U.S. Patent 6,465,504: Deferasirox Claims, Scope, Expiration and Patent Landscape

U.S. Patent No. 6,465,504 principally protects deferasirox and a broad family of substituted 1,2,4-triazole iron chelators. Claim 5 specifically covers deferasirox, chemically known as 4-[3,5-bis(2-hydroxyphenyl)-1H-[1,2,4]triazol-1-yl]benzoic acid, including pharmaceutically acceptable salts. The patent also covers related triazole compounds, selected amide and benzyl derivatives, compositions containing those compounds, and certain positional and substitutional analogs.

The patent issued on October 15, 2002. Its ordinary 20-year patent term ran from the U.S. nonprovisional filing date and expired on December 15, 2019, subject to any applicable regulatory or pediatric extension reflected in FDA records.[1] The patent is no longer the principal barrier to U.S. generic deferasirox entry.

What drug does U.S. Patent 6,465,504 protect?

The patent protects the iron chelator deferasirox and structurally related compounds.

Item	Details
U.S. patent	6,465,504
Patent title	Substituted 1,2,4-triazoles as iron chelators
Issue date	October 15, 2002
Primary assignee	Novartis-related entities
Core active ingredient	Deferasirox
Deferasirox chemical name	4-[3,5-bis(2-hydroxyphenyl)-1H-[1,2,4]triazol-1-yl]benzoic acid
Key claim	Claim 5
Main therapeutic category	Iron chelation
FDA reference products	Exjade and Jadenu
Base patent expiration	December 15, 2019
Claim type	Compound, salt and pharmaceutical-composition claims

Deferasirox binds trivalent iron and is used to reduce chronic iron overload caused by repeated blood transfusions and non-transfusion-dependent thalassemia. FDA approved Exjade in 2005 and later approved Jadenu, a tablet and granule formulation of deferasirox, in 2015.[2][3]

What does independent claim 1 cover?

Claim 1 is a broad genus claim directed to substituted 1,2,4-triazole compounds represented by formula II.

The claim defines:

R1 and R5 as independently selected aromatic substituents;
R2 and R4 as hydrogen, acyl or aroyl groups;
R3 as an amide-containing alkyl group, substituted aryl group or substituted arylalkyl group;
R6 and R7 as independently selected amino, hydroxyalkyl, alkyl, alkoxyalkyl or related substituents; and
pharmaceutically acceptable salts of the compounds.

The claim uses extensive Markush language. A Markush claim covers a defined set of chemical alternatives grouped by structural characteristics. The practical scope is therefore much broader than deferasirox alone.

Structural core

The protected compounds share a 1,2,4-triazole ring carrying substituents at positions corresponding to the two aryl groups and the ring nitrogen. The compounds generally contain phenolic or substituted phenolic groups capable of coordinating iron.

The claim is directed to compounds rather than a particular therapeutic indication. It does not require a specific iron-overload diagnosis, dosage, route of administration or formulation.

Substituent breadth

Claim 1 permits R1 and R5 to include:

hydrogen;
halogen;
lower alkyl;
halo-lower alkyl;
lower alkoxy;
halo-lower alkoxy;
carboxyl;
carbamoyl;
substituted carbamoyl; and
nitrile.

R2 and R4 may be hydrogen or selected acyl and aroyl groups. R3 has three principal alternatives:

An amino-substituted carbonylalkyl group;
A substituted aryl group; or
An arylalkyl group bearing a secondary or tertiary amino substituent.

The claim separately defines extensive alternatives for R6 and R7, including hydroxyalkyl, aminoalkyl and hydroxyalkylamino groups.

This drafting approach captures a chemical research program rather than a single commercial molecule. It can reach compounds that differ materially from deferasirox in side-chain polarity, aromatic substitution and salt form.

How do claims 2 through 9 narrow the patent scope?

Claims 2 through 9 create progressively narrower species and composition claims.

Claim	Scope
1	Broad genus of substituted 1,2,4-triazole compounds and salts
2	Narrows R2 and R4 to hydrogen and limits R1/R5 substituent classes
3	Further limits R1/R5 to hydrogen, halogen or lower alkyl; identifies narrower R3 groups
4	Covers a defined list of named compounds
5	Specifically covers deferasirox and its pharmaceutically acceptable salts
6	Covers pharmaceutical compositions containing a claim 1 compound
7	Covers the corresponding 2-benzoic-acid positional isomer
8	Covers compositions containing deferasirox
9	Covers compositions containing any claim 4 compound

Why claim 5 matters commercially

Claim 5 is the most commercially important claim because it identifies deferasirox by name and structure. It does not depend on a particular formulation, dosage strength or therapeutic use.

