US Patent 4,760,072: Nedocromil Sodium Claims, Scope, Expiration, and Patent Landscape

US Patent 4,760,072 protects a specific crystalline, hydrated form of nedocromil sodium, together with particle characteristics, a chlorofluorocarbon-based pressurized inhalation formulation, and an inhaled treatment method. The patent issued on July 26, 1988, and its 17-year term expired on July 26, 2005. The claims therefore no longer create an enforceable US patent barrier. Their technical limitations remain relevant to historical formulation design, prior-art analysis, freedom-to-operate reviews, and invalidity assessments.

What does US Patent 4,760,072 cover?

The patent covers four related subject-matter groups:

A crystalline solid form of nedocromil sodium containing bound water.
Specific chemical and physical characteristics of that solid.
A pressurized metered-dose inhalation formulation using the crystalline material.
A method of treating reversible obstructive airway disease by inhaling the material.

The patent is narrower than a basic compound patent. It does not claim nedocromil sodium in every physical or chemical form. It requires a crystalline solid with defined hydration characteristics and, for several dependent claims, specified color, diffraction, infrared, particle-size, morphology, or propellant properties.

The patent appears directed to the development of a stable, inhalable nedocromil sodium product rather than to the underlying discovery of the nedocromil molecule itself.

What are the key bibliographic and legal dates for US 4,760,072?

Item	Information
US patent number	4,760,072
Subject	Crystalline nedocromil sodium and inhalation formulations
Assignee shown on patent record	Fisons plc
Filing period	Mid-1980s US application
Earliest priority	1984, according to the patent family record
Issue date	July 26, 1988
Original US patent term	17 years from issue
Estimated ordinary expiration	July 26, 2005
Current enforceability	Expired
Relevant dosage form	Pressurized inhalation aerosol
Relevant therapeutic use	Reversible obstructive airway conditions

The patent predates the Uruguay Round Agreements Act changes that generally shifted US utility patent terms to 20 years from the earliest effective nonprovisional filing date. For this patent, the 17-year-from-issue framework governs the ordinary term. No later patent-term extension is apparent from the patent’s historical record.

How broad is claim 1 for crystalline nedocromil sodium?

Claim 1 is the principal composition claim. It covers:

solid nedocromil sodium;
in crystalline form; and
containing bound water as determined by thermogravimetric analysis.

The claim does not recite a numerical water range. That limitation appears in claim 2. Claim 1 therefore establishes the broadest claimed form within the patent, but its breadth is constrained by the requirement that the material be both crystalline and hydrated.

Claim 1 construction

A potentially infringing material would generally need to satisfy each of these limitations:

Limitation	Technical significance
Solid	Excludes solutions and potentially non-solid compositions
Nedocromil sodium	Requires the sodium salt, not necessarily another salt or free acid
Crystalline	Requires an ordered solid-state form
Bound water	Requires water associated with the crystal structure or solid form
TGA determination	Makes thermogravimetric analysis the specified analytical basis

The claim does not expressly require a particular crystal habit, polymorph designation, color, particle size, or inhaler formulation. Those restrictions appear in dependent claims.

A material that is amorphous, anhydrous, or merely contains adventitious surface moisture would present a stronger non-infringement position against claim 1, subject to the analytical evidence and claim construction applied in a particular proceeding.

What hydration range is protected by claims 2 and 3?

Claim 2 narrows claim 1 to crystalline nedocromil sodium containing 3.0% to 4.0% w/w bound water. Claim 3 narrows the composition further to 3.5% bound water.

Claim	Hydration limitation
1	Bound water determined by TGA; no numerical range
2	3.0% to 4.0% w/w bound water
3	3.5% bound water

Claim 3 is not limited to a particular manufacturing process. It is a product claim defined by the measured water content. The practical scope depends on the analytical method, sample preparation, TGA conditions, and whether “3.5%” is construed as exact or subject to ordinary measurement tolerance.

A competing manufacturer could attempt to design around claims 2 and 3 by producing an anhydrous form, an amorphous form, or a crystalline form outside the 3.0% to 4.0% range. That strategy would not automatically avoid claim 1, which lacks the numerical range.

What do the color, X-ray diffraction, and infrared claims protect?

Claims 4 through 7 add analytical and physical specifications.

Color limitations

Claim 4 requires powder form and a Lovibond yellow reading below 2.0 when the material contains 10% w/w water. Claim 5 narrows that range to 0.8 to 1.8.

These claims target a relatively low-color, clean crystalline product. The claim language makes the test condition material: the Lovibond value is measured after the sample contains 10% water.

Powder X-ray diffraction

Claim 6 requires a crystalline powder X-ray diffraction pattern. It does not identify specific diffraction peaks in the claim text provided. That makes the claim less precise than a claim listing a peak set or a reference pattern.

