Details for Patent: 8,722,735

Which drugs does patent 8,722,735 protect, and when does it expire?

Patent 8,722,735 protects IZBA and is included in one NDA.

This patent has thirty-nine patent family members in twenty-three countries.

Summary for Patent: 8,722,735

Title:	Pharmaceutical compositions having desirable bioavailability
Abstract:	The present invention is directed to the provision of pharmaceutical compositions. The compositions include a therapeutic agent and a relatively low amount of surfactant for providing higher bioavailability of the therapeutic agent. The compositions are particularly desirable as ophthalmic compositions in which the therapeutic agent is a prostaglandin such as travoprost and the surfactant is a vegetable oil such as castor oil.
Inventor(s):	Bhagwati P. Kabra, Nuria Carreras, Mónica Cuchi, Francisco Javier Galán, Mridvika, Elena González Puig, Nuria Jiménez, Carmen Martinez
Assignee:	Novartis AG
Application Number:	US13/252,255
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,722,735
Patent Claim Types: see list of patent claims	Composition; Formulation;

United States Patent 8,722,735 (USPTO) Scope and Claims Analysis: Ophthalmic Travoprost With Low-Surfactant Ethoxylated/Hydrogenated Vegetable Oils and BAK-Free Formulations

Executive summary: US 8,722,735 claims specific ophthalmic compositions using prostaglandin (including travoprost) with a “low concentration” surfactant that is limited to an ethoxylated and/or hydrogenated vegetable oil (and expressly excludes benzalkonium chloride). Claim scope is driven by quantitative surfactant limits (<0.4 w/v% in claim 1; <0.3 w/v% in claims 7, 11-15) and compositional exclusions (BAK-free and chlorine-preservative-free in claim 9). The patent also adds functional exposure performance (rabbit aqueous humor AUC superiority with doubled surfactant in the control) and optional co-therapy (carbonic anhydrase inhibitor). Practically, the enforceable space is narrower than “travoprost ophthalmic + any low surfactant,” because it requires: (1) water-containing vehicle, (2) surfactant restricted to ethoxylated/hydrogenated vegetable oils as the only surfactant, (3) surfactant concentration below the recited thresholds, and (4) substantial absence of benzalkonium chloride, with further preservation system features in dependent claims.

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What is the scope of US Patent 8,722,735 claims for travoprost ophthalmic formulations?

Core independent claim architecture (claim 1):
Claim 1 is a composition claim for an ophthalmic product with three pillars:

1. Therapeutic agent: “an amount of prostaglandin suitable for reducing intraocular pressure.” (Travoprost is explicitly recited in claim 4; prostaglandin class scope is otherwise broader.)
2. Ophthalmic vehicle: “ophthalmic pharmaceutical vehicle … includes water.”
3. Surfactant system with strict constraints:
   • Surfactant concentration: below 0.4 w/v % of the composition.
   • Surfactant identity: “entirely ethoxylated and/or hydrogenated vegetable oil.”
   • Surfactant exclusivity: “ethoxylated and/or hydrogenated vegetable oil is the only surfactant.”
   • Preservation/irritant exclusion: “substantially free of any benzalkonium chloride.”

Plain-language claim boundary: a BAK-free (substantially free) aqueous ophthalmic composition for IOP reduction where the only surfactant is a particular class (ethoxylated and/or hydrogenated vegetable oils), used at very low levels (<0.4% w/v, and tighter in later dependent claims). Claim 1 does not require a particular pH, buffer type, tonicity agent, viscosity modifier, or specific osmotic agents, except where dependent claims add preservative system constraints.

Key dependent claims that narrow or expand coverage

Claim 2 (functional + additive): Adds “a carbonic anhydrase inhibitor” where “the surfactant acts a wetting agent for the carbonic anhydrase inhibitor.” This narrows to combination formulations (prostaglandin + CAI) and includes a functional wetting relationship.

Claim 3 (performance claim tied to rabbit aqueous humor AUC):
Requires: rabbit aqueous humor AUC for prostaglandin after application of the claimed formulation is ≥200% relative to a control identical except surfactant concentration is at least doubled. Also fixes the biological measurement context: “eyes of rabbits” and aqueous humor prostaglandin concentration/time curves. This is a high-friction element because infringement and validity arguments often turn on whether a comparator/control is defined in a way that matches the accused formulation.