A product containing deferasirox would fall within claim 5 if the claim were enforceable and unexpired, regardless of whether the product was:

a dispersible tablet;
a conventional tablet;
an oral granule;
a suspension;
a generic equivalent; or
a pharmaceutically acceptable salt of deferasirox.

Why claims 6, 8 and 9 matter

Claims 6, 8 and 9 are composition claims. They require a pharmaceutical composition containing a covered compound and a pharmaceutically acceptable carrier or diluent.

Claims 8 and 9 are narrower than claim 6 because they identify compounds from claims 4 and 5. Claim 8 is directed specifically to a composition containing deferasirox.

These claims could have supported an infringement theory against a finished medicinal product, but they expired with the patent term.

Does U.S. Patent 6,465,504 cover deferasirox specifically?

Yes. Claim 5 specifically covers deferasirox.

The compound listed in claim 5 is:

4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid

This is the active pharmaceutical ingredient marketed as deferasirox. Claim 8 separately covers a pharmaceutical composition containing deferasirox.

The patent also identifies several related compounds, including:

amide-substituted deferasirox analogs;
aminobenzyl triazole derivatives;
chloro- and fluoro-substituted phenolic analogs;
methyl-substituted phenolic analogs; and
2-benzoic-acid positional analogs.

What formulations are protected by U.S. Patent 6,465,504?

The patent protects pharmaceutical compositions containing covered compounds, but it does not claim a detailed commercial formulation architecture.

The claims do not specify:

a particular excipient;
a specific particle-size distribution;
a defined dissolution profile;
a particular tablet hardness;
a dispersible-tablet manufacturing process;
a granule formulation;
a coating system; or
a controlled-release profile.

The patent therefore provides compound-level and general composition protection. More specific protection for Exjade, Jadenu, oral granules, solid-state forms or manufacturing processes would need to arise from separate patents.

Exjade and Jadenu distinction

Exjade was initially marketed as a dispersible tablet. Jadenu was developed as a film-coated tablet and later as oral granules. The products contain the same active ingredient but have different dosage-form and administration characteristics.[2][3]

U.S. Patent 6,465,504 is not limited to Exjade's dispersible-tablet presentation. It reaches deferasirox in any pharmaceutical composition within the claim language. It also does not, by itself, establish protection for every formulation-specific feature of Jadenu.

When did U.S. Patent 6,465,504 lose exclusivity?

The base patent term expired on December 15, 2019.

The relevant exclusivity analysis is:

Exclusivity layer	Status
Compound patent, U.S. 6,465,504	Expired December 15, 2019
FDA new chemical entity exclusivity	Expired before generic entry
Product-specific formulation patents	Must be assessed separately
Pediatric exclusivity	Relevant only if granted and attached to an unexpired listed patent
Regulatory exclusivity for deferasirox	No longer a primary entry barrier

Patent expiration and FDA regulatory exclusivity are separate concepts. A drug can lose patent protection while a limited regulatory exclusivity period remains, and a patent can expire while later formulation patents remain enforceable.

For deferasirox, the key commercial transition occurred after expiration of the compound patent, when ANDA applicants could seek approval for products containing the same active ingredient, subject to any remaining listed patents and FDA requirements.

What is the Orange Book status of U.S. Patent 6,465,504?

The patent was listed in the FDA Orange Book for deferasirox reference products, including Exjade-related products. Its listing identified a compound patent relevant to deferasirox.[4]

The Orange Book listing did not convert the patent into a formulation-specific patent. It provided the regulatory mechanism through which an ANDA applicant had to address the listed patent, typically through:

a Paragraph III certification stating that the patent had not expired;
a Paragraph IV certification alleging that the patent was invalid, unenforceable or not infringed; or
a statement that the patent was not relevant to the proposed product.

After expiration, the patent no longer blocked approval on its own.

The Orange Book should be reviewed separately for patents associated with:

deferasirox tablets;
deferasirox granules;
solid-state forms;
formulation processes; and
later reference-product approvals.

Which companies challenged deferasirox patents?

