US Patent 5,110,806: Scope, Claim Construction, Expiration, and Synthetic Lung Surfactant Patent Landscape

US Patent 5,110,806 covers synthetic lung surfactant compositions built around dipalmitoyl phosphatidylcholine, or DPPC, a C14-C18 fatty alcohol, and a nonionic surfactant. The narrowest and commercially most relevant embodiment uses DPPC, hexadecanol, and tyloxapol in defined percentage ranges, including a powdered lyophilized formulation.

The patent issued in 1992 and is expired. Its claims no longer create an enforceable U.S. exclusion right, but they remain relevant for freedom-to-operate analysis, patent-history reviews, formulation benchmarking, and assessment of later surfactant patents.

What does US Patent 5,110,806 protect?

The patent protects composition, formulation, and improvement claims directed to a three-component artificial lung surfactant:

DPPC as the principal phospholipid.
A C14-C18 fatty alcohol, particularly hexadecanol.
A nonionic, physiologically acceptable surface-active or dispersing agent, particularly tyloxapol.

The patent's central technical proposition is that adding a minor amount of a nonionic surfactant to a DPPC-fatty alcohol system improves dispersion in aqueous suspension. The claimed compositions are intended for pulmonary surfactant replacement, particularly in premature infants with respiratory distress syndrome.

The claims are composition-focused. They do not expressly claim a method of treating a patient, a dosing regimen, a delivery device, or a manufacturing process.

Core patent information

Item	Information
U.S. patent	US 5,110,806
Title	Synthetic lung surfactant compositions
Issue date	May 5, 1992
Principal active phospholipid	Dipalmitoyl phosphatidylcholine, also called DPPC or pulmonary surfactant phosphatidylcholine
Fatty alcohol	C14-C18 fatty alcohol; hexadecanol in several claims
Surfactant	Nonionic physiologically acceptable surface-active agent; tyloxapol in dependent and narrow claims
Dosage forms	Aqueous suspension and powdered lyophilized composition
U.S. term	Expired
Key commercial association	Synthetic surfactant technology associated with Exosurf-type formulations

How do the claims divide into technical categories?

The 17 claims fall into four main groups.

Broad composition claims: claims 1, 2 and 6

Claims 1, 2 and 6 cover synthetic lung surfactant compositions containing DPPC, a C14-C18 fatty alcohol, and a nonionic surface-active agent.

Claim 1 narrows the fatty alcohol to hexadecanol.

Claim 2 narrows the surface-active agent to tyloxapol.

Claim 6 uses broader functional language, covering a nonionic physiologically non-toxic dispersing surface-active agent.

These claims require DPPC to be at least 80% by weight of the combined DPPC-plus-fatty-alcohol fraction. That calculation is important. The claim does not require DPPC to be 80% of the entire formulation after the surfactant is included.

For example, a composition containing:

80 parts DPPC,
20 parts hexadecanol, and
10 parts tyloxapol,

would satisfy the DPPC-to-fatty-alcohol ratio because DPPC represents 80% of the DPPC-plus-hexadecanol subtotal. DPPC would represent approximately 72.7% of the total organic components.

Improvement claims: claims 3, 5 and 9

Claims 3 and 9 are written as improvement claims. They assume an artificial lung surfactant containing DPPC and a C14-C18 fatty alcohol, then add a third component: a nonionic physiologically non-toxic surface-active agent.

Claim 3 narrows that agent to an alkyl aryl polyether alcohol.

Claim 5 further narrows claim 3 to tyloxapol.

Claim 9 retains broader dispersing-agent language without specifying tyloxapol.

The improvement claims focus on enhanced dispersion rather than a specific medical outcome. In an infringement analysis, the accused formulation would need to satisfy the underlying DPPC-fatty alcohol structure and contain the claimed third component.

Powdered and lyophilized formulations: claims 4, 10 and 15-17

Claims 4, 10 and 15-17 cover dry or lyophilized formulations.

Claim 4 is relatively narrow because it requires:

DPPC;
a C14-C18 fatty alcohol;
hexadecanol specifically; and
tyloxapol specifically.

