Details for Patent: 9,498,465

Which drugs does patent 9,498,465 protect, and when does it expire?

Patent 9,498,465 protects AKLIEF and is included in one NDA.

This patent has eleven patent family members in eleven countries.

Summary for Patent: 9,498,465

Title:	Topical compositions in the form of a gel containing a particular solubilized retinoid
Abstract:	A composition in the form of a gel, preferably hydroglycolic, is described. The composition can include in a physiologically acceptable medium, at least one particular retinoid. Also described, is a method for the preparation thereof and the cosmetic and dermatological use of the same.
Inventor(s):	Agnès Duprat, Claire Mallard
Assignee:	Galderma Research and Development SNC
Application Number:	US14/404,913
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,498,465
Patent Claim Types: see list of patent claims	Use; Composition;

Patent 9,498,465 (US9498465) Scope, Claims, and U.S. Patent Landscape for Formula (I) + Hydrophilic Gel Compositions

US 9,498,465 is a U.S. composition-of-matter and formulation patent built around (1) a broad Markush structure for “compound of general formula (I)” defined by multiple variable substituents, and (2) a topical, gel-style composition defined by solubility in specified hydrophilic solvent/cosolvent systems plus gelling agent and ingredient ranges. The independent claim is directed to a pharmaceutical composition containing a compound of formula (I) plus water, at least one gelling agent, at least one hydrophilic solvent and at least one hydrophilic cosolvent selected to ensure solubility of the compound, with an explicit solvent species list. Dependent claims substantially narrow to a specific active compound (3″-tert-butyl-4′-(2-hydroxyethoxy)-4″-pyrrolidin-1-yl[1,1′;3′,1″]terphenyl-4-carboxylic acid), to an aqueous-glycolic gel, to defined classes and examples of gelling agents (including xanthan gum and specific polymer/cellulose/carrageenan categories), and to drug-product performance metrics tied to dermal/epidermal absorption windows.

The therapeutic method claims are drafted broadly across dermatology indications (acne, inflammatory immunoallergic dermatoses, UV aging, precancer/cancerous cutaneous conditions, etc.) and then narrowed by dependent claim sets to specific disease subsets.

Because the independent claim is anchored to a topical formulation concept (solubilizing formula (I) into specific hydrophilic solvent/cosolvent systems in a gel matrix), the effective “attack surface” for competitors is not only whether they use the same formula (I) compound, but also whether their formulation (solvent/cosolvent selection, gel matrix, and solubility requirement) stays outside the claim language.

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What does US 9,498,465 claim, and how broad is “general formula (I)” in the independent composition claim?

Short answer: Claim 1 covers topical pharmaceutical compositions containing any compound falling within a multi-parameter Markush definition of formula (I), provided the compound is formulated in a gel with water, a gelling agent, and specific hydrophilic solvent/cosolvent systems that solubilize the compound.

Claim-1 architecture (what must all be present)

Claim 1 requires, at minimum:

1. A pharmaceutical composition.
2. An active agent defined as “at least one compound of general formula (I)” with multiple variable positions and linkages.
3. Water.
4. At least one gelling agent.
5. At least one hydrophilic solvent and at least one hydrophilic cosolvent.
6. Solubility condition: “the compound of formula (I) is soluble in the hydrophilic solvent and the hydrophilic cosolvent.”
7. Hydrophilic solvent is selected from: methylpyrrolidone, ethoxydiglycol, benzyl alcohol, polyethylene glycol, phenoxyethanol, ethanol, or mixtures.

Separately, the independent claim provides a full structural description of formula (I) through nested definitions for R1, R2, R3, R4, R5, A, X, Ar, Y, n, R6, and R7/R7′.

Markush breadth by substituent position (claim-feature mapping)

The practical scope depends on how many distinct chemotypes are admitted by each substituent variable. Claim 1 is unusually broad because it uses ranges of alkyl/alkoxy sizes and alternate ring-closure options.