The likely dispute would concern whether the tested material produces a pattern sufficiently characteristic of crystalline nedocromil sodium and whether the patent specification supplies an identifiable reference standard.

Infrared spectrum

Claim 7 requires an infrared spectrum showing a shoulder at 3500 cm-1 when total water content is 10% w/w. The shoulder is an additional structural or hydration marker.

Claim	Added limitation
4	Powder; Lovibond yellow below 2.0 at 10% water
5	Lovibond yellow between 0.8 and 1.8
6	Crystalline powder X-ray diffraction pattern
7	Infrared shoulder at 3500 cm-1 at 10% total water

These claims are narrow and evidence-intensive. Enforcement would likely require validated analytical testing and careful control of sample conditioning.

What inhalation formulation is protected by claims 8 through 12?

Claim 8 claims an inhalation formulation for a reversible obstructive airway condition comprising:

a pharmaceutically acceptable liquefied gas propellant;
crystalline hydrated nedocromil sodium within claim 1;
a mass median diameter below 4 microns; and
an amount effective for treatment.

Claim 9 further requires:

no more than 5% by weight of particles above 10 microns; and
at least 90% by weight of particles below 6 microns.

Claim 10 requires 0.5% to 10% by weight of finely divided nedocromil sodium.

Claim 11 specifies a mixture of propellants 12 and 114, with propellant 12 to propellant 114 in a ratio from 2:1 to 1:1 by weight. These are dichlorodifluoromethane and dichlorotetrafluoroethane, respectively.

Claim 12 adds sorbitan trioleate.

Claim	Formulation scope
8	Hydrated crystalline nedocromil sodium in liquefied gas aerosol; MMD below 4 µm
9	Particle distribution limits
10	0.5% to 10% drug concentration
11	Propellants 12 and 114 at a 2:1 to 1:1 ratio
12	Sorbitan trioleate added to claim 11

The formulation claims are materially narrower than a general inhaled nedocromil sodium claim. A dry-powder inhaler, nebulized aqueous solution, or hydrofluoroalkane aerosol would not literally satisfy the express propellant limitations of claims 8 through 12 unless the claim language were interpreted unusually broadly.

What particle morphology is covered by claims 13 and 14?

Claims 13 and 14 address needle-shaped particles.

Claim 13 requires nedocromil sodium within claim 1 in the form of needles having:

breadth of 1.5 to 3.5 microns; and
length-to-breadth ratio of up to 10:1.

Claim 14 narrows the breadth to 1.5 to 2.5 microns.

Claim	Particle morphology
13	Needles, 1.5 to 3.5 µm breadth, length-to-breadth ratio up to 10:1
14	Needles with 1.5 to 2.5 µm breadth

These limitations connect crystal morphology to aerosol performance. The claims require more than a particle-size distribution. They require a needle morphology and dimensional measurements. Particle imaging methodology, orientation, sampling, and aggregation would be central to any technical comparison.

What treatment method is protected by claim 15?

Claim 15 covers treating a mammal suffering from a reversible obstructive airway condition by administering an effective amount of solid crystalline nedocromil sodium according to claim 1 by inhalation.

The claim requires:

a mammalian patient;
a reversible obstructive airway condition;
inhaled administration;
an effective amount; and
the crystalline hydrated nedocromil sodium of claim 1.

The method claim is not limited to the CFC formulation in claim 8. A formulation using a different delivery platform could potentially fall within claim 15 if it delivers the claimed solid form by inhalation. Because the patent expired in 2005, claim 15 has no current US enforcement value.

How do the claims relate to one another?

The claim hierarchy creates two main infringement pathways.

Composition pathway

Claims 1 through 7 and 13 through 14 depend on the physical identity of the drug substance. A product could fall within claim 1 without meeting the narrower color, hydration, spectral, or morphology limitations.

Formulation pathway

Claims 8 through 12 require the composition of claim 1 and add aerosol limitations. A formulation that uses the claimed crystalline drug but does not use the specified liquefied propellant or particle distribution may avoid those formulation claims while potentially implicating claim 1 during the patent term.

Method pathway

Claim 15 covers inhaled use of the claim 1 material. It is broader in delivery technology than claims 8 through 12, but narrower in requiring treatment of the specified airway condition.

When did US Patent 4,760,072 lose exclusivity?

The patent lost ordinary US patent exclusivity on July 26, 2005. No current patent-term barrier should remain based on this patent.

The following distinctions matter:

Exclusivity type	Status
Patent exclusivity under US 4,760,072	Expired
Small-molecule regulatory exclusivity	Historical and expired
Current formulation exclusivity from this patent	None
Current method-of-use exclusivity from this patent	None
Biosimilar exclusivity	Not applicable
Current Orange Book blocking effect	None from this expired patent

Patent expiration does not remove the patent from historical prior-art records. It only ends the right to exclude others based on the patent.

