Scope and claims analysis for US Patent 9,422,299 (Formula I neurokinin-3 receptor inhibitors) and the United States IP landscape

US Patent 9,422,299 is a broad, structure-defining US compound and use patent built around “Formula I” neurokinin-3 receptor (NK3R) inhibitors. The claims are drafted in a layered manner: (i) Markush-style compound genus with extensive substituent permissiveness and (R)-selectivity, (ii) nested dependent species sub-formulas, (iii) express enumerated examples, (iv) pharmaceutical composition and medicament claims, and (v) method-of-use claims tied to NK3R activity inhibition and a wide therapeutics list (with special dependent specificity for multiple disease areas).

What is US Patent 9,422,299’s claimed core: Formula I NK3R inhibitors?

Bottom line: The patent’s infringement hook is the compound definition of Formula I covering a large chemical genus, with structural constraints on heteroatom patterning, aromatic/aryl substitution patterns, and an explicit stereochemical requirement for the (R)-enantiomer or racemate.

How Formula I is constructed (claim 1)

Claim 1 defines a compound of Formula I with the following variable constraints:

R1: H, F or methyl
R1′: H
R2: H, F, Cl or methoxy
R2′: H or F
R3: H, F, Cl, methyl, trifluoromethyl, or cyano
R4: methyl, ethyl, n-propyl, hydroxyethyl, methoxyethyl, trifluoromethyl, difluoromethyl, or fluoromethyl
R5: methyl, ethyl, methoxymethyl, trifluoromethyl, difluoromethyl, or fluoromethyl
Ring/unsaturation and heteroatom pattern:
- X1 and X2: either X1 = N and X2 = S or O, or X1 = S and X2 = N
- “represents a single or a double bond depending on X1 and X2”
Enantiomer status:
- “stands for the (R)-enantiomer or for the racemate”

Interpretation in enforcement terms

Claim 1 is not limited to one drug-like entry. It is an IP moat around a scaffold with multiple allowed substituents.
The X1/X2 rule is a structural gate. An accused compound must fit the thiadiazole/oxadiazole-like connectivity implied by the X1/X2 assignment, or must be mapped into the same constitutional framework.
The stereochemistry clause (“(R)-enantiomer or racemate”) expands coverage beyond a single enantiomer manufacturing outcome.

How claim 15 tightens the variable set for R5

Claim 15 defines a second Formula I variation where R5 is restricted to:

1-fluoroethyl, 1,1-difluoroethyl, or 2,2,2-trifluoroethyl

This is a meaningful claim-layering tactic:

It creates a sub-genus with a narrower R5 set, often used in dependent species fallbacks and in design-around targeting (for example, changing the R5 substituent from fluorinated ethyl-like groups to methyl/ethyl/methoxymethyl-like groups).

Which dependent claims narrow Formula I into specific sub-formulas and how?

Formula I′ (claim 2)

Claim 2 recites a compound of Formula I′, dependent on claim 1. Without the patent’s diagrammatic detail, the practical value for scope is that it creates a second scaffold label likely corresponding to a particular ring unsaturation state or a particular positional isomer within the same Markush framework.

Nested “Ia / Ia′ / Ia″ / Ia-1 / Ia-2 / Ia-3 / Ib / Ib′ / Ic / Ic′” (claims 3 to 11)

The dependent claim family appears to split Formula I into regionally defined substituent corridors:

Claim 3: Formula Ia
- Same R1′ = H, R2′ = H/F, X pattern preserved
- R4 and R5 remain broadly permissive (R4 includes hydroxyethyl and multiple C1-C2/CX groups; R5 includes methyl/ethyl/methoxymethyl plus fluorinated groups)
- Enforces (R) or racemate
Claim 4: Formula Ia′ or Ia″
- Adds split variants while keeping the same overall R1/R1′/R2/R2′/R3/R4/R5 permissible sets.
Claim 5: Formula Ia-1
- Narrows R3 to: H, F, Cl, methyl, trifluoromethyl, cyano
- Narrows the levers to specific allowed R3 set, which is a classic strategy to capture key commercial candidates while still retaining genus reach.
Claim 6: Formula Ia-2
- Narrows R4 away from hydroxyethyl and methoxyethyl variants (R4 is absent in the claim text you provided for R4 in claim 6 snippet, implying the dependent formula likely changes which substituent position is active). It still controls R1/R2/R3/R5.
Claim 7: Formula Ia-3
- Keeps R3 permissive and retains R4 as in claim 3 (including hydroxyethyl and fluorinated methylene-like groups)
Claim 8: Formula Ib
- Forces R3 = F
- Limits R5 to methyl/ethyl/trifluoromethyl/difluoromethyl/fluoromethyl
- Keeps (R) or racemate
Claim 9: Formula Ib′
- Like claim 8, but only explicitly recites R3 = F and R5 set
Claim 10: Formula Ic
- R4 narrowed to methyl/ethyl/n-propyl/hydroxyethyl
- R5 narrowed to methyl/ethyl/trifluoromethyl
- R1/R2/R3 remain permissive under the Ic list
Claim 11: Formula Ic′
- Like claim 10 but removes some substituents (R5 is methyl/ethyl/trifluoromethyl)

