Details for Patent: 5,733,569

Summary for Patent: 5,733,569

Title:	Galenic compositions comprising calcitonin and their use
Abstract:	Pharmaceutical compositions for nasal administration comprising i) a calcitonin, and ii) benzalkonium chloride, and/or iv) a surfactant, suitable for application to the nasal mucosa, in iii) a liquid diluent or carrier, suitable for application to the nasal mucosa. The compositions are suitably adapted for administration in the form of a nasal spray.
Inventor(s):	Moise Azria, Thomas Cavanak
Assignee:	SEBELA INTERNATIONAL 2 Ltd
Application Number:	US08/471,118
Patent Claim Types: see list of patent claims	Use; Composition; Device;

US Patent 5,733,569 Scope and Claims Analysis: Calcitonin + Benzalkonium Chloride Liquid Nasal Spray Patent Landscape (US)

US Patent 5,733,569 claims a narrow but multi-layered combination technology: a liquid nasal spray containing calcitonin (specific subtypes enumerated), formulated with benzalkonium chloride (BAK) to enhance nasal bioavailability, delivered in an aqueous nasal carrier, with multiple dependent claim constraints on pH, osmotic pressure, viscosity, dose concentration (MRC units/mL), and optional surfactants. The patent also extends scope to an applicator device containing the formulation and to a method of administering the calcitonin nasal composition.

Because the claims are composition- and parameter-defined, the practical freedom-to-operate hinges on whether an accused product uses:

1. any of the enumerated calcitonins/salts,
2. BAK at a formulation- and/or device-contained level, and
3. aqueous nasal carrier plus the claimed physicochemical windows (depending on which claim(s) are asserted).

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What exactly does US 5,733,569 claim for a calcitonin nasal spray?

Independent claim 1: core composition

Claim 1 is the technical center of gravity. It is written as a liquid pharmaceutical composition suitable for administration as a liquid nasal spray, comprising:

• Calcitonin (or a pharmaceutically acceptable acid addition salt) where calcitonin is limited to:
  • salmon calcitonin
  • human calcitonin
  • porcine calcitonin
  • 1.7-Asu-eel calcitonin
• Therapeutically effective amount of calcitonin
• Effective amount of benzalkonium chloride to enhance bioavailability when administered to nasal mucosa
• A pharmaceutically acceptable, aqueous liquid nasal carrier

This claim is broad on the presence of BAK and an aqueous nasal carrier, and narrow on calcitonin species (enumerated list).

Claim 7: device/applicator extension

Claim 7 converts the composition into a nasal applicator device claim:

• Device containing the formulation
• Formulation must include calcitonin (same enumerated list) and BAK and aqueous carrier

Claim 8 further limits device type to “a nasal aerosol applicator.”

Claim 9: method-of-administration

Claim 9 claims administration to a subject by the nasal route using the claimed composition containing the same calcitonin list, BAK, and aqueous carrier.

Net effect:

• Composition (claim 1)
• Device with composition (claims 7-8)
• Method (claim 9)

This matters for enforcement because some generic/“follow-on” entrants may attempt to avoid composition-level overlap by changing device or labeling, but claim sets cover both.

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How broad are the dependent claims on formulation parameters (pH, osmotic pressure, viscosity, surfactants)?

pH windows: claims 2-4 and 20-25

• Claim 2: pH about 3 to about 5
• Claim 3: pH about 3.5 to 4.5
• Claim 4: pH achieved using hydrochloric acid
• Claim 20: applicator device contained composition pH about 3 to 5
• Claim 25: method composition pH about 3 to 5

These are common levers for nasal formulations (acidic pH to stabilize peptide and tolerability). If an accused product stays within pH range but uses a different acid/base system, it may still land within claims 2 and 3 but avoid claim 4’s specific “means” limitation.

Osmotic pressure: claims 5 and 27

• Claim 5: osmotic pressure about 260 to 380 mOsm/L
• Claim 27: same limitation in method claim

This is a formulation constraint that is likely product-specific; even slight deviations can avoid depending claims if the asserted claim is parameter-dependent.

Viscosity: claim 6

• Claim 6: viscosity less than 2 × 10^-3 Pa·s

This can be used to differentiate from higher-viscosity nasal liquids that improve residence time. If an accused product has higher viscosity, it can avoid claim 6 while potentially still infringing claim 1.

BAK concentration: claims 21 and 29

• Claim 21: BAK 0.002% to 0.02% w/v
• Claim 29: same in method claim
• Claim 1 itself does not state the numeric concentration, only “effective amount.”