Key breadth points:

• R1: H, C1–C4 alkyl, or CF3.
• R2: H, C1–C4 alkyl or alkoxy, or Cl.
• R3: H or linear/branched C1–C10 alkyl/alkoxy optionally substituted with methoxy.
• R4 and R5: individually H or C1–C3 alkyl, or else together with the —N—C(═Y)— bond form rings including pyrrolidine, pyrrolidinone, piperidine, piperidinone.
• Y: two H atoms or a heteroatom (and dependent claim 32 later restricts Y to O or S).
• Ar: four aromatic ring options: 1,4-phenyl, 2,5-pyridyl, 5,2-pyridyl, or 2,5-thiophenyl.
• X: either C–C single bond or oxygen, with oxygen optionally substituted with an alkyl/alkylamine chain.
• A: hydrogen or a specific additional structural formula (defined in the claim as a substituted fragment with Q).
• Q: oxygen or the —NH— bond.
• R6: H, alkyl C1–C6, cycloalkyl C3–C6, or acyl-type substitutions —C(O)CH2 and —C(O)CH2CH3.
• R7 and R7′: independently H or OH but not simultaneously OH.
• n: 0–5.

Outcome: The independent claim is not limited to one compound. It reads on a family of topically deliverable small molecules with defined aromatic cores and variable substituent chemistry, combined with a gel formulation solubilizing requirement.

What the compound embodiment in claim 3 tells you about likely target chemistry

Dependent claim 3 fixes a single compound name:

3″-tert-butyl-4′-(2-hydroxyethoxy)-4″-pyrrolidin-1-yl[1,1′;3′,1″]terphenyl-4-carboxylic acid

That specificity is important because (a) it confirms the formula (I) family includes this compound, and (b) later claims can pin down formulation ranges and absorption outcomes for this particular active. Competitors often design around by either using a different compound outside the Markush envelope or a different formulation space (solvent/cosolvent and gel matrix choices) that avoids the claim constraints.

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Which formulation elements of the gel are actually doing the work in claim 1?

Short answer: The formulation restrictions that matter most for infringement leverage are the solvent/cosolvent list and the solubility requirement, not just the presence of a gelling agent.

Hydrophilic solvent selection in claim 1

Claim 1’s solvent limitation is explicit:

• methylpyrrolidone
• ethoxydiglycol
• benzyl alcohol
• polyethylene glycol
• phenoxyethanol
• ethanol
• mixtures

This is a concrete constraint. If a competitor’s product uses a solvent system outside this list (and does not rely on one of these as the “hydrophilic solvent” component as claimed), they may avoid claim 1 even if they use a formula (I) compound.

Cosolvent is broader

Claim 1 requires at least one “hydrophilic cosolvent” but does not list cosolvent species in the independent claim. Dependent claim 7 tightens the cosolvent to “a glycol” and claim 18 narrows glycol options to propylene glycol and dipropylene glycol (or mixtures).

Solubility is a claim condition

Claim 1 states that the formula (I) compound is “soluble in the hydrophilic solvent and hydrophilic cosolvent.”

In litigation, that phrase can become a technical battleground: whether solubility is met in the finished formulation, and whether the relevant solvent/cosolvent system in an accused gel truly dissolves the active in the claimed sense.

“Gel-ness” is supported by multiple dependent claims

Claim 4 specifies an “aqueous-glycolic gel.” Claims 5 and 14 detail gelling-agent classes and examples.

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What do claims 4 to 21 protect: aqueous-glycolic gel, gelling agents, and typical cosmetic/pharma additive suites?

Short answer: The dependent claims expand claim 1 into a detailed gel recipe space, including gelling agent categories and a broad “optional additives” menu.

Claim 4: aqueous-glycolic gel

• “an aqueous-glycolic gel in which the active agent is solubilized.”

This reinforces the claim strategy: solubilize the active within an aqueous gel using glycol-based cosolvent.

Claim 5: gelling agent categories

Gelling agent is selected from broad natural and synthetic polymer categories:

• polymers of vegetable origin
• gums
• pectins
• cellulose
• polymers of microbiological origin
• gelling polymers of synthetic origin

Claim 13: microbiological polymer example

• xanthan gum.

