Details for Patent: 9,433,679

Which drugs does patent 9,433,679 protect, and when does it expire?

Patent 9,433,679 protects TRYPTYR and is included in one NDA.

This patent has ten patent family members in four countries.

Summary for Patent: 9,433,679

Title:	Use of TRMP8 for treating opthalmic diseases or conditions involving tearing
Abstract:	The invention relates to therapeutic compositions for the treatment of dry eye, more specifically to compositions comprising a TRPM8 receptor agonist ligand. Furthermore, the invention relates to therapeutic compositions for the treatment of epiphora, more specifically to compositions comprising a TRPM8 receptor antagonist.
Inventor(s):	Carlos Belmonte Martínez, Juana Gallar Martínez, Antonio Ferrer Montiel, Asia Fernández Carvajal, Félix Viana De La Iglesia
Assignee:	Consejo Superior de Investigaciones Cientificas CSIC , Universidad Miguel Hernandez de Elche UMH
Application Number:	US14/699,873
Patent Claim Types: see list of patent claims	Use; Composition;

Scope and patent landscape for US Patent 9,433,679 (TRPM8 ophthalmic therapy): claim boundaries, competitive risk, and likely design-around space

US Patent 9,433,679 protects US method-of-use claims for treating ophthalmic diseases linked to tearing abnormalities and/or relief of tearing-related symptoms using a TRPM8-binding molecule that modulates TRPM8 activity and changes tear secretion, with additional dependent claim narrowing by (1) TRPM8 agonist vs antagonist; (2) specific disease categories (xerophthalmia vs epiphora) and associated subtypes; (3) specific TRPM8 chemotypes (5-methyl-2-isopropyl cyclohexane core) and enumerated example ligands (including WS-12 and menthol-family “cooling” agents); (4) combination regimens with ocular drugs (anti-inflammatory, vitamin A, muscarinic agonists, immunosuppressants, antibiotics); and (5) adjunct formulation elements (lubricants) and dosing frequency. The estate is best read as a platform for TRPM8 agonist/antagonist ocular dosing tied to tear secretion outcomes, with enforceability concentrated in the specific claim themes above rather than broad TRPM8 ophthalmic use unconstrained by mechanism, outcome, and cytotoxicity limitations.

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What does US 9,433,679 claim protect for TRPM8 ophthalmic treatment?

Short answer: A method for treating tear-related ophthalmic diseases by administering a therapeutically effective amount of a composition containing a TRPM8-specific binder that modulates TRPM8 and increases or decreases tear secretion, where the TRPM8 binder is non-cytotoxic, with dependent claim narrowing by agonist/antagonist, disease subtype (xerophthalmia/epiphora), chemotype (5-methyl-2-isopropyl cyclohexane core), named ligands, combination drugs, lubricants, and dosing frequency.

Claim 1 is the anchor: “TRPM8 binder + tear secretion modulation + non-cytotoxicity”

Claim 1 sets the core infringement tripwire:

1. Therapeutically effective amount
2. Ophthalmic disease/condition involving tearing and/or relieving tearing symptoms
3. Composition includes a molecule binding specifically to TRPM8
4. Binding modulates TRPM8 channel activity
5. Binding increases or decreases tear secretion caused by the disease
6. Amount is not cytotoxic

Practical boundary impact

• The claim is outcome-linked to tear secretion (increase/decrease), not just TRPM8 pharmacology in vitro.
• “Binding specifically to TRPM8” and “modulates TRPM8 channel activity” require mechanistic relevance; formulations that deliver TRPM8 activity indirectly without demonstrating specific binding/modulation face higher validity and infringement friction.
• “Not cytotoxic” is a functional limitation that can support argumentation about safety windows and therapeutic dosing.

Claims 2–3: agonists vs antagonists are both covered

• Claim 2: TRPM8 agonist embodiment
• Claim 3: TRPM8 antagonist embodiment

This duality matters for competitive strategy because it expands the actionable universe to both directions of TRPM8 modulation, so a competitor cannot avoid infringement by simply switching pharmacology sign if they still bind TRPM8 specifically and produce tear secretion modulation.

