.
Based on the claim architecture, 9,359,399 behaves like a genus-plus-pruritus-phenotype patent:
- Genus chemistry coverage: broad Markush selections for multiple residue types plus a flexible terminal heterocycle/connector framework.
- Phenotype coverage: multiple clinical pruritus variants in dependent claims, enabling:
- claim-by-claim enforceability against product labels that target specific indications, and
- prosecution or litigation arguments that pruritus is a consistent disease/condition class tied to KOR activity rather than a single etiologic niche.
Key competitive implications
- A competitor developing a KOR-targeting peptide amide aimed at pruritus should expect claim-chart exposure on:
- any pruritus label broad enough to match the dependent claim set, and
- any compound whose Xaa1-Xaa4 and terminal moiety can be mapped into the enumerated claim 1 categories.
- Even where a competitor avoids the exemplified Compound (2), the independent claim’s breadth still permits coverage if the competitor lands in any structural combination captured by claim 1.
What to Extract for Claim Charts
For infringement analysis, the claim 1 build suggests a claim chart should be organized into these columns:
- Indication element
- Is the asserted disease/condition “pruritis” and is it described as one of the claim 5-20 phenotype categories?
- Peptide core mapping
- Identify the residues corresponding to Xaa1, Xaa2, Xaa3, Xaa4, including stereochemistry and side-chain substitutions.
- Explicit exclusions
- Check the two “not allowed” Xaa3/Xaa4 combinations.
- Terminal moiety mapping
- Determine the heterocycle ring size (4-8 member), heteroatom rules (N-only), Y/Z positions, aromaticity status, and whether the structure is compatible with non-aromatic six/single-N cases.
- Connector parameter W
- Determine whether the linker state matches “Null” vs —NH—(CH2)b— vs —NH—(CH2)c—O— with the corresponding Y condition.
- R1/R2 framework
- Determine whether R1/R2 satisfy the independent substituent sets or the combined ring-forming/spiro/fused constraints.
This approach is more efficient than attempting to map every chemical parameter at once; it targets the claim’s modular logic.
Key Takeaways
- US 9,359,399 claims a KOR-associated pruritus treatment method using synthetic peptide amides defined by a broad structural genus (Xaa1-Xaa4 plus a constrained heterocycle terminal moiety).
- Claim scope is broad on indications: it covers pruritus across multiple etiologies and clinical categories, including atopic dermatitis, dialysis/uremic pruritus, ocular/otic, insect bite, opioid (including morphine-induced), cholestasis subtypes, malignant cholestasis, anemia, jaundice, and a long list of other associated conditions.
- Chemistry coverage is broad but not unlimited: claim 1 includes explicit residue pairing exclusions (D-Nle with (B)2D-Arg; D-Leu/(αMe)D-Leu with δ-(B)2α-(B′)D-Orn).
- Enforcement is supported by a concrete exemplified structure in dependent claim 4: D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH.
- The patent’s best strategic use in the landscape is as a genus-plus-pruritus-phenotype blocker, pushing competitors either toward non-matching peptide/terminal moieties or toward indications outside the claim’s pruritus-defined scope.
FAQs
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Is US 9,359,399 limited to one form of pruritus?
No. The dependent claims list multiple pruritus etiologies and phenotypes (claims 5-20), including atopic dermatitis, dialysis/uremic, ocular/otic, insect bite, opioid-induced (including morphine), cholestasis variants, malignant cholestasis, anemia, jaundice, and numerous other associated conditions.
-
What is the “hard anchor” compound in the claim set?
Dependent claim 4 specifies “Compound (2)” as D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH.
-
Does the independent claim require that the patient has KOR-associated disease?
Yes. Claim 1 requires a kappa opioid receptor-associated disease or condition and then narrows that disease/condition to pruritis.
-
Are there explicit chemical combinations carved out of claim 1?
Yes. Claim 1 includes exclusion rules tied to residue pairing:
- If Xaa3 is D-Nle, Xaa4 is not (B)2D-Arg.
- If Xaa3 is D-Leu or (αMe)D-Leu, Xaa4 is not δ-(B)2α-(B′)D-Orn.
-
How should an infringement analysis be structured for this patent?
Use a modular mapping to claim 1’s components: (1) indication pruritis/phenotype, (2) Xaa1-Xaa4 residues and stereochemistry, (3) the two explicit residue pairing exclusions, and (4) terminal moiety parameters (W, Y/Z, heterocycle size and aromaticity constraints, and R1/R2 rules including possible ring/spiro/fused options).
References (APA)
- US Patent 9,359,399, claims as provided in the prompt.
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