Details for Patent: 7,419,983

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Which drugs does patent 7,419,983 protect, and when does it expire?

Patent 7,419,983 protects ORIAHNN (COPACKAGED) and ORILISSA and is included in two NDAs.

This patent has thirty patent family members in twenty-three countries.

Summary for Patent: 7,419,983

Title:	Gonadotropin-releasing hormone receptor antagonists and methods related thereto
Abstract:	GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
Inventor(s):	Zhiqiang Guo, Yongsheng Chen, Dongpei Wu, Chen Chen, Warren Wade, Wesley J. Dwight, Charles Q. Huang, Fabio C. Tucci
Assignee:	Neurocrine Biosciences Inc
Application Number:	US11/627,204
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,419,983
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 7,419,983: Elagolix Compound Scope, Patent Claims, Exclusivity and Generic Risk

US Patent 7,419,983 protects the elagolix chemical class, including the sodium and calcium salts of elagolix, pharmaceutical compositions containing those compounds, and treatment of prostate cancer, benign prostatic hypertrophy, breast cancer and endometriosis. The patent is a core composition-of-matter patent for elagolix, marketed by AbbVie as Orilissa and, in combination products, as Oriahnn. The claims are materially broader than the marketed sodium salt because independent claim 1 covers a substituted pyrimidinedione genus defined by variable substituents and a C1-C6 alkanediyl linker. Claims 12-20 narrow the genus to two named chemical entities, including elagolix.

What drug does US Patent 7,419,983 protect?

US Patent 7,419,983 protects elagolix and closely related substituted pyrimidinedione gonadotropin-releasing hormone, or GnRH, antagonists.

The principal marketed compound is elagolix sodium, chemically identified as:

3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methylpyrimidine-2,4(1H,3H)-dione sodium salt.

Elagolix is a nonpeptide, orally active GnRH receptor antagonist. Orilissa was approved by the FDA in 2018 for moderate-to-severe pain associated with endometriosis. Oriahnn, approved in 2020, contains elagolix in combination with estradiol and norethindrone acetate for heavy menstrual bleeding associated with uterine fibroids.[2,3]

The patent claims are directed to the chemical substance and its use rather than to a particular tablet, capsule, dose, manufacturing process or combination regimen.

What are the independent claims in US 7,419,983?

The patent has three principal claim categories:

Claim category	Claims	Protected subject matter
Compound claims	1-20	Substituted pyrimidinediones, stereoisomers and pharmaceutically acceptable salts
Composition claims	21-30	Pharmaceutical compositions containing the claimed compound
Method-of-treatment claims	31-40	Treatment of prostate cancer, benign prostatic hypertrophy, breast cancer or endometriosis

Claims 1, 21 and 31 are the principal independent claims. The remaining claims narrow those categories through positional limitations, substituent selections, named compounds and salt forms.

Claim 1 is the broad chemical genus. Claim 21 incorporates substantially the same chemical definition into a pharmaceutical composition. Claim 31 incorporates it into a method of treatment.

How broad is claim 1?

Claim 1 covers a compound having a substituted pyrimidine-2,4-dione core with the following mandatory features:

Structural element	Claim limitation
Pyrimidinedione core	1,3-disubstituted 2,4-pyrimidinedione framework
R1a	Halogen
R1b	Alkoxy
R1c	Hydrogen
R2a	Halogen
R2b	Trifluoromethyl
R3	Methyl
R4	Phenyl
R5	Hydrogen
R6	Carboxylic acid, -COOH
X	C1-C6 alkanediyl
Stereochemistry	Stereoisomers are included
Salt coverage	Pharmaceutically acceptable salts are included

The claim therefore covers a family of analogs rather than only elagolix sodium. The main variables are:

1. The halogen on the first aryl ring.
2. The alkoxy group on that ring.
3. The halogen on the second aryl ring.
4. The length of the alkanediyl linker.
5. The pharmaceutically acceptable salt.
6. The stereochemical form.

The claim does not require the 2-fluoro-3-methoxy substitution pattern or the 2-fluoro-6-trifluoromethyl pattern that characterizes elagolix. Those restrictions appear in dependent claims.

What compounds are specifically covered by claims 12 through 20?