Scope consequence

If an accused compound’s substitution pattern matches any nested corridor, it can fall into a dependent claim without requiring perfect fit to the widest Markush genus.
Those narrowings are frequently used for claim differentiation in litigation: even if the widest genus is challenged, narrower corridors can remain in force.

What species are expressly enumerated and how many “anchor compounds” are covered?

Enumerated group compounds (claim 12 and claim 13)

Claim 12 lists a large set of specific (R)-enantiomer compounds (and in some entries the “R” appears explicitly at the molecule level). The list is long and includes many variations in aryl ring substitution and heteroaryl ring substitution (notably 1,2,4-thiadiazol-5-yl and 1,2,4-oxadiazol-5-yl motifs, plus multiple substituted phenyl or benzene nitrile-like aryl caps).

From the text provided, claim 12 includes, among others:

(R)-(3,4-dichlorophenyl) (8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-...-yl)methanone
(R)-(4-fluorophenyl) (8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-...-yl)methanone
(R)-(8-(2-hydroxyethyl)-... ) (4-fluorophenyl)methanone
(R)-(3-(3-ethyl-1,2,4-oxadiazol-5-yl)-... ) (4-fluorophenyl)methanone
(R)-(4-(8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-...tetrahydro...) (benzonitrile))…

Claim 13 then lists a smaller subset of those enumerated compounds, including:

(R)-(3-(3-ethyl-1,2,4-thiadiazol-5-yl)-8-methyl-... ) (4-fluorophenyl)methanone
(R)-(4-chlorophenyl) (8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-... )methanone
(R)-(4-fluorophenyl) (8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-... )methanone
(R)-(4-fluorophenyl) (8-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)-... )methanone

A single highlighted species (claim 14)

Claim 14 isolates:

(R)-(4-fluorophenyl) (8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone

Enforcement value

Enumerated species provide cleaner infringement pathways than broad genus attacks because the accused product can be mapped 1:1 by name-structure.
Species claims also help sustain the patent even if some Markush breadth is attacked as overreaching.

What pharmaceutical composition and medicament claims are asserted?

Composition (claim 18)

A pharmaceutical composition comprising:

a compound of Formula I (as in claim 1)
plus “at least one pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant”

Medicament (claim 19)

A “medicament” comprising the same Formula I compound set.

Scope consequence

These claims typically capture dosage-form labeling and formulation sales even when the active ingredient is sold as a drug product rather than as an intermediate.

What method-of-use claims exist: NK3R inhibition and therapeutic indications?

Core use: inhibit neurokinin-3 receptor activity (claims 20, 30)

Claim 20:

“A method for inhibiting neurokinin-3 receptor activity in a patient”
Administration of an NK3R inhibitor compound of Formula I
The “compound is (R)-enantiomer or racemate” structure constraint remains

Claim 30 is effectively a parallel method claim with the R5 restricted to 1-fluoroethyl / 1,1-difluoroethyl / 2,2,2-trifluoroethyl set.

Indication breadth (claim 21)

Claim 21 lists a broad set of conditions including:

depression, anxiety, psychosis, schizophrenia, psychotic disorders, bipolar disorders
cognitive disorders, Parkinson’s disease, Alzheimer’s disease
ADHD, pain, convulsion
obesity, inflammatory diseases, emesis
pre-eclampsia, airway related diseases, urinary incontinence
reproduction disorders, contraception and sex hormone-dependent diseases

Dependent specificity: sex-hormone dependent diseases (claims 22-24)

Claim 22 enumerates many disorders including:

BPH, prostatic hyperplasia, metastatic prostatic carcinoma
testicular cancer, breast cancer, ovarian cancer
androgen dependent acne, male pattern baldness
endometriosis, abnormal puberty, uterine fibrosis, uterine fibroid tumor, uterine leiomyoma
hyperandrogenism, hirsutism, virilization
PCOS, PMDD, HAIR-AN
ovarian hyperthecosis and “other manifestations of high intraovarian androgen concentrations”
androgen-producing tumor
menorrhagia and adenomyosis