What was the FDA and Orange Book status of nedocromil sodium?

Nedocromil sodium was marketed in the US as Tilade inhalation aerosol for maintenance treatment and prevention of asthma symptoms. The product was an inhaled small molecule delivered through a pressurized metered-dose inhaler.

FDA product records identify Tilade as an approved inhalation aerosol product. The product’s historical CFC-based delivery system became commercially and regulatorily obsolete as CFC use was phased out under US environmental requirements. FDA’s Orange Book distinguishes approved products from discontinued products and does not create an active exclusivity right for an expired patent.[1][2]

There is no biosimilar pathway for nedocromil sodium because it is a chemically synthesized small molecule, not a biological product. Any modern competitor would use the abbreviated new drug application pathway if an eligible reference product and commercially supportable formulation existed.

Were there Paragraph IV challenges to US 4,760,072?

No material current Paragraph IV risk remains because the patent expired in 2005. Any historical ANDA certification would no longer delay approval based on this patent.

The public record does not establish a commercially significant, continuing Paragraph IV dispute directed specifically to US 4,760,072. A Paragraph IV challenge would have been relevant only before expiration and only if the patent was listed against an applicable reference product.

A patent challenge could have targeted:

lack of novelty over earlier nedocromil sodium solid forms;
obviousness of crystallization and hydration control;
indefiniteness of “bound water,” “shoulder,” “crystalline,” or analytical thresholds;
enablement of the specified aerosol particle characteristics;
non-infringement based on an alternative solid form or propellant.

What patent landscape surrounded nedocromil sodium?

The relevant landscape included more than US 4,760,072.

Underlying compound and salt protection

Earlier patent families likely addressed the nedocromil chemical entity, salts, intermediates, or therapeutic activity. Those rights would have had separate expiration dates and claim scopes. US 4,760,072 should not be treated as the basic nedocromil compound patent.

Solid-state and formulation protection

US 4,760,072 targeted:

crystalline hydration;
color control;
particle morphology;
aerosol particle-size distribution;
CFC propellant ratios; and
suspension stabilization with sorbitan trioleate.

These are typical secondary patent categories used to protect a commercial inhaler after the core compound disclosure.

Regulatory and environmental constraints

The CFC limitations became a commercial weakness. Even if the claims had remained unexpired, a product relying on propellants 12 and 114 would have faced regulatory and market barriers because of CFC phaseout requirements. Modern inhalers generally use hydrofluoroalkane or other delivery technologies, which may fall outside the literal scope of claims 8 through 12.

Competitive therapies

Nedocromil competed with cromolyn sodium, inhaled corticosteroids, leukotriene modifiers, and bronchodilator-based asthma therapies. Its commercial position weakened as inhaled corticosteroids became the dominant anti-inflammatory maintenance treatment for asthma.

How strong was the patent estate for nedocromil sodium?

The estate was technically layered but commercially time-limited.

Factor	Assessment
Core compound coverage	Not established by US 4,760,072
Crystalline-form coverage	Specific and potentially meaningful during term
Hydration coverage	Defined broadly in claim 1, narrowly in claims 2 and 3
Formulation coverage	Narrow because of CFC and particle-size limitations
Method-of-use coverage	Broad delivery format, but limited to claim 1 material
Design-around potential	Significant through anhydrous, amorphous, alternative crystal, or non-CFC forms
Current enforceability	None
Biosimilar barrier	None
Commercial relevance today	Historical and technical rather than exclusionary

The most defensible historical value likely rested in the combination of crystalline form, controlled hydration, and inhalable particle engineering. The weakest practical area was the CFC-specific formulation coverage, given the transition away from propellants 12 and 114.

What generic launch risks exist today for nedocromil sodium?

The patent-specific generic launch risk from US 4,760,072 is zero because the patent expired. A modern entrant would instead face regulatory, manufacturing, and commercial issues.

Regulatory risk

A new product would need an approved FDA pathway, appropriate clinical or bioequivalence support, and a viable reference-product strategy. If the original reference product is discontinued or difficult to use for comparative testing, the development pathway may become less straightforward.

Manufacturing risk

The most demanding technical elements are:

reproducible crystalline-state control;
bound-water consistency;
low-color drug substance;
controlled needle morphology;
respirable aerodynamic particle-size distribution;
suspension stability; and
device compatibility.

These are manufacturing barriers, not surviving patent barriers.

Commercial risk

Nedocromil is an older asthma therapy with substantial competition from inhaled corticosteroids, combination inhalers, leukotriene modifiers, and newer device technologies. A generic or reformulated product would need a clear clinical, device, supply, or pricing advantage.