Claim 10 is broader because it does not require hexadecanol or tyloxapol by name.

Claims 15-17 add the patent's most specific composition limitations, including the alkyl aryl polyether alcohol structure and percentage ranges for the fatty alcohol and surfactant.

These claims are directed to a dry product that can be reconstituted before administration. The lyophilization limitation can materially narrow infringement exposure compared with claims covering any synthetic surfactant suspension.

Optimized percentage claims: claims 11-14

Claims 11-14 are the most technically defined claims.

Claim 11 requires:

DPPC at least 80% of the combined DPPC and fatty alcohol;
fatty alcohol at approximately 7%-10% of the organic components; and
nonionic alkyl aryl polyether alcohol at approximately 6%-11% of the organic components.

Claim 12 specifies tyloxapol.

Claim 13 raises the DPPC requirement to at least 90% of the DPPC-plus-fatty-alcohol subtotal.

Claim 14 combines the 90% DPPC threshold with tyloxapol.

Claims 11-14 are narrower but potentially stronger against a formulation that uses the specific Exosurf-type ratio.

What are the key claim-construction issues?

How is the 80% DPPC limitation calculated?

The claims use two different percentage bases.

The first is:

DPPC is at least 80% of the combined weight of DPPC and fatty alcohol.

The second, used in claims 11 and 15, is:

fatty alcohol and surfactant percentages are calculated against the total organic components.

Those denominators are not interchangeable.

Let:

D = DPPC;
F = fatty alcohol; and
S = surface-active agent.

The broad ratio is:

D / (D + F) >= 80%

The narrow formulation ranges are calculated as:

F / (D + F + S) = approximately 7%-10%

and:

S / (D + F + S) = approximately 6%-11%

A formulation can therefore contain less than 80% DPPC of the total organic mixture while still meeting the 80% DPPC-to-fatty-alcohol limitation.

What does "consisting essentially of" permit?

The phrase "consisting essentially of" generally permits additional ingredients that do not materially affect the basic and novel characteristics of the claimed composition. The patent identifies the DPPC-fatty alcohol-surfactant combination and improved dispersion as those central characteristics.

This language is narrower than "comprising" but broader than "consisting of." Saline, water, buffers, stabilizers, cryoprotectants and packaging-related materials may not automatically avoid the claims if they do not materially alter the claimed surfactant system. Conversely, an additional lipid, protein, polymer or active ingredient that materially changes dispersion, surface activity or pulmonary performance could create a substantial claim-construction issue.

Does a competitor need to use tyloxapol?

No. The broad claims cover a class of nonionic physiologically acceptable surface-active or dispersing agents. Tyloxapol is required only by selected dependent claims and narrower embodiments.

A formulation using another nonionic surfactant could fall within claims 3, 6, 9, 10, 11 or 15 if the other claim limitations are met. The critical questions would be whether the material is nonionic, physiologically acceptable, non-toxic, and within the claimed structural or functional category.

What formulations are specifically protected?

The most commercially recognizable claimed formulation is an Exosurf-type composition containing DPPC, hexadecanol and tyloxapol.

Claim coverage by formulation type

Formulation characteristic	Relevant claims
DPPC plus C14-C18 fatty alcohol plus nonionic surfactant	6, 9, 10
Hexadecanol as fatty alcohol	1, 4, 7
Tyloxapol as surfactant	2, 5, 12, 14, 17
Aqueous saline suspension	8
Powdered or lyophilized formulation	4, 10, 15-17
Alkyl aryl polyether alcohol surfactant	3, 11, 15
Fatty alcohol at about 7%-10% of organic components	11, 15
Surfactant at about 6%-11% of organic components	11, 15
DPPC at least 90% of DPPC-plus-fatty-alcohol subtotal	13, 14, 16

The patent does not require a particular particle size, vial configuration, aerosol device, intratracheal catheter or administration volume.

When did US Patent 5,110,806 lose exclusivity?

US Patent 5,110,806 expired in 2009 based on the pre-1995 U.S. patent-term rule, which generally provided 17 years from issue for patents of this type. With an issue date of May 5, 1992, the ordinary term ended on May 5, 2009, absent a term extension or other unusual adjustment.

