United States Patent 6,833,384: Scope, Claims, Expiration, and Patent Landscape for LAQ824

U.S. Patent No. 6,833,384 covers two specific histone deacetylase inhibitor compounds associated with Novartis’ LAQ824 program, their pharmaceutical compositions, and methods of treating proliferative disorders. The patent does not claim a broad class of all hydroxamic-acid HDAC inhibitors. Its strongest protection is directed to the named chemical compounds, while the composition and treatment claims depend on those compounds.

The patent’s principal commercial relevance was LAQ824, also known as NVP-LAQ824, the compound in claim 4. LAQ824 entered clinical development but did not obtain FDA approval. The patent’s ordinary U.S. term has expired, eliminating current blocking protection from this patent alone. No Orange Book listing or approved generic pathway is associated with LAQ824.

What compounds does U.S. Patent 6,833,384 protect?

Claims 1 and 4 protect two closely related hydroxamic-acid compounds.

Claim	Protected compound	Key structural distinction
1	N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)-ethyl]-amino]methyl]phenyl]-2E-2-propenamide, and pharmaceutically acceptable salts	2-methyl substitution on the indole ring
4	N-hydroxy-3-[4-[[[2-(1H-indol-3-yl)ethyl]-amino]methyl]phenyl]-2E-2-propenamide, and pharmaceutically acceptable salts	Unsubstituted indole ring; associated with LAQ824/NVP-LAQ824

Both compounds have the same principal pharmacophore:

A hydroxamic acid group.
A trans-cinnamamide or 2E-propenamide linker.
A para-substituted phenyl ring.
A benzylaminoethyl indole side chain.
HDAC-inhibitory activity.

The patent protects the compounds as defined chemical entities, not merely by their biological activity. A competing molecule with HDAC inhibition but a different chemical structure would not infringe claim 1 or claim 4 solely because it produces the same pharmacological effect.

What is LAQ824?

LAQ824 is generally identified as the compound in claim 4, the unsubstituted indole derivative. It is a hydroxamic-acid histone deacetylase inhibitor developed by Novartis and evaluated in oncology studies.

The claim 1 compound is a 2-methyl analog. It is structurally related but is not the same compound. A product containing only the claim 1 compound would not literally practice claim 4, and a product containing only LAQ824 would not literally practice claim 1.

How broad are the compound claims?

Claims 1 and 4 are narrow composition-of-matter claims. Each selects one specifically defined compound or a pharmaceutically acceptable salt.

The scope does not expressly extend to:

A broad Markush family of substituted indoles.
All hydroxamic-acid HDAC inhibitors.
All salts unless they qualify as pharmaceutically acceptable salts of the claimed compound.
Prodrugs or metabolites with materially different structures.
Polymorphs unless they remain the same claimed compound and are covered under applicable claim construction.
Combination products that do not contain one of the claimed compounds.

The phrase “pharmaceutically acceptable salt thereof” expands each compound claim to salt forms that retain the relevant compound identity and are suitable for pharmaceutical use. It does not ordinarily cover unrelated salt-like derivatives, covalent prodrugs, or structurally modified analogs.

What structural changes could avoid the compound claims?

Potential design-around space includes changes to:

The indole nitrogen or carbon substitution pattern.
The 2-position of the indole ring.
The ethylamine linker.
The para-benzylamine connection.
The trans-cinnamamide double bond.
The hydroxamic-acid terminus.
The stereochemical or geometric configuration of the propenamide linker.

The practical infringement analysis would depend on literal claim language, the doctrine of equivalents, prosecution history, and whether the modified molecule remains chemically equivalent to the claimed compound. A small substitution, such as the 2-methyl group distinguishing claim 1, can be material because the claims separately identify the methylated and unmethylated compounds.

What pharmaceutical compositions are protected?

Claims 2 and 5 cover pharmaceutical compositions containing a therapeutically effective amount of one of the claimed compounds and a pharmaceutically acceptable carrier.

Claim	Composition scope	Dependency
2	Composition containing the claim 1 compound or salt plus a pharmaceutically acceptable carrier	Depends on claim 1
5	Composition containing the claim 4 compound or salt plus a pharmaceutically acceptable carrier	Depends on claim 4

These claims are functional composition claims. They do not specify:

A particular tablet or capsule formulation.
A specific excipient.
A dosage strength.
A release profile.
An injectable formulation.
A nanoparticle, liposome, or other delivery system.
A particular stability profile.
A specific combination with another anticancer agent.