Practical impact:

• A product with BAK outside the numeric range can still infringe claim 1 if BAK is present in an “effective amount,” but it can avoid the dependent numeric claims if the patentee asserts only parameter-specific claims.

Non-ionic surfactant options: claims 16-19 and 30-33

• Claim 16: further comprises a non-ionic surfactant
• Claim 17: surfactant is a polyoxyalkylene ether
• Claim 18: the ether is polyoxyethylene ether, polyoxypropylene ether, or polyoxyalkylene higher alcohol ether
• Claim 19: higher alcohol ethers limited to:
  • polyoxyethylene lauryl ether
  • polyoxyethylene cetyl ether
  • polyoxyethylene cholesteryl ether
  • polyoxypropylene lauryl ether
  • polyoxypropylene cetyl ether
  • polyoxypropylene cholesteryl ether
  • mixtures thereof

Parallel surfactant dependent limitations exist in method claims 30-33.

So, surfactant selection creates both an infringement risk and a design-around knob:

• Avoid adding any non-ionic surfactant to escape claims 16-19
• Or choose a surfactant outside the listed “polyoxyalkylene ether” class or outside the listed higher alcohol ethers

Carrier: claim 15 and 24 and 35

• Claim 15: aqueous saline
• Claims 24 and 35: same constraint in device/method dependent claims

Claim 1 only requires an “aqueous liquid nasal carrier,” so an accused product using saline is at risk for dependent claims; an alternative aqueous carrier could avoid claim 15/24/35 while still meeting claim 1’s carrier requirement.

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What is the dose/concentration scope (MRC units/mL)?

The patent includes multiple dependent claims tying the calcitonin concentration to specific numeric windows:

• Claim 11: 100 to 8,000 MRC units/mL
• Claim 12: 500 to 4,000
• Claim 13: 500 to 2,500
• Claim 14: 1,000 to 2,000
• Parallel constraints:
  • Claim 23: applicator device contains 500 to 4,000
  • Claim 34: method composition contains 500 to 4,000

Coverage implication:

• If an accused product uses calcitonin concentrations within 500–4,000 MRC units/mL, it can trigger multiple dependent claims.
• If it uses outside those windows, claim 1 still remains plausible because claim 1 uses “therapeutically effective amount” without numeric limits.

The concentration windows can become focal in litigation because they let a court or expert evaluate infringement via product specs and stability/formulation records.

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How do claim dependencies interact: which combinations create the highest infringement risk?

Highest-risk infringement map (likely assert targets)

If an accused product uses:

• calcitonin from the enumerated list,
• BAK in an effective amount,
• aqueous nasal carrier, and also has typical nasal formulation parameters (acid pH, controlled osmolality, low viscosity), then the patent’s independent claim 1 plus multiple dependent claims may stack.

Key “stacking” opportunities for the patentee:

• pH within 3-5 and possibly 3.5-4.5
• osmotic pressure 260-380 mOsm/L
• viscosity below 2×10^-3 Pa·s
• BAK concentration 0.002%-0.02% w/v
• presence of polyoxyalkylene ethers in the listed subtypes
• calcitonin concentration within one of the numeric windows

Design-around levers that matter in this claim set

1. Avoid BAK entirely or use a non-BAK strategy (stabilizer/enhancer) so claim 1’s “benzalkonium chloride” element is missing.
2. If BAK is unavoidable, try to land outside the numeric BAK range in claims 21/29; this may avoid dependent claims but not necessarily claim 1.
3. Move pH outside claimed windows (claims 2/3) and osmotic pressure outside 260-380 mOsm/L (claims 5/27) to reduce dependent claim exposure.
4. Avoid listed surfactants or avoid non-ionic surfactants altogether to defeat claims 16-19/30-33.
5. Use an aqueous carrier that is not “aqueous saline” to avoid claim 15/24/35, while preserving general “aqueous carrier” for claim 1 risk analysis.

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What patents would typically overlap with US 5,733,569 in the calcitonin nasal space?

Claim-element-based overlap zones

In the calcitonin nasal formulation space, other patents commonly claim one or more of:

• calcitonin nasal formulations (peptide + nasal vehicle)
• nasal absorption enhancers (including quaternary ammonium compounds like BAK)
• preservatives and tonicity buffering
• delivery devices (sprays, aerosols, applicators, pumps)
• peptide stabilization at low pH and controlled osmolality
• viscosity modifiers and surfactants

Given US 5,733,569’s specific combination of:

• calcitonin species list
• BAK as enhancer
• aqueous nasal carrier
• and dependent physicochemical windows,

overlapping patents are likely those that claim either:

• formulations with calcitonin + BAK (direct overlap), or
• calcitonin nasal sprays with similar pH/osmolality/viscosity even without BAK, or
• device claims tied to aqueous nasal sprays, or
• methods of administering calcitonin intranasally with absorption enhancement.

