Details for Patent: 7,476,689

Summary for Patent: 7,476,689

Title:	Therapeutic compositions for intranasal administration which include KETOROLAC
Abstract:	An analgesic/anti-inflammatory pharmaceutical dosage form which comprises an effective amount of an active ingredient selected from the group consisting of racemic 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, optically active forms thereof and pharmaceutically acceptable salts thereof, in combination with a pharmaceutically acceptable excipient or diluent, said dosage form being an intranasally administrable dosage form.
Inventor(s):	Giancarlo Santus, Giuseppe Bottoni, Ettore Bilato
Assignee:	Recordati Ireland Ltd , Zyla Life Sciences US Inc
Application Number:	US10/792,457
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Scope and Claims Analysis for US Patent 7,476,689 (Intranasal Aqueous Analgesic of 5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic Acid): What It Covers, Where It Is Narrow, and What Can Still Launch Around

US Patent 7,476,689 claims an intranasally administered aqueous analgesic containing 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid (racemic, optically active, and/or pharmaceutically acceptable salts), with specific concentration, dose range, systemic exposure window, and formulation/excipient attributes. The independent claim (claim 1) is drafted as a tight combination of: (i) drug identity/form, (ii) solution strength (5–20% w/v), (iii) intranasal spraying into the nasal cavity, and (iv) a pharmacokinetic performance requirement tying administration to plasma levels of 0.3–5 mg/L. Dependent claims then narrow to mg-per-dose, single-dose, a 15% w/v embodiment, and specific excipient classes (bioadhesive, viscosity-switch polymer, and absorption promoters such as polyoxyethylene (9) lauryl alcohol, sodium glycocholate, lysophosphatidyl choline), plus a device article claim covering an atomizer.

The practical upshot is that infringement risk centers on whether a competitor’s intranasal aqueous analgesic both (a) falls within the concentration and dose ranges and (b) achieves the systemic plasma exposure window. That plasma-range limitation is a meaningful choke point if it is construed as a structural/functional product limitation tied to how the dosage form performs in humans, not merely a target formulation.

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What does US Patent 7,476,689 claim for intranasal aqueous analgesics?

Featured snippet answer: Claim 1 covers an intranasal aqueous solution for systemic pain treatment with 5–20% w/v of 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid (racemic/optical/salts) that, when given intranasally at 0.5–40 mg, generates 0.3–5 mg/L plasma.

Claim 1: Core scope elements (a claim chart)

Claim 1 is the anchor. Every competitor analysis starts by mapping each limitation:

1. Analgesic pharmaceutical aqueous dosage form
2. Active ingredient is selected from:
   • racemic 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid
   • optically active forms
   • pharmaceutically acceptable salts
3. Solution containing 5–20% (w/v) active ingredient
4. Intranasal administration by spraying into the nasal cavity
5. Systemic pain treatment by intranasal route
6. Human dosing parameter: intranasal at 0.5–40 mg
7. Pharmacokinetic constraint: generates plasma levels within 0.3–5 mg/L

Why the plasma limitation matters

A limitation of the form “generates plasma levels within range X” can be treated as:

• a performance limitation (product-by-process or functional performance), and/or
• a characteristic of the claimed composition when administered as specified.

Under that construction, a competitor could attempt to avoid infringement by:

• using a different intranasal formulation that consistently produces plasma levels outside 0.3–5 mg/L (below 0.3 or above 5), or
• altering bioavailability so the achieved systemic exposure fails the recited range even if concentration and route match.

If the court treats the plasma range as inherently met once the structural formulation is practiced, the “workaround by exposure” becomes harder to defend. The claim text is drafted tightly enough that enforcement may argue inherent attainment when the specified 5–20% w/v solution is administered at 0.5–40 mg intranasally. Still, the range provides a technical litigation lever because plasma outcomes can be measured.

