United States Patent 4,395,421: Scope, Claims, Expiration, and Patent Landscape for Disodium Cromoglycate

U.S. Patent No. 4,395,421 protects specific physical forms and oral or intranasal dosage presentations of disodium cromoglycate, also known as cromolyn sodium. The patent does not broadly claim the molecule itself. Its principal limitations are wet-granulated manufacture, bulk density, particle-size distribution, excipient content, water content, capsule fill, and selected antiallergic uses.

The patent issued on July 26, 1983. Based on the former 17-year term measured from grant, the ordinary patent term would have ended in 2000, subject to any patent-term adjustment or other term calculation applicable to the record. The patent is therefore expired and does not present a current U.S. blocking right. Its claims remain relevant for prior-art, validity, freedom-to-operate, and historical product-development analysis.

What does U.S. Patent 4,395,421 claim?

The claims cover four related subject areas:

A physically defined granular form of disodium cromoglycate.
Unit dosage forms containing that granular material.
Capsule and moisture-content characteristics.
Oral or intranasal treatment of allergic gastrointestinal and nasal disorders.

The patent is narrower than a composition patent directed to all cromolyn sodium. A product that contains cromolyn sodium but is not made by the claimed process, does not satisfy the specified physical characteristics, or falls outside the dosage limitations would not automatically fall within the claims.

Claim-by-claim scope

Claim	Subject matter	Principal limitations	Scope assessment
1	Granular disodium cromoglycate	Produced by wet granulation; bulk density 0.34-0.70 g/mL; less than 5 wt.% other compound, excluding water	Core product claim; requires process and physical-property limitations
2	Preferred granular form	Claim 1; bulk density 0.53-0.66 g/mL	Narrower density range
3	Hard granular form	Claim 1; hard granular form	Adds a qualitative structural limitation
4	Essentially pure product	Claim 1; no other compound except water	Narrower than claim 1 because the less-than-5% impurity allowance is removed
5	Coarse-particle limitation	Claim 1; less than 20 wt.% of particles above 200 microns	Particle-size distribution limitation
6	Fine-particle limitation	Claim 1; no more than 60 wt.% below 60 microns	Relatively broad fine-particle limitation
7	Tighter fine-particle limitation	Claim 1; less than 20 wt.% below 60 microns	Narrower than claim 6
8	Unit dosage form	1-250 mg disodium cromoglycate; wet granulation; bulk density 0.45-0.70 g/mL; less than 5 wt.% other compound except water	Product presentation claim
9	Lubricant-free dosage form	Claim 8; no lubricant	Narrows claim 8
10	Capsule fill	Claim 8 or 9; capsule 60-80% full when loosely filled	Adds a physical packaging limitation
11	Moist granular dosage form	More than 10 wt.% granular cromoglycate; density 0.45-0.70 g/mL; water 5-12 wt.%; encapsulating material 35-85 wt.%	Complex formulation and moisture-content claim
12	High active loading	Claim 11; more than 50 wt.% granular cromoglycate	Narrows claim 11
13	Gastrointestinal treatment	Oral administration for allergic gastrointestinal disorders	Method-of-use claim
14	Nasal treatment	Intranasal administration for allergic nasal disorders	Method-of-use claim

How strong is the patent estate for disodium cromoglycate?

The estate reflected by U.S. Patent 4,395,421 was technically focused rather than molecule-wide. Its strength came from converting a difficult-to-handle active pharmaceutical ingredient into a defined granular material suitable for oral or inhaled administration.

The strongest historical protection likely centered on the combination of:

Wet granulation;
Defined bulk density;
High disodium cromoglycate content;
Controlled particle-size distribution;
Capsule-fill characteristics;
Limited or no lubricant; and
Defined water content.

A competitor could potentially avoid the claims by using a different manufacturing route, such as dry granulation, roller compaction, spray drying, direct compression, fluid-bed agglomeration, or another process that did not satisfy the wet-granulation limitation. Avoidance would depend on the claim construction and on whether the resulting product was considered materially indistinguishable from the patented product.

Claims 13 and 14 are method claims. They are limited to treatment of allergic gastrointestinal or nasal disorders using the claimed form of disodium cromoglycate. They do not claim every therapeutic use of cromolyn sodium.

Does claim 1 cover all cromolyn sodium products?

No. Claim 1 requires all of the following:

Disodium cromoglycate;
Production by wet granulation;
Bulk density from 0.34 to 0.70 g/mL; and
Less than 5% by weight of any other compound, excluding water.

The claim does not cover a conventional cromolyn sodium solution, an aerosol formulation, a nasal spray, or a powder that falls outside the stated density and composition limits merely because the product contains the same active ingredient.