Claims 4–6 and 9: disease-specific narrowing for xerophthalmia and epiphora

• Claim 4: xerophthalmia
• Claim 5: epiphora
• Claim 6: xerophthalmia associated with vitamin A deficit, Sjögren syndrome, rheumatologic diseases, burns
• Claim 9: epiphora associated with Graves-Basedow disease, corneal ulcers, Ackerman syndrome, allergies, bacterial conjunctivitis, blepharitis, facial nerve palsy, ectropion, nasolacrimal duct obstruction, lacrimal sac obstruction

Practical boundary impact

• The estate is not limited to “dry eye” in a narrow sense; it covers broader tear secretion problems including epiphora with specified etiologies.
• Validity and enforcement in practice will hinge on whether a given indication and therapeutic narrative can be mapped onto the listed disease categories.

Claims 10–14: chemotype constraint and enumerated “cooling” ligands

These dependent claims tie protection to a specific structural class and list candidate TRPM8 ligands:

• Claim 10: TRPM8 agonist comprises a 5-methyl-2-isopropyl cyclohexane core structure
• Claim 11: agonists include (non-exhaustive list in your claim text) WS-5, CPS-369, CPS-368, CPS-125, menthyl lactate, menthone glycerin acetal (Coolant Agent 10), (−)-Isopulegol, Cubelol, Hasegawa cooling compound, WS-11, WS-12, WS-30, WS-3, WS-14, IFF New GRASS cooling material, and combinations
• Claim 12: agonist is WS12
• Claim 13–14: antagonists likewise comprise the same 5-methyl-2-isopropyl cyclohexane core, with antagonists selected from MAD1d, MAD2e

Practical boundary impact

• If a competitor uses a TRPM8 ligand outside the recited 5-methyl-2-isopropyl cyclohexane core, claim 10/11/12/13/14 style narrowing may not read, but Claim 1 could still read if the molecule still “binds specifically to TRPM8” and modulates it to affect tear secretion.
• The enumerated ligands increase infringement leverage for product profiles aligned to known “cooling agent” chemotypes and WS-series compounds.

Claims 15–16: dosing frequency

• Claim 15: variable number of times per day
• Claim 16: 1 to 4 times a day

This supports enforcement against typical ophthalmic dosing regimens. A low-frequency regimen might be argued outside the dependent claim 16 but would still be potentially within claim 1 depending on how the claim is construed.

Claims 17–18: multi-ligand combinations

• Claim 17: at least two TRPM8 agonists
• Claim 18: at least two TRPM8 antagonists

This expands coverage to combination TRPM8 strategies, not only monotherapy.

Claims 19–25: combination therapy with standard ocular drug classes

• Claim 19: for xerophthalmia, composition includes TRPM8 binder + at least one additional xerophthalmia drug useful for treatment
• Claim 20: additional drug categories include corticoid, vitamin, muscarinic acetylcholine receptor agonist, immunosuppressant, or combinations
• Claim 21: vitamin = vitamin A
• Claim 22: muscarinic agonist = pylocarpine
• Claim 23: immunosuppressant = cyclosporine
• Claim 24–25: for epiphora, TRPM8 binder + additional drug useful for epiphora; at least one additional drug = antibiotic

Practical boundary impact

• This is a meaningful “commercial packaging” claim set. If a TRPM8 therapeutic is combined with cyclosporine or vitamin A or corticosteroid in an indication narrative matching xerophthalmia, the dependent claim structure creates multiple paths for infringement.
• For epiphora, the antibiotic combination dependency pushes enforceability toward infection/inflammation-driven epiphora treatment settings.

Claims 26–27: lubricant adjuncts

• Claim 26–27: composition further comprises a lubricant, enumerated as glycerol; hydroxypropyl methylcellulose; hydroxymethyl cellulose; carboxymethyl cellulose; polyethylene glycol; polyvinyl alcohol; hyaluronic acid; castor oil; mineral oil; hypromellose; carbomer; and combinations.

This aligns the patent with realistic ophthalmic formulation practice. A competitor using TRPM8 binder in a purely aqueous solution without lubricant may try to avoid the dependent claims 26–27, but claim 1 does not require lubricant.

Claims 28–30: subject and exclusions

• Claim 28: subject can be an animal subject (not limited to humans)
• Claim 29: TRPM8 binder is not menthol
• Claim 30: xerophthalmia symptoms include dryness sensation, ocular discomfort, or combination

Practical boundary impact

• Claim 29 is a carve-out. If a competitor uses menthol itself as the TRPM8 binder, dependent claim 29 may not apply, but claim 1 could still apply if menthol qualifies as a TRPM8-specific binder that modulates TRPM8 and changes tear secretion without cytotoxicity.
• The animal subject language may broaden enforcement pathways for veterinary ophthalmic products.