Claims 14 to 17: specific gelling polymer embodiments

Claim 14 lists detailed synthetics and mixed systems, including:

• acrylate/C10-30 alkyl acrylate crosspolymers
• polyacrylamides
• polyacrylamide/isoparaffin C13-14/laureth-7 mixtures
• carbomers
• polysaccharides
• aluminum magnesium silicates
• acrylic polymers coupled to hydrophobic chains
• modified starches
• carrageenans

Claim 15 provides a specific polyacrylamide blend:

• sodium acrylamide/acryloyldimethyl taurate copolymer/isohexadecane/polysorbate 80

Claim 16 defines polysaccharides including:

• xanthan gum, gellan gum, guar gum, cellulose

Claim 17 provides cellulose species including:

• microcrystalline cellulose
• sodium carboxymethylcellulose
• hydroxypropylmethylcellulose
• hydroxyethylcellulose

Claim 6 and 7: solvent/cosolvent narrowing

• Claim 6: hydrophilic solvent is phenoxyethanol and/or ethanol.
• Claim 7: cosolvent is a glycol.
• Claim 18: glycol is propylene glycol and/or dipropylene glycol.

Together these dependent claims align the patent with a common topical solvent system (phenoxyethanol or ethanol) and glycol cosolvent.

Claim 8 and 19 to 25: optional additives

Claim 8 allows “one or more additives” from categories:

• preserving agents
• agents improving properties on application
• chelating agents
• antioxidants
• soothing agents and/or anti-irritants

Dependent claims then enumerate examples.

Representative lists:

• Preserving agents include methyl paraben, propyl paraben, benzalkonium chloride, phenoxyethanol, benzyl alcohol, potassium sorbate, benzoic acid, 2-bromo-2-nitropropane-1,3-diol, chlorhexidine, chlorocresol, ethyl alcohol, diazolidinylurea (claim 19).
• Agents improving properties include cyclomethicone or dimethicone (claim 20).
• Chelators include EDTA and salts, dihydroglycerol, citric acid, tartaric acid, gluconolactone (claim 21).
• Antioxidants include vitamin E and vitamin C (claims 22 to 24).
• Soothing/anti-irritants include PPG-12/SMDI copolymer, glycyrrhetinic acid, hyaluronic acid (and sodium hyaluronate), allantoin (claim 25).

These dependent claims can matter in manufacturing differentiation only if an accused product argues it does not include at least one additive category required by the asserted dependent claim. Since claim 8 frames additives as “one or more” and the claim is optional, infringement hinges on the specific dependent claim asserted.

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What is the quantitative product-range coverage in claims 9, 26 to 31, and how does it affect design-around?

Short answer: The patent has explicit concentration windows for the specific active, gelling agent, hydrophilic solvent, cosolvent, and additives. If an accused gel uses different weight percentages outside these ranges, it can avoid those narrower dependent claims, though claim 1 may still capture the formulation if those dependent-range limitations are not asserted.

Claim 9: ingredient ranges for a formula (I) embodiment

• 0.00001% to 1% by weight of the specific active (as written in claim 9)
• water
• 0.005% to 10% gelling agent
• 0.2% to 50% hydrophilic solvent
• 2% to 50% cosolvent
• optionally 0% to 15% additives

Claim 26 and 27: tighter active amount band

• claim 26: 0.0001% to 0.1%
• claim 27: 0.001% to 0.1%

Claim 28 to 31: narrower formulation component ranges

• gelling agent: 1% to 4% (claim 28)
• hydrophilic solvent: 0.5% to 30% (claim 29)
• cosolvent: 10% to 40% (claim 30)
• additives: 0.1% to 10% (claim 31)

Design-around logic: If a competitor targets a different solvent/cosolvent system (outside claim 1’s solvent list), they avoid claim 1 regardless of percentage. If they stay within the solvent list and glycol cosolvent, changing the weight ranges may avoid specific dependent claims but not necessarily claim 1.

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What do claims 10 and 11 protect: absorption/skin deposition targets as a claim limitation?

Short answer: The patent includes performance window claims tied to dermal/epidermal absorption at 16 hours and an epidermal maximum within 1–6 hours. These are process-adjacent product-performance limitations.

• Claim 10: maximum amount absorbed in dermis and epidermis 16 hours after application: 5 to 15 ng/cm².
• Claim 11: maximum amount absorbed in epidermis is obtained 1 to 6 hours after application.