A finished pharmaceutical product containing LAQ824 with conventional excipients could fall within claim 5 if the product met the claim’s therapeutic-amount and carrier requirements. The patent does not appear, based on the supplied claims, to provide separate protection for a sophisticated formulation technology.

What formulation patents are relevant?

The supplied claims do not establish a separate formulation patent estate. They cover the presence of the active compound in a pharmaceutical composition, rather than a defined formulation architecture.

For diligence purposes, a later-filed patent family would need to be reviewed for:

Solid-state forms.
Crystalline polymorphs.
Salt selection.
Amorphous dispersions.
Oral bioavailability improvements.
Injectable formulations.
Sustained-release dosage forms.
Combination formulations.
Manufacturing processes that control impurity levels.

No such later patent is established by U.S. Patent 6,833,384 itself.

What methods of treatment does U.S. Patent 6,833,384 cover?

Claims 3 and 6 cover administering one of the claimed compounds to a mammal to treat a proliferative disorder.

The listed disorders include:

Breast cancer.
Genitourinary cancer.
Lung cancer.
Small-cell and non-small-cell lung cancer.
Gastrointestinal and colorectal cancer.
Prostate cancer, including hormone-refractory prostate cancer.
Renal, brain, gastric, pancreatic, ovarian, bladder, epidermoid, and head-and-neck cancers.
Melanoma.
Neuroblastoma.
Leukemias.
Fibrosis, including pulmonary and renal fibrosis.
Angiogenesis.
Psoriasis.
Atherosclerosis.
Smooth-muscle proliferation.
Stenosis and restenosis after angioplasty.
Tumors resistant to other chemotherapeutics.
Tumors affected by multidrug resistance.

The claims use a broad disease list, but the method remains limited to treatment with the specific compound recited in the relevant parent claim.

How do claims 3 and 6 differ?

Claim 3 depends on claim 1 and therefore requires the 2-methyl indole compound.

Claim 6 depends on claim 4 and therefore requires the unsubstituted indole compound, LAQ824.

The disease lists are substantially parallel. The principal distinction is the active compound.

What do claims 7 and 8 add?

Claims 7 and 8 narrow the treatment claims to specified disease categories:

Claim	Parent claim	Narrowed indications
7	Claim 3	Lung cancer or tumors, non-small-cell lung cancer or tumors, colon cancer or tumors, or fibroblasts
8	Claim 6	Lung cancer or tumors, non-small-cell lung cancer or tumors, colon cancer or tumors, or fibroblasts

Claims 7 and 8 may have been designed to emphasize experimental or commercially relevant activity against lung cancer, non-small-cell lung cancer, colon cancer, or fibroblast proliferation. They do not expand the patent beyond claims 3 and 6. They are narrower fallback claims.

The reference to “fibroblasts” is broader and less conventionally framed than the cancer indications. In infringement litigation, the meaning of treating fibroblasts would depend on the specification, prosecution record, and whether the asserted activity is treatment of a proliferative fibroblast-related condition rather than administration for an unrelated purpose.

When did U.S. Patent 6,833,384 expire?

U.S. Patent 6,833,384 was granted on December 21, 2004, according to USPTO patent records. Its term is governed primarily by the 20-year rule applicable to applications filed after June 8, 1995, subject to patent-term adjustment and any applicable patent-term extension.

The relevant priority chain and term calculation should be distinguished:

Event	Significance
Earliest claimed priority	Establishes priority for prior-art purposes
PCT or U.S. nonprovisional filing	Determines the baseline patent term under the applicable statute
U.S. grant	Determines enforceability during the remaining term but does not normally start the 20-year term
Patent-term adjustment	Can extend the term for qualifying USPTO delays
Patent-term extension	Potentially extends certain approved drug patents under 35 U.S.C. § 156

Public patent records associate the patent with Novartis and an international priority chain dating to approximately 1999. On that basis, the ordinary patent term ran to approximately 2020, subject to any patent-term adjustment. No FDA patent-term extension for an approved LAQ824 product is identified because LAQ824 was not approved.

The patent therefore should be treated as expired for ordinary U.S. patent-term purposes. A current commercial product would not ordinarily face an infringement claim based solely on this patent.

What is the FDA and Orange Book status of LAQ824?

LAQ824 has no FDA approval for an oncology indication. It is not an FDA-listed active ingredient with an approved new drug application, and it does not have an Orange Book-listed reference product.