Claims 2, 4, 3: Dose quantity and form-factor narrowing

• Claim 2: dosage form of claim 1 comprising 5–30 mg active ingredient
• Claim 3: claim 1 in a single-dose form
• Claim 4: claim 1 containing 15% (w/v) active ingredient (a specific formulation strength)

These create sub-ranges that reduce the field of equivalent infringement:

• A competitor staying at <5 mg per dose or >30 mg may fall outside dependent claim 2 (but not necessarily claim 1 if still within claim 1’s 0.5–40 mg dosing range).
• A competitor using multi-dose devices could still infringe claim 1 but avoid claim 3’s “single-dose form” limitation.

Claims 5–8: Bioadhesion, viscosity switch, and absorption promoters

• Claim 5: excipient comprises a bioadhesive
• Claim 6: polymer provides lower viscosity at room temperature, then increases viscosity at body temperature
• Claim 7: further excipient includes an intranasal absorption promoter
• Claim 8: promoter selected from:
  • polyoxyethylene (9) lauryl alcohol
  • sodium glycocholate
  • lysophosphatidyl choline

These dependent claims are not alternatives to claim 1; they are extra limitations that only matter if the base elements are met. But they are also a guide to the most enforcement-friendly embodiments: if a generic or reformulation uses absorption promoters or viscosity-switch polymers, risk increases.

Claim 9–12: Method-of-treatment claim with same pharmacokinetic anchor

• Claim 9: method for treating pain in a patient by spraying intranasally an aqueous composition containing 0.5–40 mg systemic amount, with 5–20% w/v solution strength, and sufficient to achieve plasma 0.3–5 mg/L
• Claim 10: effective amount within 5–30 mg
• Claim 11: composition is a 15% w/v solution
• Claim 12: patient is human

The method claim is drafted to align tightly with claim 1. A competitor’s product-for-sale can infringe claim 9 if it is used as intended and meets the exposure criteria.

Claims 13–22: Article of manufacture (atomizer + instructions)

• Claim 13: article of manufacture: atomizer containing an aqueous analgesic composition with 0.5–40 mg per dose, concentration 5–20% w/v, intranasally administrable for systemic pain
• Claims 14–20: mirror dose/concentration/excipient limitations:
  • 5–30 mg per dose (claim 14)
  • single-dose form (claim 15)
  • 15% w/v (claim 16)
  • bioadhesive (claim 17)
  • viscosity-switch polymer (claim 18)
  • absorption promoter (claim 19), and specific promoters listed in claim 20
• Claim 21: article includes written instructions for intranasal treatment
• Claim 22: “dosage form of claim 1 in the form of a spray”

The article-of-manufacture claim is strategically important for enforcement against the combination of product + device. It captures not just the formulation but the atomizer-delivered intranasal spray.

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How narrow is the claim set: where are the strongest constraints and the easiest launch-avoidance points?

Featured snippet answer: The strongest constraints are the combination of 5–20% w/v solution strength, intranasal spraying, dose 0.5–40 mg, and achieving 0.3–5 mg/L plasma; the easiest avoidance levers are changing concentration and dose outside ranges, shifting systemic exposure outside the plasma window, and avoiding the specific excipient classes only if those are treated as required.

Constraints in claim 1 that are hardest to change without changing product identity

1. Drug identity and form
   Covers racemic, optically active forms, and salts. A “skip” strategy using a different stereoisomer alone does not avoid the claim by text, because claim 1 explicitly includes optically active forms.

2. Aqueous solution strength (5–20% w/v)
   This is a clear numeric limit. If a competitor uses a lower concentration (for example 2–4% w/v) or a higher one (>20% w/v), claim 1 is less likely to be met, even if the total mg per actuation is tuned.

3. Intranasal spraying
   A formulation that is delivered intranasally but not by “spraying into a nasal cavity” could be argued to fall outside, depending on construction. Typical nasal sprays and atomizers will likely be considered “spraying.”

4. Plasma exposure window (0.3–5 mg/L)
   This is the most litigation-relevant “functionally defined” limitation. If a competitor’s formulation produces plasma levels below 0.3 or above 5 consistently at the claimed dosing, it may avoid the claim.

Points of relative flexibility for competitors

• Bioadhesive / absorption promoters / viscosity-switch polymers
  These appear only in dependent claims. A competitor could avoid using those excipients and still risk claim 1 (because claim 1 does not require them), but would reduce risk under the dependent claims.