The phrase “produced by wet granulation” creates an important product-by-process issue. U.S. courts generally treat product-by-process language as part of the claim for infringement analysis, although the product itself must satisfy the product limitations. In Abbott Laboratories v. Sandoz, Inc., the Federal Circuit explained that a product-by-process limitation may restrict the scope of a claim even where the final product is chemically indistinguishable from a product made by another process.[1] The precise effect depends on claim construction and the governing infringement theory.

What formulations are protected by the patent?

The formulation claims focus on solid or granular dosage forms.

Granular active pharmaceutical ingredient

Claims 1-7 cover granular disodium cromoglycate with specified physical properties. The claimed material may contain water, but the allowance for other compounds is tightly controlled:

Claim 1 allows less than 5 wt.% of other compounds.
Claim 4 requires none of any other compound except water.
Claims 5-7 impose particle-size restrictions.
Claims 2 and 3 impose preferred density or physical-form limitations.

The claims therefore target a substantially active-rich granular material rather than a conventional tablet formulation containing a large proportion of fillers, binders, lubricants, or disintegrants.

Unit dosage forms

Claim 8 covers a unit dosage containing 1 to 250 mg of the wet-granulated active. The density range is narrower than in claim 1, beginning at 0.45 g/mL.

Claim 9 excludes lubricants. This limitation appears directed to avoiding a conventional tableting or capsule-processing excipient that might interfere with dissolution, dispersion, or device delivery.

Claim 10 adds a capsule-fill limitation. The capsule must be 60-80% full when loosely filled. This is a physical presentation limitation, not merely a statement of capsule size.

Moisture-containing encapsulated material

Claim 11 is materially different from claims 8-10. It requires:

More than 10 wt.% granular disodium cromoglycate;
Bulk density from 0.45 to 0.70 g/mL;
5-12 wt.% water; and
35-85 wt.% encapsulating material.

Claim 12 requires more than 50 wt.% granular disodium cromoglycate and is therefore directed to a higher-active-load embodiment.

The wording of claim 11 should be assessed carefully because its stated ranges do not necessarily add to 100%. That drafting structure may permit a residual quantity of additional ingredients unless excluded by another limitation or by the specification. In a historical infringement analysis, the identity and function of the “encapsulating material” would require close review.

What particle-size characteristics are claimed?

Claims 5-7 create alternative particle-size profiles:

Claim 5 limits the coarse fraction: less than 20% of particles may exceed 200 microns.
Claim 6 limits the fine fraction: no more than 60% may be below 60 microns.
Claim 7 imposes a tighter fine-fraction limit: less than 20% may be below 60 microns.

These limitations matter because bulk density and particle-size distribution can be tested independently. A product may satisfy the bulk-density range while failing one or more particle-size limitations. Conversely, a product could meet the particle-size profile but fail the wet-granulation or purity requirement.

The patent does not state in the claims how particle diameter is measured, what sampling protocol applies, or whether the percentages are based on mass, volume, or particle count. Claim 5 expressly uses weight percentage. Claims 6 and 7 state “by weight,” so analytical testing would need to follow a reproducible sieve or equivalent particle-size method.

What is the scope of the unit dosage claims?

The unit dosage claims are narrower than a general formulation claim because they combine amount, manufacturing process, physical density, composition, and packaging limitations.

Claim 8

Claim 8 requires:

A unit dosage form;
1-250 mg of disodium cromoglycate;
Wet-granulated production;
Granular bulk density of 0.45-0.70 g/mL; and
Less than 5 wt.% other compound, excluding water.

The dosage range is broad enough to encompass low-dose nasal or inhaled presentations and higher-dose oral products, but the claim still depends on the specified granular material.

Claim 9

Claim 9 adds the absence of lubricant. A formulation with magnesium stearate, stearic acid, sodium stearyl fumarate, or another lubricant would present a potential non-infringement position if the absence of lubricant is construed as a mandatory limitation.

Claim 10

Claim 10 requires the capsule to be 60-80% full when loosely filled. The phrase “loosely filled” may raise evidentiary issues because capsule fill depends on vibration, tapping, settling, equipment, and measurement protocol. A claim construction or infringement analysis would likely require evidence concerning the patent specification and the industry meaning of the term at the relevant time.

What method-of-use patents are present?

Claims 13 and 14 are method-of-use claims.

Gastrointestinal allergy treatment

Claim 13 covers oral administration to alleviate symptoms of an allergic gastrointestinal disorder. The claim requires:

A patient suffering from the specified condition;
Oral administration;
An effective amount; and
Disodium cromoglycate meeting claim 1.

This claim is not a general claim to treating gastrointestinal disease. It is limited to disorders in which an allergic reaction is involved.

Intranasal allergy treatment

Claim 14 covers intranasal administration for an allergic nasal disorder. It similarly depends on the claimed disodium cromoglycate form.