Claim 23 adds “other manifestations” like:

follicular maturation arrest, atresia, anovulation, dysmenorrhea, dysfunctional uterine bleeding, infertility

Claim 24 targets:

virilizing ovarian tumor or virilizing adrenal tumor

Dependent specificity: airway diseases (claim 25)

COPD, asthma, airway hyperresponsiveness, bronchoconstriction, cough

Dependent specificity: inflammatory bowel disorders (claim 26)

irritable bowel syndrome, inflammatory bowel disorder

Hot flashes (claims 28-29)

Claim 28:

patient suffers from hot flashes

Claim 29:

hot flashes with the specific (R)-(4-fluorophenyl) ... thiadiazolyl compound

Practical implication

Method claims are broad on indication. Even if compound scope narrows in later analysis, these dependent indications create a second infringement axis for specific patient populations, dose regimens, and clinical trial claims.

Claim architecture map: what must an accused product do to infringe?

Infringement gates by claim type

Claim type	What must match	Typical design-around lever
Claim 1 (compound genus)	Scaffold in Formula I plus permitted substituents R1-R5 and X1/X2 and stereochemical (R) or racemate	Change any constrained substitution, alter X1/X2 pattern, or shift stereochemistry away from (R) if racemate is not at issue
Dependent formula claims (Ia/Ib/Ic series)	Must also meet narrower corridors (R3 fixed to F, R4/R5 restricted, etc.)	Shift substituents to fall outside each corridor
Claim 12/13/14 (enumerated species)	Exact listed structures	Select an unlisted analog outside enumerated set and outside Markush genus
Claim 18/19 (composition/medicament)	Contains Formula I compound + pharmaceutically acceptable carriers	Formulate a non-infringing compound or use a different active
Claim 20/30 (method)	Administration of infringing compound to inhibit NK3R activity	Non-infringing compound, or different pharmacologic mechanism and non-infringing indication labeling

United States patent landscape: what can and cannot be concluded from the supplied record

Cannot be produced from the information provided. The request requires a “detailed analysis … and patent landscape” (eg, other US patents in the family, priority claims, expiration dates, Orange Book listings, Paragraph IV challenges, litigation dockets, assignees, and current patent status). None of those are present in the material you provided. Producing those would require external bibliographic and legal databases, which are not supplied here.

Key Takeaways

US 9,422,299 is built around a Formula I NK3R inhibitor scaffold with extensive Markush-style substituent coverage and (R)-enantiomer or racemate coverage.
The claim set uses a layered narrowing ladder: genus (claim 1) → nested sub-formulas (claims 3-11) → enumerated species (claims 12-14) → composition (claims 18-19) → NK3R method-of-use (claims 20-30).
Dependent indications are broad and include sex-hormone dependent diseases, airway diseases, inflammatory bowel conditions, and hot flashes, creating multiple infringement targets for clinical and labeling activities.
A meaningful design-around strategy would focus on the claim “gates”: X1/X2 heteroatom connectivity, R1′ and R2′ constraints, R3/R4/R5 allowed sets, and enantiomer status.

FAQs

How do the X1/X2 constraints affect infringement risk under claim 1?
Does US 9,422,299 cover both (R)-enantiomer and racemate, and how does that impact stereochemical design-around?
Which dependent sub-formulas (Ia/Ib/Ic series) are the likely fallback positions if claim 1 breadth is challenged?
How do the enumerated species in claims 12-14 change litigation strategy versus arguing Markush scope?
What is the practical relationship between the composition claims (18-19) and the method claims (20-30) for commercial launch risk?

References

US Patent 9,422,299 (claims as provided in prompt).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astellas	VEOZAH	fezolinetant	TABLET;ORAL	216578-001	May 12, 2023		RX	Yes	Yes	9,422,299	⤷ Start Trial	Y	Y		TREATMENT OF MODERATE TO SEVERE VASOMOTOR SYMPTOMS DUE TO MENOPAUSE	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2948455	⤷ Start Trial	301272	Netherlands	⤷ Start Trial
European Patent Office	2948455	⤷ Start Trial	CA 2024 00017	Denmark	⤷ Start Trial
European Patent Office	2948455	⤷ Start Trial	CR 2024 00017	Denmark	⤷ Start Trial
European Patent Office	2948455	⤷ Start Trial	PA2024513	Lithuania	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,422,299

Which drugs does patent 9,422,299 protect, and when does it expire?

Summary for Patent: 9,422,299