A Paragraph IV challenge requires a generic applicant to certify that an Orange Book-listed patent is invalid, unenforceable or will not be infringed. The existence of an ANDA filing or generic approval does not, by itself, establish that a particular company prevailed in litigation.

Public FDA records confirm the later availability of generic deferasirox products after the compound patent's expiration. The principal competitive issue shifted from claim 5 to any remaining formulation, solid-state or regulatory protections.

The patent record alone does not establish a complete list of Paragraph IV filers or the final disposition of every related litigation matter. U.S. Patent 6,465,504 should therefore be treated as an expired compound patent rather than as an active litigation barrier.

What patent litigation affected U.S. Patent 6,465,504?

The commercial litigation risk centered on the standard ANDA framework for a listed compound patent. A generic applicant seeking approval before expiration could trigger:

a Paragraph IV notice to the patent holder;
a 45-day period for the patent holder to file suit;
a potential 30-month stay of FDA approval under the Hatch-Waxman Act; and
litigation over infringement, validity and enforceability.

Because claim 5 specifically identifies deferasirox, infringement analysis for a product containing deferasirox would have been comparatively direct. The main potential defenses would have concerned:

invalidity;
patent-term expiration;
noninfringement based on a different active ingredient;
lack of enforceability; or
a statutory safe harbor for activities reasonably related to FDA submission.

After expiration, claims 5 and 8 no longer support an infringement action based on commercial manufacture, sale or use of deferasirox.

How strong was the patent estate for deferasirox?

The compound patent was strong in product-definition terms but limited in remaining life.

Strengths

Claim 5 specifically names deferasirox.
Claim 8 separately covers pharmaceutical compositions containing deferasirox.
Claim 1 reaches a broad genus of related iron chelators.
The claims cover pharmaceutically acceptable salts.
The patent does not depend on a particular indication or dosage form.

Weaknesses

The patent term expired in 2019.
The claims do not provide detailed formulation protection.
The claims do not include a method-of-treatment claim.
The claims do not cover manufacturing steps in a dedicated process claim.
A competitor using a different iron chelator would not infringe claim 5.
Later generic entry could proceed once the patent and any applicable regulatory barriers expired.

On a historical basis, U.S. Patent 6,465,504 was a high-value compound patent. On a current basis, its exclusionary strength is zero because the enforceable term has ended.

What manufacturing and intellectual-property barriers remain?

The expired patent removes the core compound barrier, but generic manufacturers still face technical and regulatory requirements.

Relevant barriers include:

reproducible synthesis of deferasirox;
control of regioisomers and impurities;
polymorph and solid-state control;
dissolution and bioequivalence for the selected dosage form;
stability of the active ingredient;
control of residual solvents and elemental impurities;
formulation-specific patents; and
FDA approval requirements.

Deferasirox contains phenolic groups and has formulation characteristics that can affect solubility and dissolution. A generic applicant must demonstrate that its product meets the applicable FDA standards for the reference dosage form. Manufacturing know-how can therefore remain commercially relevant even when the core compound patent has expired.

How does the patent compare with later deferasirox protection?

Protection category	U.S. Patent 6,465,504	Later protection
Core deferasirox compound	Yes	Usually not necessary after expiration
Broad triazole genus	Yes	May overlap with other chemical patents
Pharmaceutically acceptable salts	Yes	May be addressed in later claims
General pharmaceutical composition	Yes	Later patents may claim narrower formulations
Exjade dispersible formulation	Not specifically detailed	Potentially covered by separate formulation rights
Jadenu tablet or granule formulation	Not specifically detailed	Requires separate product and formulation analysis
Manufacturing process	Not as a primary claim category	Separate process patents may apply
Method of treatment	Not expressly claimed	Separate use patents may exist

The most important distinction is between active-ingredient protection and product-presentation protection. U.S. Patent 6,465,504 is primarily an active-ingredient patent. It should not be used as a proxy for the entire Exjade or Jadenu patent estate.

What is the revenue exposure from expiration?

Expiration of the compound patent exposed the deferasirox franchise to generic substitution and price erosion. The affected products included Exjade and, depending on the relevant approval and listed patents, later deferasirox presentations.

Revenue exposure depends on:

U.S. sales share;
payer substitution;
generic launch timing;
the number of approved ANDA products;
formulation differences between generic and branded products;
specialty-pharmacy distribution; and
remaining formulation or regulatory exclusivity.