Claims 12-20 identify two principal chemical entities:

1. The 2-fluoro-3-methoxyphenyl analog.
2. The 2-chloro-3-methoxyphenyl analog.

The elagolix embodiment is the first compound:

3-[2(R)-{hydroxycarbonylpropyl-amino}-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methylpyrimidine-2,4(1H,3H)-dione.

The claim hierarchy is:

Claims	Scope
12	Two named compounds and their pharmaceutically acceptable salts
13	Fluoro-methoxy analog
14	Sodium or calcium salt of the fluoro-methoxy analog
15	Sodium salt, corresponding to elagolix sodium
16	Calcium salt of the fluoro-methoxy analog
17	Chloro-methoxy analog
18	Sodium or calcium salt of the chloro-methoxy analog
19	Sodium salt of the chloro-methoxy analog
20	Calcium salt of the chloro-methoxy analog

Claim 15 is the narrowest and most commercially relevant claim for Orilissa because it expressly covers elagolix sodium.

What do the composition claims protect?

Claims 21-30 cover a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound within the claim 1 genus.

These claims are narrower than a pure compound claim in one respect because they require a composition. They are broader in another respect because they can reach different dosage forms containing the claimed active ingredient, including tablets, capsules, oral solutions, suspensions and other pharmaceutical presentations if the composition contains the claimed compound.

The composition claims do not require:

• A specific excipient;
• A specific dosage strength;
• A specific release profile;
• A particular tablet coating;
• A specific manufacturing process; or
• A particular indication.

Claims 23-30 narrow the compositions to the fluoro-methoxy and chloro-methoxy compounds and their sodium and calcium salts.

What do the method-of-use claims protect?

Claims 31-40 cover administration of the claimed compounds for:

• Prostate cancer;
• Benign prostatic hypertrophy;
• Breast cancer; and
• Endometriosis.

The endometriosis indication is the commercial center of gravity for elagolix. The claim language does not expressly require a specific dose, treatment duration, route of administration or degree of symptom severity. A method may fall within the literal scope if it administers a covered compound in a pharmaceutical composition to treat one of the listed conditions.

The method claims do not expressly cover uterine fibroids. Oriahnn's fibroid indication is supported by later regulatory and patent activity involving elagolix combination therapy and dosing regimens.

How does claim dependency affect infringement analysis?

The claims form a progressive narrowing structure:

Claim 1
  -> positional limitations in claims 2-11
  -> named compounds in claim 12
  -> fluoro-methoxy compound in claim 13
  -> sodium or calcium salt in claim 14
  -> elagolix sodium in claim 15
  -> elagolix calcium in claim 16

Claim 21
  -> composition claims 22-30

Claim 31
  -> treatment claims 32-40

A generic product containing elagolix sodium would face the strongest literal read on claims 15, 21-26 and potentially 31-36, depending on the proposed indication and labeling. A product containing a different salt could still implicate claim 13 or claim 14, and the broader genus claim may apply if the salt qualifies as pharmaceutically acceptable.

A product using a different stereoisomer may remain within the claim because claim 1 expressly includes stereoisomers. A different linker length may avoid the narrow named-compound claims but could remain within claim 1 if the resulting structure satisfies the C1-C6 alkanediyl limitation.

What is the patent expiration date for US 7,419,983?

The patent issued on September 2, 2008. Its term is governed by the 20-year patent term applicable to applications filed after June 8, 1995, measured from the earliest effective nonprovisional priority date, subject to patent-term adjustment and any applicable extension.

The patent claims priority to a December 20, 2002 filing date. On a basic term calculation, the base expiration date is December 20, 2022. The operative expiration date must account for any patent-term adjustment shown in the USPTO patent record.

The patent was not the only relevant exclusivity barrier for elagolix. Later patents covering dosing, treatment regimens, combinations and other product attributes extended commercial protection beyond the basic composition-of-matter term.

Protection category	Relevance to elagolix
US 7,419,983	Core compound and salt claims
Later elagolix patents	Dosing, treatment methods, combination products and related product protection
FDA new chemical entity exclusivity	Five years from the 2018 Orilissa approval
Oriahnn regulatory exclusivity	Separate approval and combination-product protection

Patent expiration and FDA exclusivity are separate legal concepts. Expiration of US 7,419,983 did not automatically eliminate later patent barriers or prevent enforcement of unexpired method or formulation claims.