Regulatory issue	Status
FDA approval	No approval identified
Approved indication	None
Orange Book reference listed drug	None
Approved generic	None
505(b)(2) exclusivity	None identified
Biosimilar pathway	Not applicable
Clinical development	Investigational oncology development
Commercial exclusivity	No active FDA product exclusivity

Because LAQ824 is a small molecule, a future competitor would pursue a generic or 505(b)(2) pathway rather than a biosimilar pathway. A biosimilar application under the Public Health Service Act is not the relevant regulatory route.

The lack of approval also means that patent litigation based on an ANDA Paragraph IV filing would not have developed around an Orange Book-listed LAQ824 product.

Were there Paragraph IV challenges or patent litigation?

No material U.S. Paragraph IV litigation is identified for U.S. Patent 6,833,384. The principal reason is commercial: LAQ824 did not become an approved drug with an Orange Book-listed reference product, so an ANDA applicant had no conventional Orange Book patent certification framework to trigger.

The absence of reported Paragraph IV litigation should not be confused with a finding that every possible use or follow-on product was free of patent risk. Separate patents could have covered:

Other HDAC inhibitors.
Combination treatment regimens.
Clinical biomarkers.
Formulations.
Manufacturing processes.
Other Novartis HDAC compounds.
Formulations or uses developed by third parties.

Based on the claims supplied, U.S. Patent 6,833,384 itself did not create a conventional marketed-product litigation pathway.

How does this patent compare with competing HDAC inhibitor patents?

U.S. Patent 6,833,384 occupied a narrow position within the broader HDAC inhibitor landscape.

Drug or program	Company or originator	HDAC class	Commercial status	Patent position
LAQ824 / NVP-LAQ824	Novartis	Hydroxamic-acid pan-HDAC inhibitor	Not approved	Covered by compound and use claims in U.S. 6,833,384
Vorinostat / SAHA	Merck, originally development associated with Aton Pharma	Hydroxamic-acid HDAC inhibitor	FDA approved	Separate composition-of-matter and use patent estate
Belinostat	TopoTarget/Spectrum	Hydroxamic-acid HDAC inhibitor	FDA approved	Separate patents and regulatory exclusivity history
Panobinostat	Novartis	Hydroxamic-acid pan-HDAC inhibitor	FDA approved	Separate Novartis patent estate
Romidepsin	Gloucester Pharmaceuticals, later Celgene/Bristol Myers Squibb	Cyclic peptide HDAC inhibitor	FDA approved	Chemically unrelated patent estate
Chidamide	Chipscreen	Benzamide HDAC inhibitor	Approved in certain jurisdictions	Different chemical and geographic estate

LAQ824 is chemically closer to vorinostat, belinostat, and panobinostat than to romidepsin. Chemical similarity does not by itself establish patent overlap. Each product’s infringement position depends on the specific claims in the relevant patent families.

How strong is the patent estate?

The estate was strong in one dimension and limited in another.

Strong points included:

Specific composition-of-matter claims.
Coverage of pharmaceutically acceptable salts.
Parallel composition claims.
Broad treatment claims covering multiple cancers and proliferative disorders.
Dependent claims directed to non-small-cell lung cancer, colon cancer, and fibroblast-related activity.

Limitations included:

No broad claim to all HDAC inhibitors.
No explicit formulation architecture in the supplied claims.
No explicit combination-treatment claim.
No approved product supporting regulatory exclusivity.
Patent expiration approximately two decades after the priority-era filing.
No continuing commercial value after expiration absent a separate unexpired patent family.

The strongest period of exclusivity was therefore the period before expiration, when a structurally identical LAQ824 product could have faced composition-of-matter and method-of-use claims.

What generic entry risks exist?

For the original patent, current generic-entry risk is low because the patent term has expired and LAQ824 lacks an approved reference product.

Historical risks would have included:

Direct manufacture or sale of the claim 4 compound.
Sale of a pharmaceutically acceptable salt of LAQ824.
Sale of a pharmaceutical composition containing LAQ824.
Use of LAQ824 to treat a listed proliferative disorder.
Use in non-small-cell lung cancer, colon cancer, or fibroblast-related indications under claim 8.

A competitor using a structurally different HDAC inhibitor would face a separate analysis under other patents. A competitor developing a new analog could avoid literal infringement of claims 1 and 4 but would need to assess equivalents, later patent families, and regulatory exclusivity.

What geographic coverage does the patent provide?

U.S. Patent 6,833,384 provides protection only in the United States. Foreign protection would depend on corresponding national patents from the relevant international application.