• Single-dose packaging / “atomizer” configuration
  Multi-dose devices might help avoid claim 3 or device article claim depending on how the competitor markets and how the device is built. But claim 1 (a dosage form) and claim 9 (method) remain the broader targets.

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What formulations and excipients are explicitly protected by US 7,476,689?

Featured snippet answer: The patent protects intranasal aqueous solutions at 5–20% w/v delivering 0.5–40 mg systemically to reach plasma 0.3–5 mg/L, and dependent claims add protection for formulations using bioadhesives, temperature-triggered viscosity-switch polymers, and intranasal absorption promoters including polyoxyethylene (9) lauryl alcohol, sodium glycocholate, and lysophosphatidyl choline.

Dependent excipient claims (claims 5–8, 17–20)

• Bioadhesive excipient
  Claim 5/17: any excipient characterized as bioadhesive.

• Viscosity-switch polymer (room temperature low, body temperature higher)
  Claim 6/18: polymer that thickens upon warming. This suggests a platform approach (thermoresponsive polymers), but the claim language is functionally framed.

• Absorption promoters
  Claim 7/19: includes a promoter
  Claim 8/20: specific exemplars

Enforcement profile

If a generic or reformulation uses one of the listed promoters, and the composition also hits the base claim numeric and plasma windows, it is closer to the center of the patent.

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What method-of-use and patient population limitations exist?

Featured snippet answer: Claim 9 is a pain-treatment method in humans via intranasal spraying of an aqueous solution meeting the same concentration, dose, and plasma exposure constraints.

• Patient: human (claim 12)
• Route: intranasal spraying (claim 9)
• PK performance: plasma 0.3–5 mg/L (claim 9)

This structure supports two enforcement theories:

1. Product use infringement: the act of treating pain intranasally with the formulation meeting claim 1 triggers claim 9.
2. Article enforcement: the packaging with instructions (claim 21) supports inducement or direct infringement theories in jurisdictions recognizing instruction-based infringement of product articles.

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What is an “article of manufacture” claim here and why does it matter for generic entry?

Featured snippet answer: Claim 13 covers an atomizer loaded with the specified intranasal aqueous analgesic composition, with mg-per-dose and concentration limits matching claim 1.

How claim 13 changes the infringement landscape

A product can be designed to reduce formulation-based risk, but the atomizer and instructions can still keep the case in the patent’s orbit. For generic entrants, the key is whether their drug-device combination:

• uses an atomizer delivering the specified mg-per-dose (0.5–40 mg),
• delivers a 5–20% w/v solution, and
• is marketed and used for systemic pain via intranasal spraying.

If the generic uses a different delivery device (for example, a different spray mechanism that is not “spraying” in claim construction terms), claim 22 and claim 13 are potential target areas. If the generic uses the same drug and formulation but a different device, risk shifts toward claims 1 and 9.

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What launch-around strategies exist based solely on the claim language?

Featured snippet answer: The claim language suggests three principal launch-around levers: (i) move outside 5–20% w/v concentration, (ii) move outside 0.5–40 mg dosing or dependent 5–30 mg, and (iii) ensure plasma exposure at clinically relevant intranasal doses is outside 0.3–5 mg/L.

Concentration and dose levers

• Avoid 5–20% w/v by using a different concentration regime.
• Avoid 0.5–40 mg per administration, or avoid 5–30 mg if focusing on dependent claim 2/10.

Exposure lever (PK non-infringement)

If a competitor can design a formulation that is still intranasal aqueous but reliably produces plasma levels outside 0.3–5 mg/L, that may defeat claim 1/9, even if concentration and dose match, depending on claim construction.

Excipient lever (dependent claims)

If using no bioadhesive, no viscosity-switch thickening polymer, and no specified absorption promoters, the competitor may still infringe claim 1/9 but can narrow exposure by moving away from dependent claim embodiments.

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How strong is the patent estate for this technology stack (from the claims provided)?

Featured snippet answer: As drafted, the estate is strong against close variants because it combines drug identity with numeric concentration, route, dose, and a human plasma exposure window, while also covering a device article.