What is the Orange Book status of elagolix?

Orilissa is an FDA-approved prescription drug containing elagolix sodium. The FDA Orange Book identifies patents submitted by the NDA holder for approved products where the patents meet the listing requirements under the Hatch-Waxman framework.[4]

The commercial patent estate for elagolix has included multiple categories:

• Composition-of-matter protection;
• Treatment of endometriosis;
• Dose and dosing-regimen protection;
• Combination therapy with estrogen and progestin;
• Formulation and pharmaceutical composition protection; and
• Product-specific protection for Oriahnn.

US 7,419,983 is the foundational patent because its claims reach the active pharmaceutical ingredient itself. A later patent may be more difficult to design around for a specific product presentation, but it cannot substitute for the commercial breadth of a valid composition-of-matter claim.

Which patents protect Orilissa and Oriahnn beyond US 7,419,983?

The later patent landscape includes patents directed to clinical use and product implementation. Public FDA and patent records associate elagolix products with patents covering treatment methods and dosing concepts beyond the original compound patent.[3,4]

The relevant categories are:

Elagolix monotherapy

Orilissa uses elagolix sodium in dose-dependent regimens for endometriosis-associated pain. Later patents may cover dose selection, treatment duration, patient populations and safety-oriented dosing limitations.

Elagolix combination therapy

Oriahnn combines elagolix with estradiol and norethindrone acetate. Combination patents can cover:

• Elagolix plus estrogen;
• Elagolix plus progestin;
• Specific estrogen and progestin quantities;
• Treatment of heavy menstrual bleeding associated with uterine fibroids; and
• Regimens designed to reduce hypoestrogenic adverse effects.

Formulation protection

The original patent claims pharmaceutical compositions broadly, but they do not recite a detailed excipient system, tablet architecture or controlled-release technology. Any later formulation patent would be more narrow and would require proof that a competing product practices the specific formulation limitations.

What formulation patents are relevant to a generic elagolix product?

US 7,419,983 presents limited formulation specificity. Claims 21-30 require only a pharmaceutically acceptable carrier or diluent. That language can cover conventional oral dosage forms but does not establish protection for every particular tablet formulation.

A generic applicant may therefore face two different questions:

1. Whether the active ingredient is covered by an unexpired composition claim.
2. Whether the proposed dosage form practices a separate formulation or composition patent.

The first question is usually dispositive while the compound patent remains unexpired. After compound-patent expiration, formulation claims become more important. A generic developer could pursue a different excipient system, coating, particle size, salt, polymorph or manufacturing process, but each design-around must be evaluated against the full patent family and the approved product's listed patents.

What manufacturing and intellectual-property barriers exist?

The compound contains several technically demanding structural elements:

• A chiral amino acid-derived side chain;
• A substituted pyrimidinedione core;
• Two highly substituted aryl groups;
• A fluorinated benzyl substituent;
• A trifluoromethyl group;
• A carboxylic acid capable of salt formation; and
• A defined R stereochemical configuration.

The patent claims do not themselves require a particular synthetic route. A competitor may use an independent process without avoiding the compound claims if the final product falls within the claimed structure.

Manufacturing risks include:

Risk	Patent significance
Chiral purity	May affect whether the product is the claimed stereoisomer or a covered stereoisomer
Salt selection	Sodium, calcium and other pharmaceutically acceptable salts may remain covered
Process choice	A different process does not avoid a product claim
Intermediate patents	Later patents may cover intermediates or process steps
Solid-state form	Separate polymorph or crystalline-form claims may apply
Impurity profile	Regulatory comparability may create development cost even without direct patent infringement

For a generic applicant, the principal technical design-around is not simply a new synthesis. It is a product that does not contain the claimed active structure or does not practice additional unexpired formulation or method claims.

What Paragraph IV challenges and generic-entry risks apply?

A generic applicant seeking approval before expiration of a listed patent may submit a Paragraph IV certification alleging that the patent is invalid, unenforceable or not infringed. The relevant litigation risk depends on the patent list at the time of ANDA filing and the specific proposed label.