The patent therefore presents no current U.S. patent-barrier risk. A current product cannot infringe an expired patent, although the patent may remain relevant to:

prior-art analysis;
obviousness evaluations;
patent prosecution;
formulation design history;
ownership and licensing diligence; and
comparison with later synthetic surfactant patents.

Exclusivity timeline

Event	Date or status
Patent issued	May 5, 1992
Regulatory period for the associated commercial product	Separate from patent term
Patent expiration	2009
Current enforceability	Expired
Current Paragraph IV relevance	None for this expired patent
Current Orange Book patent-blocking effect	None

What was the FDA status of the associated synthetic surfactant?

The claimed formulation is associated with Exosurf, a synthetic pulmonary surfactant developed for neonatal respiratory distress syndrome. Exosurf used a synthetic phospholipid-based system rather than an animal-derived surfactant. FDA approval and patent enforceability were separate legal events.

Exosurf's market history does not restore patent rights after expiration. A product may be discontinued, withdrawn, or commercially displaced while its patents remain enforceable, and the reverse is also true. Here, the patent has expired regardless of the product's commercial status.

The FDA later approved animal-derived surfactants such as Survanta, Curosurf and Infasurf, and approved the synthetic surfactant lucinactant, marketed as Surfaxin. Those products use different formulation approaches and are not automatically covered by US 5,110,806.

What is the Orange Book status of US Patent 5,110,806?

US 5,110,806 should not be treated as a current Orange Book barrier. Its 2009 expiration eliminates its ability to block an ANDA or another FDA approval pathway today.

Orange Book listing status must be distinguished from patent existence:

An issued patent can exist without being listed for a drug.
A listed patent can expire.
An NDA product can be discontinued while its patent records remain visible.
A formulation patent may not cover every presentation or approved use of a product.

For current regulatory diligence, the relevant question is not whether the patent appears in historical product records, but whether it has an unexpired term. For US 5,110,806, the answer is no.

Were there Paragraph IV challenges or generic litigation?

No current Paragraph IV exposure arises from US 5,110,806 because the patent expired in 2009.

Paragraph IV litigation would have been relevant only while an unexpired listed patent could block FDA approval. The patent's expiration removes the principal statutory incentive to litigate around it. Any later dispute involving a synthetic lung surfactant would more likely concern:

a later formulation patent;
a process patent;
a delivery system;
a new indication;
a device combination;
regulatory exclusivity; or
trade secrets and manufacturing know-how.

No current generic launch requires a challenge to this patent.

How does this patent compare with competing lung-surfactant estates?

US 5,110,806 is narrow relative to the broader commercial field because it depends on a particular synthetic architecture: DPPC, a C14-C18 fatty alcohol and a nonionic dispersant.

Comparative landscape

Product or technology	General composition	Relationship to US 5,110,806
Exosurf-type synthetic surfactant	DPPC, hexadecanol, tyloxapol	Closest commercial association
Survanta	Modified bovine lung surfactant	Different, animal-derived composition
Curosurf	Porcine lung surfactant	Different, animal-derived composition
Infasurf	Calf lung surfactant	Different, animal-derived composition
Lucinactant/Surfaxin	Synthetic peptide-containing surfactant system	Later and materially different synthetic approach
Generic DPPC formulations	May use DPPC with other excipients	Exposure depends on fatty alcohol, surfactant and ratio limitations

Animal-derived products generally fall outside the literal composition of the patent because they contain lung-derived proteins and lipids rather than the claimed synthetic three-component system. A later synthetic product can also avoid the patent by omitting the C14-C18 fatty alcohol, using a different dispersant architecture, or using a protein or peptide component that materially changes the composition.

How strong is the patent estate?

The historical patent estate was strongest against an exact or near-exact Exosurf-type formulation containing:

DPPC;
hexadecanol;
tyloxapol;
the claimed DPPC/fatty-alcohol ratio; and
a powder or lyophilized presentation.