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Which TRPM8 agonists and antagonists are explicitly covered and where are the loopholes?

Short answer: The claim set explicitly covers WS12 as a TRPM8 agonist; agonists in the 5-methyl-2-isopropyl cyclohexane core class (WS-5, WS-11, WS-12, WS-14, WS-30, WS-3, CPS-125/368/369, cooling agents such as menthyl lactate, menthone glycerin acetal, (−)-isopulegol, Cubelol, and other named cooling compounds); and antagonists MAD1d and MAD2e in the same chemotype. The main “loophole” is using TRPM8 binders outside the specified chemotype and avoiding asserted dependent claim features like specified combinations, dosing range, lubricant classes, or menthol-specific embodiments.

Covered TRPM8 agonist universe by dependent claims (from your claim text)

• WS12 (explicit)
• WS-series: WS-5, WS-11, WS-12, WS-14, WS-30, WS-3
• CPS-series: CPS-369, CPS-368, CPS-125
• Cooling agents / monoterpene derivatives: menthyl lactate; menthone glycerin acetal (Coolant Agent 10); (−)-Isopulegol; Cubelol; Hasegawa’s cooling compound; IFF New GRASS cooling material; menthol
• Combinations of these

Covered TRPM8 antagonists (dependent claims)

• MAD1d, MAD2e, plus combinations

Design-around pressure points from the claims

1. Chemotype: If a product uses a TRPM8 ligand that is not within the 5-methyl-2-isopropyl cyclohexane core and is not one of the enumerated examples, it weakens dependent claim 10/11/12/13/14 without necessarily removing claim 1 exposure.
2. Menthol: Dependent claim 29 excludes menthol as the TRPM8 binder; it does not eliminate claim 1 exposure if menthol can still be argued as a TRPM8-specific binder with tear secretion modulation and no cytotoxicity.
3. Combination formulation: Avoiding the defined additional drug categories and antibiotic/lubricant classes may reduce dependent claim overlap but still leaves claim 1 as the broadest net.
4. Dose frequency: Dependent claim 16 is 1–4 times daily. A regimen outside that range may avoid claim 16 while remaining potentially within claim 1.

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How broad is infringement exposure: method claim 1 vs dependent claim stacking?

Short answer: Claim 1 is broad across ophthalmic tear disorders and across TRPM8 agonist/antagonist direction, so long as the administered molecule binds specifically to TRPM8, modulates TRPM8, changes tear secretion, and is non-cytotoxic. Dependent claims layer on additional constraints that may be used both for enforcement leverage and for narrowing constructions in invalidity or non-infringement.

Claim 1 elements that create factual and legal battlegrounds

• “Binding specifically to TRPM8”
• “Modulates the activity of the TRPM8 channel”
• “Increases or decreases tear secretion caused by the ophthalmic disease”
• “Not cytotoxic”

These can drive claim construction and evidence burdens. The strongest enforcement posture usually pairs pharmacology data with clinical tear secretion outcomes in the targeted ophthalmic indication.

Dependent claims as commercial leverage

Dependent claims match real-world product development choices:

• Indication mapping: xerophthalmia vs epiphora and listed subtypes
• Product composition: lubricant, vitamin A, cyclosporine, pylocarpine, corticoid, antibiotics
• Chemistry: WS-series, CPS-series, MAD antagonists

For a licensing or litigation strategy, those dependencies create multiple plausible “infringement hooks” depending on the competitor’s exact label and formulation.

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When does US 9,433,679 lose exclusivity and how does that affect generic entry risk?

No exclusivity timeline or expiration data is provided in the inputs you supplied. A precise expiration/exclusivity analysis requires the patent’s issuance details, priority dates, term adjustments, and any granted pediatric exclusivity and listed Orange Book/clinical exclusivity timelines for the associated FDA product. Without those, a quantified “when” would be incomplete.

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What is the Orange Book status of US 9,433,679 and which products are likely covered?

No Orange Book listings, associated drug (NDAs/ANDAs), or FDA regulatory product mapping is provided in the inputs you supplied. Without the associated FDA application number(s) and listed patents, coverage cannot be tied to specific marketed products.

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What patent litigation affects US 9,433,679 and how strong is the patent estate for TRPM8 ophthalmic methods?

No litigation docket entries, PTAB activity, reexamination records, or related-family patent portfolio data is provided in the inputs you supplied. A strength assessment that is actionable for litigation risk requires the broader family, prosecution history, claim amendments, and any invalidation/challenge outcomes.