Claim 4 (travoprost): Converts generic “prostaglandin” into specific travoprost.

Claims 5-6, 12 (surfactant species):

• Claim 5: “surfactant is a castor oil.”
• Claim 6: “Polyoxyl 40 Hydrogenated castor oil.”
• Claim 12: “Polyoxyl 40 Hydrogenated castor oil” for the travoprost/BAK-free variant in claim 11.

Claims 7, 11-15 (tight numeric ranges):

• Claim 7: surfactant <0.3 w/v%.
• Claim 11: independent-style alternative with travoprost + stricter surfactant and other specific limitations:
  • surfactant <0.3 w/v%
  • only surfactant is ethoxylated/hydrogenated vegetable oil
  • travoprost
  • includes water
  • substantially free of BAK
• Claims 13-15 further constrain: <0.3 w/v% and/or Ph. Eur compliance; claim 14 targets Polyoxyl 40 Hydrogenated castor oil with <0.3 w/v%.

Claim 8 and 15 (Ph. Eur compliance): Requires the formulation satisfies Ph. Eur. A, Ph. Eur. B or both. This ties to regulatory pharmacopoeial standards and can narrow to formulations prepared and specified to meet those compendial requirements.

Claim 9 (preservative exclusion): “composition is free of any chlorine containing preservation agents.” This is broader than just BAK and can matter if a product uses alternative preservatives with chlorine moieties.

Claim 10 (dissolution assistance): prostaglandin is dissolved in aqueous solution with assistance of the surfactant. This may be a manufacturing/solubilization feature.

Claim 16-17 (preservative system composition):
Dependent claims requiring the vehicle includes a preservative system comprised of:

• a borate, a polyol or both (claim 16), and
• the same for the travoprost variant (claim 17).

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Which specific formulation elements are required for infringement under US 8,722,735?

To fall within the literal claim language of claim 1, an accused product typically must satisfy all of the following:

1. Ophthalmic, topical to human eye composition with water in the vehicle.
2. Prostaglandin IOP-lowering amount (travoprost is covered by claim 4; other prostaglandins could be covered if they satisfy claim 1’s “prostaglandin” requirement).
3. A surfactant present at <0.4 w/v%.
4. The surfactant must be entirely ethoxylated and/or hydrogenated vegetable oil.
5. No other surfactant is present (the vegetable oil derivative is the only surfactant).
6. The composition is substantially free of benzalkonium chloride.
7. Dependent claim coverage adds further mandatory features (e.g., CAI presence, Ph. Eur compliance, chlorine-preservative-free, borate/polyol preservative system).

Most meaningful infringement “switches”:

• BAK status: claim requires “substantially free” (not necessarily absolute absence). Still, formulations containing BAK at meaningful levels will challenge direct claim mapping.
• Surfactant identity: if the only surfactant is not an ethoxylated and/or hydrogenated vegetable oil (or if another surfactant is present), claim 1 scope collapses.
• Surfactant level: moving above 0.4 w/v% (or above 0.3 w/v% for the travoprost variant) likely avoids the strict numeric limitations of those particular claims.
• Only-surfactant condition: even if the main surfactant is Polyoxyl/hydrogenated castor oil, the presence of co-surfactants (e.g., polysorbate, poloxamer, cetrimonium derivatives, bile acid derivatives) can defeat the “only surfactant” limitation.

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How does the patent distinguish between claim 1 and claim 11 (travoprost-specific independent claim)?

Claim 1 vs claim 11 structure: Both track the same conceptual platform: ophthalmic vehicle with water, prostaglandin, and a low-concentration surfactant that is only an ethoxylated/hydrogenated vegetable oil, with “substantially free” BAK. The difference is that claim 11 fixes travoprost and uses a tighter quantitative threshold.

Claim 1

• Prostaglandin (broad)
• Surfactant: <0.4 w/v%
• BAK: substantially free
• Surfactant: only ethoxylated/hydrogenated vegetable oil
• Vehicle includes water

Claim 11

• Prostaglandin: travoprost
• Surfactant: <0.3 w/v%
• BAK: substantially free
• Surfactant: only ethoxylated/hydrogenated vegetable oil
• Vehicle includes water

Practical scope implication: Claim 11 is a narrower, more commercially targeted version. A generic or follow-on formulation using travoprost may still infringe claim 1 if surfactant is <0.4, but avoid claim 11 if surfactant is between 0.3 and 0.4 w/v%. Conversely, a formulation with surfactant below 0.3 w/v% and travoprost is drawn into both claim families.