Implication for litigation: These claims shift infringement into comparative pharmaceutics. An accused product that produces different absorption kinetics or deposition values can avoid these dependent claims even when other formulation features match.

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What method-of-use territory does US 9,498,465 cover, and what are the main indication clusters?

Short answer: The method claims cover a wide swath of dermatology and skin disease, including acne, inflammatory dermatoses, UV/photo aging, infections/warts, autoimmune/immune dermatoses, atrophy and healing disorders, fungal conditions, pigmentation disorders, and precancer/cancer conditions. Dependent claims then list specific diseases.

Claim 37: very broad dermatology conditions (clustered)

Examples explicitly listed:

• Acne spectrum: common, comedonal, polymorphic, rosacea, nodulocystic, conglobata, senile, secondary acne.
• Ichthyosis/keratinization and epidermal disorders: ichthyosis, lamellar ichthyosis, Darier’s disease, palmoplantar keratoderma, leukoplakia, pityriasis rubra pilaris.
• Lichen conditions: cutaneous or mucosal lichen (buccal).
• Inflammatory immunoallergic dermatoses and conditions with inflammatory immunoallergic component with or without cell proliferation disorder.
• UV radiation-induced and aging conditions: photo-induced or chronological aging, actinic keratoses, pigmentations.
• Viral warts/papillomatoses: common warts, flat warts, molluscum contagiosum, epidermodysplasia verruciformis, oral or florid papillomatoses.
• Immune dermatoses.
• Corticosteroid-induced atrophy and other atrophy.
• Healing disorders, stretch marks, repair, promoting healing.
• Fungal cutaneous conditions.
• Pigmentation disorders.
• Cutaneous or mucosal cancerous or precancerous conditions.

Claim 38: inflammatory immunoallergic examples

• psoriasis (cutaneous, mucosal), psoriatic arthritis, atopic dermatitis, eczema.

Claims 39–45: aging, lupus, scleroderma, fungal, pigmentation, precancer/cancer list

• claim 39: xerosis, pigmentations, wrinkles
• claim 40: lupus erythematosus
• claim 41: scleroderma
• claim 42: tinea pedis or tinea versicolor
• claim 43: hyperpigmentation, melasma, hypopigmentation, vitiligo
• claim 44: actinic keratoses, Bowen’s disease, in situ carcinomas, keratoacanthomas, basal cell carcinoma, squamous cell carcinoma, cutaneous lymphomas
• claim 45: “T lymphoma”

Claim 46: immune dermatoses and collagen diseases cluster

• lupus erythematosus, bullous immune diseases, collagen diseases.

Claim 47: secondary acne subtypes

• solar acne, acne medicamentosa, occupational acne.

Scope note: These method claims extend beyond formulation ingredients. Even if a competitor designs a composition that avoids claim 1 by solvent/cosolvent differences, method infringement can still be argued if the accused product contains a compound of formula (I) and is used for covered indications (subject to enforcement theory and proof standards).

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How do claim 2 and claim 32 narrow/define the compound family for infringement purposes?

Claim 2: narrower Markush for R1–R5 and A/R6

Claim 2 limits formula (I) parameters, including:

• R1: hydrogen, t-butyl, i-propyl
• R2: hydrogen, t-butyl, i-propyl
• R3: hydrogen or ethyl
• R4 and R5: methyl or ethyl, or together form pyrrolidine ring
• A and R6 options constrained to listed substituents including H, i-propyl, t-butyl, cycloalkyl C3–C6, or —C(O)CH2 / —C(O)CH2CH3

This dependent claim is still broad in practice but narrows relative to claim 1.

Claim 32: Y is O or S

Claim 32 limits Y to heteroatoms O or S.

Claim 33 to 36: additional narrowing of gelling agents and starch/carrageenan families

• claim 33: PEG-150/decyl/SMDI copolymer
• claim 34: modified potato starch
• claim 35: carrageenan families κ, λ, β, ω
• claim 36 repeats cellulose selection set.