A global freedom-to-operate review would require separate checks in:

European Patent Office member states.
Japan.
China.
Canada.
Australia.
South Korea.
Switzerland.
Major oncology markets in Latin America.

Patent expiration dates could differ because of:

National filing dates.
Patent-term adjustment or supplementary protection certificates.
Local prosecution delays.
Continuation or divisional applications.
Foreign claim amendments.
Country-specific maintenance failures.

The U.S. expiration of this patent does not establish that every corresponding foreign patent has expired.

What manufacturing and intellectual-property barriers remain?

The compound claims can create manufacturing risk even where the final product is not marketed. Potentially relevant activities include:

Synthesis of the exact claimed active ingredient.
Production of a pharmaceutically acceptable salt.
Sale to a clinical sponsor.
Importation into the United States.
Contract manufacturing for clinical trials.
Use in a U.S. research or treatment program.

After expiration, this specific patent no longer provides an ordinary U.S. manufacturing barrier. Separate process patents, impurity-control patents, polymorph patents, or later formulation patents could still affect commercialization. The supplied claims do not establish those additional barriers.

Key Takeaways

U.S. Patent 6,833,384 covers two specific hydroxamic-acid HDAC inhibitors.
Claim 4 covers LAQ824/NVP-LAQ824, the unsubstituted indole compound.
Claim 1 covers the related 2-methyl indole analog.
Claims 2 and 5 cover pharmaceutical compositions containing the respective compounds.
Claims 3 and 6 cover treatment of broad proliferative disorders.
Claims 7 and 8 narrow treatment to lung cancer, non-small-cell lung cancer, colon cancer, and fibroblast-related conditions.
The patent does not claim all HDAC inhibitors or a broad genus of hydroxamic-acid compounds.
LAQ824 was not FDA approved and has no Orange Book-listed reference product.
No material Paragraph IV litigation is associated with this patent.
The ordinary U.S. patent term expired approximately in 2020, subject to the recorded patent-term calculation.
Current commercial risk depends mainly on later patents, foreign counterparts, process patents, and any new formulation or use claims.

FAQs About U.S. Patent 6,833,384 and LAQ824

Is LAQ824 still patent protected in the United States?

U.S. Patent 6,833,384 is no longer within its ordinary enforceable term. Any current U.S. risk would need to arise from a different unexpired patent.

Does U.S. Patent 6,833,384 cover panobinostat?

No. Panobinostat is a separate HDAC inhibitor with a different chemical structure and separate patent estate.

Can a company develop a generic LAQ824 product?

There is no approved LAQ824 reference product for a conventional ANDA pathway. A sponsor would need to evaluate the appropriate FDA regulatory route and any later patents before development.

Does the patent cover LAQ824 combinations with chemotherapy?

The supplied claims do not expressly recite a combination with another anticancer agent. A combination may still require analysis under separate patents or under infringement theories based on the claimed composition or method.

Does patent expiration eliminate all LAQ824 development risk?

No. Expiration of U.S. Patent 6,833,384 eliminates the blocking effect of that patent, but later patents, foreign rights, manufacturing patents, regulatory requirements, and clinical-development obligations may remain relevant.

References

Novartis AG. (2004). U.S. Patent No. 6,833,384: Hydroxamic acid derivatives and pharmaceutical compositions and methods of use thereof. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
United States Code. (2024). 35 U.S.C. §§ 154, 156, and 271. United States Government Publishing Office.
National Library of Medicine. (2024). ClinicalTrials.gov records for LAQ824 and NVP-LAQ824. U.S. National Library of Medicine.
Marks, P. A., & Xu, W. S. (2009). Histone deacetylase inhibitors: Potential in cancer therapy. Journal of Cellular Biochemistry, 107(4), 600-608.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1318980	⤷ Start Trial	CA 2015 00068	Denmark	⤷ Start Trial
European Patent Office	1318980	⤷ Start Trial	92890	Luxembourg	⤷ Start Trial
European Patent Office	1318980	⤷ Start Trial	15C0086	France	⤷ Start Trial
European Patent Office	1318980	⤷ Start Trial	300778	Netherlands	⤷ Start Trial
European Patent Office	1318980	⤷ Start Trial	1590070-7	Sweden	⤷ Start Trial
European Patent Office	1318980	⤷ Start Trial	122015000098	Germany	⤷ Start Trial
European Patent Office	1318980	⤷ Start Trial	CR 2015 00068	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,833,384

Summary for Patent: 6,833,384