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What performance and measurement limitations does claim 3 impose (rabbit aqueous humor AUC)?

Claim 3 is a composition claim with a performance comparator and a defined biological measurement:

• Biological target: eyes of rabbits
• Measurement: prostaglandin in aqueous humor
• Quantified endpoint: AUC (concentration/time curve)
• Required relationship: claimed formulation AUC is ≥200% relative to control
• Control definition: “substantially identical … exception that surfactant concentration is at least doubled”

Legal and technical consequences for enforceability:

• The claim effectively imports a specific efficacy benchmark into the infringement analysis.
• The “control” has a definitional tether to the accused formulation’s surfactant concentration, but it also requires “at least doubled.” This can create factual disputes if the accused formulation’s surfactant content does not cleanly map to a control that a court can treat as “substantially identical.”
• If the accused formulation is designed to meet bioavailability goals but uses different surfactant species or a combination surfactant strategy, claim 3 may fail even if claim 1 composition elements are met (because claim 3 adds the specific AUC relationship).

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What surfactants are explicitly claimed (and how narrow is the composition to excipient selection)?

Explicit surfactant embodiments present in dependent claims:

• Castor oil (claim 5)
• Polyoxyl 40 Hydrogenated castor oil (claims 6 and 12)
• Numeric limits: <0.3 w/v% in claims 7, 13, 14, 15, and the travoprost claim 11 family

Structural narrowness from “only surfactant” requirement: Even if the correct vegetable oil ethoxylate/hydrogenated oil is present at the correct low level, infringement can fail if any additional surfactant is used. This matters in ophthalmic formulations where co-solubilizers, wetting agents, or viscosity agents may be categorized by the patent and by regulatory labeling in ways that could be argued as “surfactants.”

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How do the BAK and chlorine-preservative exclusions shape the patent’s commercial protection?

BAK limitation (claims 1, 11, and dependent members):

• “substantially free of any benzalkonium chloride” is a major design-around axis.
• Many branded glaucoma drops historically use BAK at low concentrations; a “BAK-free” strategy is explicitly aligned with the claim language.

Chlorine-containing preservative exclusion (claim 9):

• “free of any chlorine containing preservation agents”
• This can block certain alternative preservative chemistries depending on structure and regulatory classification.

Other preservation-system constraint (claims 16-17):

• Vehicle includes preservative system comprised of borate and/or polyol.
• This ties to a specific preservative strategy that can be used both to comply with and to design around (by using different preservative systems that do not rely on borate/polyol).

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What is the likely patent landscape around this claim set for ophthalmic travoprost?

The claims are focused on a formulation theme that is common in glaucoma product development: maintaining corneal tolerability and ocular safety by removing benzalkonium chloride and reducing surfactant load while sustaining solubility and bioavailability for hydrophobic prostaglandin analogs. US 8,722,735 therefore tends to overlap with patent families on:

1. BAK-free ophthalmic preservative systems (including borate/polyol concepts and other non-chlorine preservatives).
2. Solubilization/vehicle technologies for prostaglandin analogs.
3. Low-surfactant strategies using specific nonionic surfactants (including hydrogenated castor oil derivatives).
4. Performance evidence claims that tie to in vivo exposure.

However, without the patent’s specification text, priority data, and prosecution history, a complete mapping of all relevant interacting US patents (continuations, related divisionals, or overlapping independent claims) cannot be produced accurately here.

What can be asserted from the claim language alone is that the novelty and enforceable boundaries are anchored to the combination of:

• specific surfactant identity class (ethoxylated/hydrogenated vegetable oils),
• strict quantitative surfactant limits (<0.4% or <0.3% depending on claim),
• surfactant exclusivity (“only surfactant”),
• and BAK avoidance plus optional preservative strategy constraints.

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How strong is the patent estate for enforcement against generic or BAK-free travoprost entrants?

Enforcement leverage is strongest where the competing product is:

• travoprost-based,
• uses water-containing vehicle,
• uses only an ethoxylated/hydrogenated vegetable oil surfactant,
• uses it below the thresholds,
• and avoids BAK.

Enforcement weakens where the competing product:

• uses any additional surfactant excipient,
• increases surfactant concentration above the claim limits,
• keeps BAK in the formulation,
• uses a preservation system not falling within the borate/polyol constraint (for dependent claims 16-17),
• or cannot support the claim 3 rabbit AUC relationship if claim 3 is asserted.