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Where the patent stands in the U.S. landscape for 9,498,465: what can be inferred from claim scope, without relying on external listing data

A claim set like this typically indicates the following enforceable “layers” in the U.S. landscape:

1. Compound-family + formulation solubility into specific hydrophilic solvent list (independent claim 1).
2. A product recipe layer for an aqueous-glycolic gel with defined gelling agents and optional dermatology additive categories (claims 4–8, 13–21).
3. Specific active and concentration ranges (claims 3, 9, 26–31).
4. Performance/absorption window limitations (claims 10 and 11).
5. Indication layer that can capture use for a broad set of dermatology conditions (claims 37–47).

For a U.S. generic or biosimilar-like challenge scenario (if applicable), the typical infringement pathway is:

• determine whether the ANDA (or other submission) proposes a product containing a formula (I) compound;
• then determine whether the formulation uses a hydrophilic solvent within the claim-1 list and a hydrophilic cosolvent satisfying the solubility requirement;
• finally evaluate whether the specific dependent claims (gel type, gelling agent class, ranges, and absorption kinetics) align.

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Key Takeaways

• US 9,498,465’s core protection is formulation-specific: it covers a topical gel composition containing a formula (I) active, with water + gelling agent + hydrophilic solvent (from a listed set) + hydrophilic cosolvent, where the active is soluble in the solvent/cosolvent system.
• The chemical scope is Markush-broad: multiple substitution and ring options (including cyclization to pyrrolidine/piperidine-type rings) support a family-level claim strategy.
• Dependent claims narrow to a specific active and gel recipe: the named active compound appears in dependent claims with explicit concentration ranges and absorption window limitations.
• Method claims cover wide dermatology indications: acne, immune dermatoses, UV/photo aging, fungal conditions, pigmentation disorders, and certain precancer/cancer skin indications.
• Design-around hinges on two levers: (1) staying outside the formula (I) compound family, and/or (2) using a solvent/cosolvent system that avoids claim-1’s hydrophilic solvent list and the solubility-defined formulation requirement; range and absorption claims add further narrowing only if those dependent claims are asserted.

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FAQs

1) What solvent substitutions are most likely to avoid claim 1 of US 9,498,465?
A hydrophilic solvent system that does not use methylpyrrolidone, ethoxydiglycol, benzyl alcohol, polyethylene glycol, phenoxyethanol, or ethanol (as the “hydrophilic solvent” component) is the most direct route to avoid the independent claim.

2) Does claim 1 require the use of glycol as the cosolvent?
Claim 1 requires a hydrophilic cosolvent but does not require glycol in the independent claim. The glycol requirement appears in dependent claim 7, and specific glycol species appear in dependent claim 18.

3) Can a competitor avoid claims 10 and 11 without changing the chemical identity of the active?
Yes. Those claims are limited by measured absorption/skin deposition windows (16-hour dermis/epidermis and 1–6 hour epidermal maximum). A different formulation or dosing profile that changes absorption kinetics can fall outside those dependent claims.

4) How important is the specific named active compound in the overall patent value?
It is critical for the narrower dependent claims (claims 3, 9, 26–31, and the concentration-performance claims). The independent claim can still be infringed by other formula (I) compounds if the solubility-and-solvent requirements are met.

5) Do the method claims depend on the exact gel formulation?
They depend on administering “the composition as claimed in claim 1,” so in enforcement they connect back to the claim-1 formulation concept (compound of formula I in the defined gel system).

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References

No external sources were provided with the prompt, and none are cited from external patent databases.

Drugs Protected by US Patent 9,498,465

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Galderma Labs Lp	AKLIEF	trifarotene	CREAM;TOPICAL	211527-001	Oct 4, 2019		RX	Yes	Yes			Y			TOPICAL TREATMENT OF ACNE VULGARIS

Foreign Priority and PCT Information for Patent: 9,498,465

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	12 55092	Jun 1, 2012

PCT Information
PCT Filed	May 30, 2013	PCT Application Number:	PCT/EP2013/061200
PCT Publication Date:	December 05, 2013	PCT Publication Number:	WO2013/178759

International Family Members for US Patent 9,498,465

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013269582
Brazil	112014029879
Canada	2874270
China	104507471