The method claims may have been commercially relevant to oral cromolyn products and nasal cromolyn products, but their practical enforceability would have depended on evidence of the claimed product form, the indicated disease, administration route, and direct or induced infringement.

When did U.S. Patent 4,395,421 lose exclusivity?

U.S. Patent 4,395,421 issued on July 26, 1983.[2] For a patent subject to the pre-1995 U.S. patent-term regime, the ordinary term was 17 years from grant. On that basis, the ordinary expiration date was July 26, 2000.

Event	Date or status
Patent issued	July 26, 1983
Ordinary former U.S. term	17 years from grant
Ordinary calculated expiration	July 26, 2000
Current status	Expired
Current enforceability	No ordinary enforceable exclusionary right from this patent

Patent-term adjustment and patent-term extension rules should be checked against the official USPTO record when a historical damages or launch-date analysis depends on the exact final day of enforceability. The patent’s age makes current blocking-right risk immaterial even if a term calculation produced a limited variation from the ordinary date. The patent cannot create a present Paragraph IV obstacle for a new cromolyn sodium applicant.

What is the FDA and Orange Book status of cromolyn sodium?

Cromolyn sodium is the disodium salt of cromoglycic acid and is also called disodium cromoglycate. U.S. products historically included:

Intal, an inhalation product associated with Fisons;
NasalCrom, an intranasal cromolyn product; and
Generic cromolyn sodium products and other dosage forms.

The FDA Orange Book lists approved drug products and relevant patent or exclusivity information for eligible products.[3] A product-specific Orange Book review is required because listing status can differ by dosage form, route, applicant, and product history. U.S. Patent 4,395,421, issued in 1983 and ordinarily expiring in 2000, is not a current Orange Book patent barrier.

Cromolyn sodium is a small-molecule drug, not a biologic. Biosimilar litigation and the Biologics Price Competition and Innovation Act pathway therefore do not apply. Any current competition would proceed through an abbreviated new drug application, a 505(b)(2) application, or a full new drug application, depending on the product and reference-product position.

Which companies have challenged or competed with the patent?

The patent was associated with an older cromolyn sodium product landscape rather than a current branded-generic patent dispute. The relevant historical commercial participants included:

Company or product	Relevance
Fisons	Historical developer and marketer associated with Intal
Aventis/Sanofi successor operations	Historical commercial successor context for certain cromolyn products
King Pharmaceuticals	Associated with NasalCrom commercialization
Bayer Consumer Health	Historical commercialization of NasalCrom in consumer markets
Generic manufacturers	Potential suppliers of cromolyn sodium products after patent and regulatory barriers declined

The supplied information does not establish a specific Paragraph IV filing, ANDA number, district-court case, settlement agreement, or licensing transaction tied specifically to U.S. Patent 4,395,421. No such event should be attributed to the patent without a verified court, FDA, or transaction record.

What patent litigation affects U.S. Patent 4,395,421?

The patent is expired, so any historical litigation would no longer create a prospective launch injunction based solely on this patent. The supplied claim text does not identify a litigation docket, asserted claims, accused products, judgment, or settlement.

For a litigation review, the material issues would have been:

Whether the accused cromolyn sodium was produced by wet granulation.
Whether its bulk density fell within the claimed range.
Whether the composition contained less than 5% other compounds.
Whether the particle-size limitations were met.
Whether the capsule-fill and moisture limitations were satisfied.
Whether the alleged use involved an allergic gastrointestinal or nasal disorder.
Whether the patent was valid over earlier cromolyn sodium granulation and formulation technology.

A product-by-process claim could also face a novelty or obviousness challenge based on an earlier product having the same physical properties, even if the earlier product was made through a different process. Under U.S. patent law, process language in a product-by-process claim does not necessarily rescue an otherwise anticipated product.[4]

How does the patent compare with current generic-entry risks?

The patent presents no current generic-entry risk because it is expired. Current risk analysis for cromolyn sodium would instead focus on:

FDA approval status by route and dosage form;
Remaining formulation or device patents, if any;
Regulatory exclusivity;
Manufacturing know-how;
Drug-master-file controls;
Supply of pharmaceutical-grade cromolyn sodium;
Device or nasal-delivery technology;
Market withdrawal or shortage issues; and
Product-specific Orange Book data.

For a conventional small-molecule cromolyn sodium product, the principal barriers are more likely to be regulatory, commercial, manufacturing, and market-size constraints than the expired claims of U.S. Patent 4,395,421.

What manufacturing and IP barriers did the patent address?

The patent’s technical problem was handling disodium cromoglycate in a dosage form. The claims indicate that the invention sought a material with:

Improved bulk handling;
Controlled density;
Reduced excessive fines;
Defined granule hardness;
High active content;
Acceptable capsule filling;
Limited excipient use; and
Controlled residual water.