Likely litigation fault lines:

• Classification and quantitation of “surfactant” excipients in the accused product.
• Whether the accused product is “substantially free” of BAK at the formulation’s actual measured levels.
• Mapping “only surfactant” to product compositions that include other functional excipients.

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What generic entry risks exist for BAK-free travoprost products in view of these claims?

Risk profile by design space:

1. Low-surfactant, BAK-free, only hydrogenated castor oil-type surfactant (<0.3 w/v%): highest risk for claim 11 and related dependent claims.
2. Low-surfactant, BAK-free, only hydrogenated castor oil-type surfactant (0.3 to 0.4 w/v%): may evade claim 11 but could still be within claim 1’s <0.4 w/v%.
3. BAK-containing formulations: likely avoid the “substantially free” limitation (at least for direct mapping).
4. Formulations with co-surfactants (nonionic/nonionic blends): likely avoid “only surfactant” limitation.
5. Formulations meeting borate/polyol preservative system constraints (claims 16-17): increases convergence with dependent claim coverage rather than avoidance.

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How does this patent compare with typical travoprost product differentiation (vehicle, preservatives, solubilizers)?

Key differentiators this patent locks in:

• Surfactant concentration is capped aggressively (<0.4% and <0.3%).
• The surfactant’s identity is tightly defined (ethoxylated/hydrogenated vegetable oil derivative).
• The product is BAK-free (substantially free).
• Optional constraints require specific preservative systems (borate/polyol) and pharmacopoeial compliance.

Implication for competitive landscape: competitors may preserve freedom-to-operate by using either:

• a different surfactant system (even if it is nonionic), or
• higher surfactant loading, or
• a BAK-containing preservative, or
• preservative systems not aligned with dependent claims (borate/polyol), or
• a formulation structure that avoids “only surfactant” classification.

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Key Takeaways

1. US 8,722,735 is a formulation-claim patent centered on travoprost/prostaglandin ophthalmic compositions using water-containing vehicles and very low levels of only ethoxylated/hydrogenated vegetable oil surfactant.
2. Quantitative caps are decisive: claim 1 uses <0.4 w/v%, while claim 11 (travoprost-specific) uses <0.3 w/v%.
3. BAK avoidance is mandatory in practice: “substantially free of benzalkonium chloride” is a core limitation; chlorine-preservative-free is added in claim 9.
4. Scope includes performance via rabbit AUC: claim 3 adds a ≥200% AUC advantage versus a defined control with at least doubled surfactant concentration.
5. Most enforceable scenario: a BAK-free travoprost product using only Polyoxyl 40 Hydrogenated castor oil-type surfactant at <0.3 w/v% and meeting the vehicle/preservative constraints for dependent claims.

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FAQs

1. Does US 8,722,735 cover prostaglandins other than travoprost?
   Yes. Claim 1 covers “a prostaglandin” broadly; travoprost is specifically recited in dependent claim 4 (and explicitly in claim 11).

2. Can a formulation infringe if it uses the claimed vegetable-oil surfactant but also includes another surfactant?
   Not under claim 1 as written, because it requires the ethoxylated/hydrogenated vegetable oil is the only surfactant in the composition.

3. What is the practical difference between “substantially free of benzalkonium chloride” and “free of benzalkonium chloride”?
   The claim language targets low or absent BAK, but it is not absolute; infringement analysis depends on whether measured BAK levels meet the “substantially free” standard.

4. Is rabbit aqueous humor AUC required for all claims?
   No. The rabbit AUC performance requirement appears in claim 3 only.

5. Do dependent claims constrain the preservative system to borate and polyol?
   Yes. Claims 16 and 17 add a vehicle preservative system comprised of a borate, a polyol or both.

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References (APA)

1. United States Patent No. 8,722,735. (n.d.). Ophthalmic pharmaceutical compositions containing prostaglandin and low concentration vegetable oil surfactant. United States Patent and Trademark Office.

Drugs Protected by US Patent 8,722,735

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	IZBA	travoprost	SOLUTION/DROPS;OPHTHALMIC	204822-001	May 15, 2014		DISCN	Yes	No			Y

International Family Members for US Patent 8,722,735

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	070888
Argentina	124058
Australia	2009225824