Its breadth was reduced by several limitations:

The claims require DPPC and a C14-C18 fatty alcohol.
Several claims require a nonionic surfactant.
Selected claims require tyloxapol.
Claims 11-17 include narrow percentage ranges.
The patent does not broadly cover all pulmonary surfactants.
The patent does not claim animal-derived surfactants.
The patent does not claim all DPPC formulations.
The patent does not claim all methods of treating respiratory distress syndrome.

The estate's present legal strength is zero because the patent is expired. Its technical value remains moderate as a formulation disclosure and prior-art reference.

What manufacturing and intellectual-property barriers remain?

Even after patent expiration, commercial entry can require control of non-patent assets.

Manufacturing barriers

Relevant manufacturing issues include:

pharmaceutical-grade DPPC purity;
control of oxidation and hydrolysis;
reproducible incorporation of hexadecanol;
uniform tyloxapol distribution;
sterile processing;
lyophilization-cycle development;
reconstitution time;
suspension stability;
pulmonary tolerability; and
container-closure performance.

These factors can create regulatory and commercial barriers without creating patent exclusivity.

Later patent risks

A current developer should separately review later patents covering:

synthetic peptide surfactants;
recombinant surfactant proteins;
aerosolized pulmonary surfactants;
nebulizer and intratracheal delivery systems;
lyophilized surfactant cakes;
particle engineering;
combination products;
neonatal dosing protocols; and
manufacturing processes.

Those rights are distinct from US 5,110,806 and cannot be inferred from its claims.

What generic launch scenarios exist?

Because US 5,110,806 is expired, three practical entry scenarios exist.

Exact-formulation entry

A company could develop a DPPC-hexadecanol-tyloxapol formulation without infringing this expired patent. Regulatory approval would still require current FDA evidence appropriate to the product and pathway.

Design-around entry

A company could use:

a different fatty alcohol;
a different nonionic dispersant;
a peptide or protein component;
a different ratio;
a different dosage form; or
an alternative delivery technology.

These approaches could reduce exposure to later patents, although they may increase development and clinical risk.

Competing-product entry

A developer could enter with an animal-derived or peptide-containing surfactant that does not practice the claimed synthetic composition. This is the approach reflected by the broader pulmonary-surfactant market.

Key Takeaways

US 5,110,806 covers synthetic lung surfactants based on DPPC, a C14-C18 fatty alcohol and a nonionic dispersing agent.
Hexadecanol and tyloxapol are the key narrow species.
Claims 11-17 add percentage ranges and lyophilized-powder limitations.
The 80% DPPC limitation is calculated against DPPC plus fatty alcohol, not necessarily total organic ingredients.
The patent issued on May 5, 1992 and expired in 2009.
It creates no current U.S. patent-exclusivity barrier and no current Paragraph IV risk.
Exosurf-type formulations are the closest commercial embodiment.
Animal-derived products and later peptide-containing synthetic surfactants generally use materially different composition strategies.
Current diligence should focus on later formulation, delivery, manufacturing and combination-product patents.

FAQs

Is US Patent 5,110,806 still enforceable?

No. The patent expired in 2009 under the applicable pre-1995 patent-term framework.

Does a DPPC formulation infringe the patent automatically?

No. DPPC alone is insufficient. The relevant claims also require a C14-C18 fatty alcohol and a qualifying nonionic surface-active or dispersing agent, together with the applicable compositional limitations.

Does tyloxapol have to be present?

No. Tyloxapol is required only for selected claims. Broader claims cover qualifying nonionic surface-active agents without naming tyloxapol.

Can an animal-derived pulmonary surfactant fall within this patent?

Generally, no. The claims are directed to synthetic compositions centered on DPPC, fatty alcohol and nonionic surfactant components. An animal-derived product would require a separate analysis of its actual formulation and claim construction.

Does the patent cover nebulizers or intratracheal administration devices?

No. The claims provided cover compositions and powdered or lyophilized formulations. They do not expressly claim a nebulizer, catheter, dosing method or administration device.

References

U.S. Patent No. 5,110,806. (1992). Synthetic lung surfactant compositions. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
U.S. Food and Drug Administration. (n.d.). Surfactant replacement therapies and approved pulmonary surfactant products. FDA regulatory and product information.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Mexico	9203533	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,110,806