These characteristics can affect powder flow, dose uniformity, encapsulation, aerosolization, dissolution, and patient administration. The patent therefore had practical manufacturing value even though it did not claim the active pharmaceutical ingredient as a chemical entity.

The remaining know-how may still have commercial value after patent expiry. Examples include granulation endpoint control, drying conditions, sieve selection, moisture specifications, capsule-filling settings, and analytical methods. Those items may be protected through trade secrets or unpatented process know-how, but they are not enforceable as patent rights under U.S. Patent 4,395,421.

What generic launch scenarios exist?

Immediate launch based on patent expiration

A manufacturer can evaluate a U.S. generic or alternative cromolyn sodium product without treating Patent 4,395,421 as an unexpired patent barrier. The product would still require the appropriate FDA approval pathway.

Design-around launch

A product could avoid the historical claim architecture by using:

A non-wet-granulated active;
A density outside the claimed range;
More than 5% non-water compound in embodiments subject to claim 1;
A different particle-size profile;
A lubricated formulation where claim 9 is relevant; or
A dosage form outside the claimed capsule or amount limitations.

Because the patent is expired, these design-around strategies are mainly relevant to historical freedom-to-operate analysis and to understanding the technical boundaries of the invention.

505(b)(2) or nontraditional product

A reformulated nasal, inhaled, oral, or device-enabled cromolyn sodium product could require a 505(b)(2) application rather than an ANDA, depending on the proposed product and reference basis. Patent risk would then be assessed against any later unexpired patents covering the delivery system, formulation, device, or method of use.

What is the geographic coverage of the patent?

U.S. Patent 4,395,421 had territorial effect only in the United States. Related foreign patent family members, if any, would require separate review. A U.S. patent does not establish protection in Europe, Canada, Japan, Australia, or other jurisdictions.

For a global launch assessment, the relevant questions are:

Whether corresponding applications were filed;
Whether foreign patents issued;
Whether those patents expired;
Whether supplementary protection or regulatory extensions applied;
Whether local formulation or use patents remained active; and
Whether local regulatory exclusivity survived patent expiry.

The supplied information does not identify the foreign family or its members.

Key Takeaways

U.S. Patent 4,395,421 covers granular disodium cromoglycate, not the cromolyn sodium molecule generally.
The central limitations are wet granulation, bulk density, purity, particle-size distribution, dosage amount, capsule fill, water content, and selected administration routes.
Claims 1-7 concern the active granular material.
Claims 8-12 concern unit dosage and capsule formulations.
Claims 13 and 14 concern oral treatment of allergic gastrointestinal disorders and intranasal treatment of allergic nasal disorders.
The patent issued July 26, 1983, and its ordinary former 17-year term ended in 2000.
The patent is expired and does not create a current U.S. launch block.
Cromolyn sodium is a small molecule, so biosimilar analysis is inapplicable.
Current commercial risk would arise from later formulation, device, manufacturing, regulatory, or product-specific patents, not from this expired patent.
The supplied record does not establish a specific Paragraph IV challenge, litigation judgment, settlement, or licensing agreement involving this patent.

FAQs

Is disodium cromoglycate the same drug as cromolyn sodium?

Yes. Disodium cromoglycate is commonly called cromolyn sodium in the United States.

Does U.S. Patent 4,395,421 cover NasalCrom?

It may have been technically relevant to a qualifying intranasal granular product, but the patent does not automatically cover every NasalCrom product. Coverage would depend on the product’s manufacturing process, density, composition, and dosage characteristics. The patent is now expired.

Could a product made by dry granulation infringe the patent?

A dry-granulated product would have a potential non-infringement position against claims expressly requiring production by wet granulation. The final product’s physical characteristics and the applicable construction of the product-by-process language would still matter in a historical analysis.

Does the patent cover cromolyn sodium inhalation products?

Only potentially, and only if the product satisfied the relevant granular, process, density, and composition limitations. The claims do not broadly cover every inhaled cromolyn sodium formulation.

Are biosimilars relevant to cromolyn sodium?

No. Cromolyn sodium is a small-molecule drug. Generic-drug pathways, including ANDA and potentially 505(b)(2), are the relevant U.S. regulatory frameworks.

References

Abbott Laboratories v. Sandoz, Inc., 566 F.3d 1282 (Fed. Cir. 2009) (en banc).
U.S. Patent and Trademark Office. (1983). U.S. Patent No. 4,395,421, Disodium cromoglycate compositions and methods. Washington, DC: U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. Silver Spring, MD: U.S. Department of Health and Human Services.
In re Thorpe, 777 F.2d 695 (Fed. Cir. 1985).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	43054/76	Oct 16, 1976

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2898377	⤷ Start Trial
Australia	508134	⤷ Start Trial
Belgium	858858	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 4,395,421