How does US 4,760,072 compare with modern inhaler patents?

US 4,760,072 is a product-and-formulation patent built around a CFC suspension aerosol. Modern inhaler portfolios more commonly claim:

hydrofluoroalkane formulations;
device and actuator geometry;
co-suspension systems;
particle engineering;
inhaler dose counters;
dry-powder carrier systems;
nebulizer platforms; and
combinations with corticosteroids or bronchodilators.

The older patent’s crystalline drug-substance claims are more portable across delivery systems than its CFC formulation claims. Claims 8 through 12 are closely tied to the technology used in the original product, while claims 1 and 15 could have reached alternative inhalation systems during the patent term if the claimed solid form was used.

What patent litigation and settlement agreements affected this patent?

There is no identified active US litigation or settlement agreement that currently affects US 4,760,072. Any historical litigation would have ended with patent expiration, dismissal, judgment, or settlement and would not restore exclusivity.

A complete litigation analysis should distinguish:

cases naming US 4,760,072 directly;
cases involving other nedocromil patents;
ANDA litigation concerning Tilade;
product-liability cases; and
disputes over CFC-to-non-CFC reformulation.

The patent number alone does not establish that a particular nedocromil litigation record concerns the claims analyzed here.

What is the revenue exposure associated with US 4,760,072?

No current revenue is protected by this patent. Any historical revenue exposure ended no later than patent expiration in 2005.

Commercial exposure during the patent term would have included:

the branded Tilade inhalation aerosol;
crystalline nedocromil sodium supply;
metered-dose inhaler manufacturing;
propellant and surfactant formulation know-how; and
potential follow-on inhalation products.

Public sources do not provide a reliable patent-attributed revenue figure for US 4,760,072. Product sales cannot be assigned to this patent without separating compound, regulatory, formulation, trademark, manufacturing, and distribution rights.

Key Takeaways

US 4,760,072 claims a crystalline hydrated form of nedocromil sodium, not nedocromil sodium in every form.
Claim 1 is the central composition claim and requires crystallinity plus bound water measured by TGA.
Claims 2 and 3 specify 3.0% to 4.0% and 3.5% bound water, respectively.
Claims 4 through 7 add color, X-ray diffraction, and infrared limitations.
Claims 8 through 12 cover a CFC-based pressurized aerosol with defined particle sizes, propellant ratios, and sorbitan trioleate.
Claims 13 and 14 protect needle-shaped particle morphology.
Claim 15 covers inhaled treatment of reversible obstructive airway disease using the claimed solid form.
The patent issued July 26, 1988, and expired July 26, 2005.
No current Paragraph IV, biosimilar, Orange Book, or litigation barrier arises from this patent.
Its remaining importance is historical, technical, and relevant to prior-art and freedom-to-operate analysis.

FAQs About US Patent 4,760,072 and Nedocromil Sodium

Does US 4,760,072 still block a generic nedocromil inhaler?

No. The patent expired on July 26, 2005, so it cannot block a current US generic or reformulated inhaler.

Can an anhydrous nedocromil sodium product avoid the patent claims?

An anhydrous product would have a strong basis to avoid claims requiring bound water, but that issue was relevant only before the patent expired.

Does the patent cover hydrofluoroalkane nedocromil inhalers?

Claims 8 through 12 expressly identify CFC propellants 12 and 114. A hydrofluoroalkane formulation would generally fall outside those specific formulation limitations, although claim 15 was not limited to those propellants.

Is nedocromil sodium eligible for a biosimilar application?

No. Nedocromil sodium is a chemically synthesized small molecule. A competing product would generally use an abbreviated new drug application or another small-molecule regulatory pathway.

What is the most commercially important technical teaching in US 4,760,072?

The most important technical teaching is the use of a controlled crystalline, hydrated nedocromil sodium solid with respirable particle characteristics suitable for suspension aerosol delivery.

References

U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
U.S. Patent No. 4,760,072. (1988). Nedocromil sodium. U.S. Patent and Trademark Office. https://patents.google.com/patent/US4760072A/en
U.S. Environmental Protection Agency. (n.d.). Class II ozone-depleting substances. https://www.epa.gov/ozone-layer-protection/class-ii-ozone-depleting-substances

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8409705	Apr 13, 1984
United Kingdom	8423634	Sep 19, 1984

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	69230	⤷ Start Trial
Australia	4094285	⤷ Start Trial
Australia	584329	⤷ Start Trial
Belgium	902185	⤷ Start Trial
Canada	1257201	⤷ Start Trial
Switzerland	667271	⤷ Start Trial
Germany	3584580	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 4,760,072