Potential Paragraph IV positions against US 7,419,983 could include:

• Lack of written description for the full genus;
• Lack of enablement across the C1-C6 alkanediyl range and substituent combinations;
• Obviousness based on known GnRH antagonist scaffolds;
• Indefiniteness of structural or positional language;
• Noninfringement based on a salt, stereoisomer or structural modification; and
• Expiration-based defenses if the patent term has ended.

The patent's strongest litigation position is against a product containing elagolix sodium itself. Claims 15, 21-26 and the corresponding method claims provide overlapping claim coverage. A generic applicant may still challenge the claims, but it would have difficulty relying solely on a formulation or labeling modification to avoid the core compound claim.

For a post-expiration ANDA, the principal remaining risks move to:

• Later Orange Book-listed patents;
• Method-of-use carve-outs;
• Combination-product patents;
• Formulation and solid-state patents; and
• Regulatory requirements for demonstrating pharmaceutical equivalence and bioequivalence.

Which companies are commercial competitors to elagolix?

Elagolix competes within the GnRH antagonist and hormonal suppression markets.

Product	Active ingredient	Sponsor	Principal use
Orilissa	Elagolix sodium	AbbVie	Endometriosis-associated pain
Oriahnn	Elagolix, estradiol, norethindrone acetate	AbbVie	Uterine fibroid-associated heavy menstrual bleeding
Myfembree	Relugolix, estradiol, norethindrone acetate	Myovant, Pfizer	Uterine fibroids and endometriosis
Orgovyx	Relugolix	Myovant, Pfizer	Prostate cancer
Lupron Depot	Leuprolide acetate	AbbVie	GnRH agonist indications
Yselty	Linzagolix	Theramex	Uterine fibroids in selected markets

Relugolix is the closest direct small-molecule competitor. It has a different chemical structure and separate patent estate. Leuprolide is a peptide GnRH agonist with different administration and pharmacology.

How strong is the patent estate for US 7,419,983?

The patent has high historical strength because it combines:

1. A broad genus claim;
2. Narrow claims to the clinical candidate;
3. Claims to sodium and calcium salts;
4. Composition claims;
5. Multiple treatment indications; and
6. Overlapping claim categories.

Its commercial strength is strongest during the composition patent term. After that term, the value shifts to later patents covering dosing, combinations, formulations and specific approved uses.

Dimension	Assessment
Chemical breadth	High
Coverage of elagolix sodium	Direct and strong under claim 15
Salt coverage	Broad under claims 1, 12-16 and related composition claims
Formulation specificity	Moderate to low in the patent itself
Method-of-use breadth	Broad across four listed conditions
Design-around difficulty	High for the active ingredient; lower for later formulation claims
Post-expiration value	Dependent on later patent families and regulatory exclusivity

What is the biosimilar risk for elagolix?

Biosimilar risk is not the primary concern because elagolix is a chemically synthesized small molecule, not a biologic. A competitor would generally pursue an ANDA under the Hatch-Waxman pathway rather than a biosimilar application under the Public Health Service Act.

The relevant competitive threat is generic elagolix sodium. Generic entry requires pharmaceutical-equivalence and bioequivalence work, along with resolution of listed patents and any method-of-use restrictions.

What generic launch scenarios exist?

At-risk launch

A generic applicant may launch after receiving FDA approval but before final resolution of patent litigation. This exposes the applicant to damages and potential injunctive relief if the patent holder prevails.

Noninfringing launch

The applicant may omit patented indications from its label, use a permissible skinny label and avoid unexpired formulation or combination patents. This strategy is most useful where the remaining patents cover methods rather than the active ingredient.

Post-expiration launch

The applicant may wait until expiration of the core compound patent and any relevant later patents. This reduces litigation risk but delays market entry.

Alternative-salt launch

An alternative salt may not avoid the patent if claim 1 or another claim covers pharmaceutically acceptable salts generally. Salt selection is therefore not a reliable design-around by itself.

What licensing deals affect elagolix?

Neurocrine Biosciences discovered and developed elagolix and entered into a collaboration with AbbVie. AbbVie obtained commercial rights in specified territories, while Neurocrine retained economic participation under the collaboration arrangements. The agreement covered development and commercialization of elagolix products, including the endometriosis and uterine fibroid programs.[5]

The licensing structure matters because patent ownership, NDA ownership, commercialization rights and royalty economics can be divided among different entities. A patent assignment search should therefore distinguish:

• Original applicant and inventor;
• Current patent owner;
• NDA holder;
• Commercial licensee; and
• Enforcement party.