Strength features

• Tight numeric constraints: 5–20% w/v, 0.5–40 mg, 0.3–5 mg/L
• Covers multiple drug forms: racemic, optically active, salts
• Includes both composition and method claims
• Includes device/atomizer and instructions, supporting enforcement beyond “formulation-only” designs

Weakness features (claim-level)

• Only claims explicitly disclosed here define intranasal delivery of the same drug. If a competitor uses a different analgesic active ingredient, the patent does not apply by text.
• Dependent claims are not required for claim 1/9; a competitor can remove listed excipient features and still risk independent claim infringement.

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How to evaluate freedom-to-operate for an intranasal generic or reformulated product

Featured snippet answer: For FTO, treat claim 1 and claim 9 as the gatekeepers. Confirm whether your proposed intranasal aqueous product:

• contains 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid (racemic/optical/salt),
• is a 5–20% w/v solution,
• is delivered as intranasal spray into the nasal cavity,
• is dosed intranasally at 0.5–40 mg per administration, and
• produces systemic plasma levels 0.3–5 mg/L in humans.

Practical claim-mapping checklist

• Composition: concentration (w/v), aqueous solution, active identity and salt form
• Administration: spraying into nasal cavity, atomizer type, single-dose vs multi-dose
• PK: measured plasma levels in the claimed dose regimen
• Excipients: whether bioadhesives, viscosity-switch polymers, or listed promoters are used (relevant to dependent claims)

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What patent landscape and timing issues exist for US 7,476,689?

No landscape can be constructed from the claim text alone because the key inputs are missing: the publication history, priority dates, prosecution record, full patent family membership, and FDA product linkage. Without those, it is impossible to provide reliable expiration dates, exclusivity calendars, Orange Book status, or the presence/absence of related method-of-use or formulation patents in the same family.

Because the claim language and patent number are not sufficient to determine regulatory status or family scope, no timeline, expiration, or litigation/Paragraph IV risk can be stated accurately.

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Key Takeaways

• US 7,476,689 is primarily an intranasal aqueous formulation patent with a narrow technical perimeter: 5–20% w/v solution strength, 0.5–40 mg intranasal dosing, and 0.3–5 mg/L human plasma exposure.
• The patent adds protection for dose strength embodiments (including 5–30 mg and 15% w/v) and product form (including single-dose).
• Dependent claims broaden enforcement leverage through excipient-specific limitations: bioadhesives, temperature-triggered viscosity-switch polymers, and absorption promoters including polyoxyethylene (9) lauryl alcohol, sodium glycocholate, and lysophosphatidyl choline.
• The patent includes both method-of-treatment and article-of-manufacture (atomizer + instructions) claims, which can increase infringement theories in generic entry scenarios.
• Claim-avoidance strategies suggested by the text are to shift outside the concentration, dose, and especially the plasma exposure window.

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FAQs

1. Does US 7,476,689 cover both racemic and optically active forms of the active ingredient?
   Yes. Claim 1 explicitly includes racemic, optically active forms, and pharmaceutically acceptable salts.

2. Is intranasal delivery required to be by a spray/atomizer under US 7,476,689?
   Yes for the core independent claims because delivery is defined as “spraying into a nasal cavity,” and the article claim expressly recites an atomizer.

3. Do bioadhesives and viscosity-switch polymers have to be present to infringe?
   No. They appear in dependent claims (claims 5–8), while claim 1 only requires the base aqueous solution and the PK/systemic plasma range.

4. What parameter most directly differentiates infringement from a near-miss intranasal formulation?
   The human plasma exposure limitation of 0.3–5 mg/L at the claimed intranasal dose regimen.

5. Can a competitor avoid the dependent excipient claims by using different promoters?
   It can reduce risk under the dependent claims, but it does not avoid the independent claim if the formulation still meets claim 1’s concentration, route, dose, and plasma-range requirements.

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References

No sources were cited because only the claim text provided by the user was used, and no publication/Orange Book/regulatory/patent-family data were reliably provided.

Drugs Protected by US Patent 7,476,689

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 7,476,689

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Italy	MI91A2024	Jul 22, 1991

International Family Members for US Patent 7,476,689

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	130758
Germany	69206345
Denmark	0524587
European Patent Office	0524587
Spain	2082288