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Which design-around routes are most credible under the claim language?

Short answer: Design-arounds should focus on separating from one or more Claim 1 “must-have” limitations (TRPM8-specific binding, TRPM8 modulation direction tied to tear secretion outcome, non-cytotoxic dosing) and from dependent claim features (agonist/antagonist class as used, chemotype, named ligands, disease subtype, combination drugs, antibiotics, lubricant list, and dosing frequency).

Route A: Use a non-TRPM8 target or non-specific binder

If the molecule does not “bind specifically to TRPM8” or does not modulate TRPM8 channel activity in the claimed manner, claim 1 should not read.

Route B: Avoid tear secretion outcome linkage in the indication narrative

Claim 1 requires increasing or decreasing tear secretion “caused by” the disease condition. A competitor can aim for an alternate therapeutic mechanism not framed as tear secretion modulation driven by TRPM8 binding.

Route C: Switch from WS/CPS/MAD chemotypes while retaining TRPM8 activity

Avoiding the 5-methyl-2-isopropyl cyclohexane core undermines dependent claims 10/11/12/13/14, but does not eliminate claim 1 risk if the new ligand still binds specifically to TRPM8 and changes tear secretion.

Route D: Avoid dependent add-ons: lubricant, vitamin A/cyclosporine/pylocarpine/corticoids/antibiotics

A formulation can try to avoid the enumerated lubricant classes and the defined combination drug categories. This reduces dependent claim exposure.

Route E: Dosing pattern outside the 1–4 times/day dependency

A dosing schedule outside the range may avoid dependent claim 16 while staying potentially within claim 1 exposure.

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Key Takeaways

• US 9,433,679 is a method-of-use TRPM8 ophthalmic patent centered on tear secretion modulation.
• Claim 1 is the broadest enforceable layer: TRPM8-specific binding, TRPM8 modulation, tear secretion increase or decrease, and non-cytotoxic dosing.
• Dependent claims create multiple enforcement paths by tying TRPM8 biology to specific indications (xerophthalmia vs epiphora and listed etiologies), specific chemotypes/ligands (including WS12 and MAD1d/MAD2e), and common ocular combo/formulation practices (vitamin A, cyclosporine, pylocarpine, corticoids, antibiotics, lubricants).
• Credible design-arounds most often target claim language fundamentals (specific TRPM8 binding/modulation, tear secretion outcome linkage, cytotoxicity) and secondarily avoid dependent claim features (chemotype and enumerated examples, lubricant/additive classes, and listed combination drug categories).

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FAQs

1. Can a TRPM8 antagonist be used for xerophthalmia under US 9,433,679?
   Yes, the claim set includes both agonists (Claim 2) and antagonists (Claim 3), and Claim 4 specifies xerophthalmia as a dependent disease embodiment.

2. Does the patent require menthol to be excluded?
   Claim 29 excludes menthol as the TRPM8-binding molecule in that dependent claim, but claim 1 is not limited by the menthol exclusion you provided.

3. What combinations increase risk of infringement for dry eye formulations?
   Xerophthalmia regimens that pair a TRPM8 binder with vitamin A, corticoids, pylocarpine, cyclosporine, or combinations fall within the dependent claim structure.

4. Is epiphora treatment covered only when antibiotics are co-administered?
   Claim 24 covers epiphora with TRPM8 binder plus at least one additional epiphora drug useful for treatment, and Claim 25 specifies antibiotic as an example of such additional drug.

5. If a competitor uses a different TRPM8 ligand not listed, are they still exposed?
   Yes, if the ligand still “binds specifically to TRPM8,” modulates TRPM8 channel activity, changes tear secretion, and is administered at a non-cytotoxic therapeutically effective amount, Claim 1 can still apply even if dependent chemotype/lists are avoided.

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References (APA)

1. United States Patent 9,433,679. (Claim text provided by user).

Drugs Protected by US Patent 9,433,679

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alcon Labs Inc	TRYPTYR	acoltremon	SOLUTION/DROPS;OPHTHALMIC	217370-001	May 28, 2025		RX	Yes	Yes	9,433,679					TREATMENT OF THE SIGNS AND SYMPTOMS OF DRY EYE DISEASE (DED)

International Family Members for US Patent 9,433,679

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2614860
European Patent Office	4268814
Spain	2377785
Japan	2013537887
Japan	2017036298
Japan	2019131621
Japan	2021107422