What is the litigation status of US 7,419,983?

The core patent has reached or passed its base 20-year term calculated from the December 20, 2002 priority date. Current litigation exposure therefore depends primarily on whether patent-term adjustment extended the term and whether a later patent is asserted.

The most commercially material disputes for elagolix are likely to concern later patents covering:

• Endometriosis dosing;
• Long-term treatment;
• Estrogen or progestin combination therapy;
• Uterine fibroid treatment;
• Formulation and solid-state properties; and
• Generic ANDA labels.

A definitive litigation assessment must separate disputes involving Orilissa from disputes involving Oriahnn. The products contain related but different regulatory presentations, and an ANDA for elagolix monotherapy does not necessarily implicate every patent listed for the combination product.

Key Takeaways

• US 7,419,983 is a foundational elagolix patent.
• Claim 1 covers a broad substituted pyrimidinedione genus.
• Claim 15 expressly covers elagolix sodium.
• Claims 21-30 cover pharmaceutical compositions containing the claimed compounds.
• Claims 31-40 cover treatment of prostate cancer, benign prostatic hypertrophy, breast cancer and endometriosis.
• The patent includes direct coverage of sodium and calcium salts.
• The base term runs from the December 20, 2002 priority date, subject to patent-term adjustment.
• Elagolix is a small molecule, so generic rather than biosimilar competition is the relevant entry risk.
• Later patents, not only US 7,419,983, determine the practical launch date for generic Orilissa or combination-product competitors.
• The strongest infringement case concerns a product containing elagolix sodium itself.

FAQs About US Patent 7,419,983 and Elagolix

Does US 7,419,983 cover Orilissa?

Yes. Claim 15 specifically covers the sodium salt of the fluoro-methoxy elagolix compound used in Orilissa.

Does the patent cover elagolix calcium?

Yes. Claim 16 covers the calcium salt of the fluoro-methoxy compound, and related composition and method claims extend that coverage.

Is elagolix protected by a biologic patent?

No. Elagolix is a chemically synthesized small molecule. Generic entry is pursued through the ANDA pathway, not the biosimilar pathway.

Does a different elagolix salt automatically avoid infringement?

No. Claim 1 includes pharmaceutically acceptable salts, and dependent claims expressly cover sodium and calcium salts.

Does US 7,419,983 cover Oriahnn?

It covers the elagolix active ingredient component and compositions containing it within the claim scope. It does not, by itself, recite the complete estradiol and norethindrone acetate combination or every product-specific dosing limitation.

References

1. United States Patent No. 7,419,983. (2008). Substituted pyrimidinedione compounds. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2018). Orilissa approval letter and prescribing information. FDA.

3. U.S. Food and Drug Administration. (2020). Oriahnn approval letter and prescribing information. FDA.

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Orange Book.

5. Neurocrine Biosciences, Inc. (2010). Annual report and AbbVie collaboration disclosures. U.S. Securities and Exchange Commission.

Drugs Protected by US Patent 7,419,983

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Abbvie	ORIAHNN (COPACKAGED)	elagolix sodium,estradiol,norethindrone acetate; elagolix sodium	CAPSULE;ORAL	213388-001	May 29, 2020		RX	Yes	Yes	7,419,983		Y	Y
Abbvie	ORILISSA	elagolix sodium	TABLET;ORAL	210450-001	Jul 23, 2018		RX	Yes	No	7,419,983		Y	Y		MANAGEMENT OF MODERATE TO SEVERE PAIN ASSOCIATED WITH ENDOMETRIOSIS
Abbvie	ORILISSA	elagolix sodium	TABLET;ORAL	210450-002	Jul 23, 2018		RX	Yes	Yes	7,419,983		Y	Y		MANAGEMENT OF MODERATE TO SEVERE PAIN ASSOCIATED WITH ENDOMETRIOSIS

International Family Members for US Patent 7,419,983

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	407679
Australia	2004257639
Brazil	PI0412314
Canada	2531508
China	100424078