Landscape intensity drivers

• The enumerated calcitonin list means overlap is strongest where formulations use salmon calcitonin (most common historically in intranasal products).
• The BAK numeric range creates a “narrow corridor” for secondary infringement risk among later reformulations that retained BAK to improve bioavailability.

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What is the infringement hook: how strong is US 5,733,569’s claim coverage?

Strength factors

• Independent claim 1 is not limited to a specific pH, osmolality, viscosity, dose concentration, surfactant, or carrier composition beyond “aqueous nasal carrier.”
• It is also not restricted to a specific BAK percentage, which can matter if an accused product argues its BAK amount is not “effective,” but BAK-based enhancement is usually measurable in nasal PK or stability/absorption studies.

Vulnerabilities in claim construction

• The formulation is limited to calcitonin chosen from an enumerated set. A product that uses a calcitonin analog outside that list could avoid claim 1.
• The “enhance bioavailability … when administered to nasal mucosa” can invite argument about functional limitation proof. In practice, such language often gets treated as result-oriented but tied to known roles of BAK.

Enforcement breadth

The claim set’s coverage of:

• composition
• device containing composition
• method of administering allows the patentee to pursue multiple theories against different actors (manufacturer, device packager, or labeler).

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US commercial and regulatory context that typically drives challenges to this patent type

While this analysis focuses on claim scope, the regulatory posture that usually drives freedom-to-operate disputes for intranasal peptide products is:

• whether a follow-on entrant will file an ANDA-like pathway (if applicable) or a different regulatory pathway for complex generics
• whether bioequivalence studies include nasal absorption enhancers
• whether the product label specifies intranasal use and contains preservatives (BAK)

For litigation strategy, the key is not the therapeutic indication alone. It is the formulation package that contains BAK and matches the claimed vehicle and parameters.

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Timeline and exclusivity: what does the patent date imply for current risk?

No reliable expiration or Orange Book status can be derived from the claim text alone. A complete exclusivity/timeline analysis requires confirmed priority data, issue date, and any listed FDA drug product(s), none of which is provided in the input. Per the constraints here, no timeline assertions are included.

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Key takeaways

• US 5,733,569 is a calcitonin nasal spray formulation patent centered on BAK-mediated bioavailability enhancement in an aqueous nasal carrier.
• Independent claim 1 covers composition-level manufacture and includes calcitonin limited to four enumerated species plus “effective amount” BAK.
• Dependent claims add increasingly specific constraints on pH (3-5; 3.5-4.5), osmotic pressure (260-380 mOsm/L), viscosity (<2×10^-3 Pa·s), BAK concentration (0.002%-0.02% w/v), optional non-ionic surfactants (polyoxyalkylene ether subclasses), and calcitonin concentration in MRC units/mL.
• The patent also extends to applicator device (claims 7-8) and a method of administration (claim 9), increasing enforcement surface area.

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FAQs

1. Can a product avoid US 5,733,569 by using a different absorption enhancer than benzalkonium chloride?
   If benzalkonium chloride is absent, the claim element tied to BAK is missing for claims requiring it.

2. Does matching the pH window alone create infringement risk under US 5,733,569?
   No. pH-dependent claims are dependent; infringement generally still requires claim 1 elements including calcitonin list and BAK.

3. If a product uses BAK outside 0.002%-0.02% w/v, does it avoid the numeric-dependent claims?
   It can avoid claims 21/29, but claim 1 may still be asserted because claim 1 does not require the numeric BAK window.

4. How do device and method claims change litigation targets?
   Claim 7 reaches device/application packaging systems containing the formulation, and claim 9 reaches the act of administering intranasally using the claimed formulation.

5. What formulation changes most directly reduce exposure across multiple dependent claims?
   Avoid adding any non-ionic surfactant (to defeat claims 16-19/30-33) and use non-saline aqueous carriers (to defeat claims 15/24/35), while also moving pH/osmolality/viscosity outside the dependent windows.

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References

1. US Patent 5,733,569, “Liquid pharmaceutical composition and a device for administering calcitonin,” claims as provided in the prompt.

Drugs Protected by US Patent 5,733,569

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: 5,733,569

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8228390	Oct 05, 1982
Japan	8236928	Dec 30, 1982
United Kingdom	8320865	Aug 03, 1983
United Kingdom	8322528	Aug 22, 1983

International Family Members for US Patent 5,733,569

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	394947
Austria	402895
Austria	A259288
Austria	A349483