The commercial impact is generally greatest for the active ingredient when the principal patent is a composition-of-matter patent. Once generic deferasirox became available, a manufacturer could compete without reproducing Novartis' brand, labeling presentation or commercial packaging.

What generic launch scenarios existed after expiration?

The principal scenarios were:

Immediate post-expiration launch

Applicants with approved ANDAs and no surviving blocking patent could launch after December 15, 2019, subject to FDA approval timing and any applicable exclusivity.

Delayed launch because of formulation patents

A generic applicant could obtain approval but remain subject to a later patent covering a dosage form, solid-state form or manufacturing process.

Paragraph IV launch before expiration

An applicant could launch before the base patent expired if it prevailed in litigation, reached a settlement permitting launch, or relied on a finding that the listed patent was invalid, unenforceable or not infringed.

Limited product substitution

A generic product could enter one dosage form while remaining unable to substitute automatically for another dosage form, depending on FDA product-specific requirements and state substitution rules.

Were there licensing deals for U.S. Patent 6,465,504?

The patent and FDA records identify the Novartis-related originator position. They do not establish a material third-party license that transferred control of the core U.S. patent.

Commercial arrangements involving generic deferasirox, authorized generics or distribution agreements would need to be distinguished from ownership of U.S. Patent 6,465,504. Patent ownership, FDA sponsorship, marketing authorization and commercial distribution are separate rights.

Does biosimilar risk apply to deferasirox?

No. Deferasirox is a chemically synthesized small molecule, not a biologic. Biosimilar provisions under the Biologics Price Competition and Innovation Act do not apply.

The relevant competitive pathway is the ANDA process under section 505(j) of the Federal Food, Drug, and Cosmetic Act. Generic applicants must demonstrate pharmaceutical equivalence and bioequivalence to the applicable reference product.[5]

Key Takeaways

U.S. Patent 6,465,504 is the core U.S. compound patent for deferasirox.
Claim 5 specifically covers deferasirox and its pharmaceutically acceptable salts.
Claims 6 and 8 cover pharmaceutical compositions containing covered compounds, including deferasirox.
Claim 1 covers a broad genus of substituted 1,2,4-triazole iron chelators.
The patent does not primarily protect a particular Exjade or Jadenu formulation.
The base patent term expired on December 15, 2019.
Generic competition is governed by the ANDA pathway, not biosimilar law.
Later formulation, solid-state and manufacturing patents must be analyzed separately.
The expired patent no longer provides an enforceable barrier to commercial deferasirox manufacture or sale.

FAQs About U.S. Patent 6,465,504 and Deferasirox

Is deferasirox covered by claim 5 of U.S. Patent 6,465,504?

Yes. Claim 5 specifically identifies 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid, the chemical compound known as deferasirox.

Can a generic manufacturer make deferasirox after the patent expired?

Yes, subject to FDA approval and compliance with any separately enforceable patents covering the proposed dosage form, formulation, solid-state form or manufacturing process.

Does U.S. Patent 6,465,504 cover Jadenu?

It covers the deferasirox active ingredient in Jadenu. It does not, based on the cited claims, provide detailed protection for every tablet or granule formulation used in Jadenu.

Is U.S. Patent 6,465,504 a method-of-use patent?

No. The cited claims are directed to compounds, salts and pharmaceutical compositions. They do not expressly claim treatment of iron overload as a method.

Does the patent cover deferasirox salts?

Yes. Claims 1, 4 and 5 expressly include pharmaceutically acceptable salts within their scope.

References

United States Patent and Trademark Office. (2002). U.S. Patent No. 6,465,504, Substituted 1,2,4-triazoles as iron chelators.
U.S. Food and Drug Administration. (2005). Exjade (deferasirox) prescribing information.
U.S. Food and Drug Administration. (2015). Jadenu (deferasirox) prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application process under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	1593/96	Jun 25, 1996

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0914118	⤷ Start Trial	300248	Netherlands	⤷ Start Trial
European Patent Office	0914118	⤷ Start Trial	PA2007001	Lithuania	⤷ Start Trial
European Patent Office	0914118	⤷ Start Trial	CA 2006 00035	Denmark	⤷ Start Trial
European Patent Office	0914118	⤷ Start Trial	06C0049	France	⤷ Start Trial
European Patent Office	0914118	⤷ Start Trial	SPC 035/2006	Ireland	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,465,504