Details for Patent: 7,919,499

Which drugs does patent 7,919,499 protect, and when does it expire?

Patent 7,919,499 protects VIVITROL and is included in one NDA.

This patent has eighteen patent family members in eleven countries.

Summary for Patent: 7,919,499

Title:	Naltrexone long acting formulations and methods of use
Abstract:	The inventions described herein arose from unexpected discoveries made during clinical trials with a long acting formulation of naltrexone. As such, the invention includes a method for treating an individual in need of naltrexone comprising the step of parenterally administering a long acting formulation comprising naltrexone and to the use of naltrexone in the manufacture of medicaments for use in such methods.
Inventor(s):	Elliot Ehrich
Assignee:	Alkermes Pharma Ireland Ltd
Application Number:	US11/083,167
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,919,499
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

United States Patent 7,919,499: Naltrexone Microsphere Claims, Patent Scope, and Competitive Landscape

U.S. Patent No. 7,919,499 protects selected clinical uses of long-acting parenteral naltrexone formulated with a polylactide-co-glycolide polymer, commonly referred to as PLGA. Its core protection is a pharmacokinetic treatment regimen, not the abstract use of naltrexone or every injectable naltrexone formulation. The claims require specific dose ranges, relative serum AUC performance compared with oral naltrexone, PLGA, and, in dependent claims, repeated administration, injection, alcohol dependence, and treatment duration.

The patent is closely associated with Alkermes’ extended-release injectable naltrexone product Vivitrol. It is materially stronger against a competing long-acting PLGA naltrexone injection than against oral naltrexone, non-PLGA implants, or formulations that cannot demonstrate the claimed AUC relationship.

What does U.S. Patent 7,919,499 cover?

The patent covers methods of treating a person by administering a long-acting naltrexone formulation parenterally. The formulation must contain:

• Naltrexone in a specified amount;
• A biocompatible PLGA polymer;
• A serum exposure level measured by AUC relative to 50 mg/day oral naltrexone; and
• A sustained-release profile in certain dependent claims.

The two independent claims divide the claimed technology into high-dose and lower-dose regimens.

Claim	Naltrexone dose	Required relative serum AUC	Polymer	Principal subject
1	About 310-480 mg	About 3 times oral 50 mg/day	PLGA	Parenteral long-acting treatment
14	About 190-240 mg	About 2 times oral 50 mg/day	PLGA	Parenteral long-acting treatment
5	About 380 mg	About 3.3 times oral 50 mg/day	PLGA	Narrower version of claim 1
15	About 190 mg	About 2 times oral 50 mg/day	PLGA	Narrower version of claim 14

The claims are method claims. They do not independently claim the microsphere composition, a manufacturing process, a vial, a syringe, or a broad pharmaceutical composition.

How should claim 1 be construed?

Claim 1 requires every material limitation below:

1. Treatment of an individual in need of naltrexone.
2. Parenteral administration.
3. A long-acting formulation.
4. Approximately 310 mg to approximately 480 mg of naltrexone.
5. A biocompatible polymer.
6. A serum naltrexone AUC approximately three times that produced by 50 mg/day oral administration.
7. The polymer must be PLGA.

A product or regimen that omits any required limitation may avoid literal infringement of claim 1. The most important limitations are the PLGA requirement and the pharmacokinetic AUC limitation.

Dose range

The phrase "about 310 mg to about 480 mg" gives the claim a numerical range with potential flexibility at both endpoints. It does not necessarily cover all long-acting injections containing less than 310 mg or more than 480 mg. Claim 5 narrows the range to approximately 380 mg and requires an approximately 3.3-fold AUC increase.

The dose is the amount of naltrexone, not necessarily the total mass of the microsphere product. A formulation containing approximately 35% naltrexone by weight, as recited in claim 13, would contain a substantially larger total microsphere mass than the stated naltrexone dose.

Parenteral administration

"Parenterally administering" generally covers administration that bypasses the gastrointestinal tract, including injection. Claim 12 narrows the method to injection, but claim 1 is broader on route if the route qualifies as parenteral.

The claims are not limited expressly to intramuscular injection in the independent claims. Claim 12 confirms injection as a specific embodiment, while the commercial Vivitrol product is administered by intramuscular gluteal injection.[2]

Serum AUC requirement

The AUC limitation is central. A competing product must be evaluated against the specified pharmacokinetic comparator: 50 mg/day oral naltrexone.

The claim does not merely require a dose that is nominally equivalent to oral therapy. It requires a serum exposure relationship. That creates several enforcement issues:

• The comparator oral regimen must be defined consistently.
• The relevant sampling period must be established.
• AUC may vary between subjects and study populations.
• "About three times" and "about 3.3 times" create a range rather than a single numerical threshold.
• The formulation must be tested under conditions that reasonably correspond to the claimed regimen.

A competitor could challenge infringement by showing that its formulation does not achieve the required AUC, even if it uses PLGA and contains a similar quantity of naltrexone. Conversely, a formulation could face infringement risk if its clinical pharmacokinetic profile falls within the claimed relative exposure range, even if it uses a different microsphere size or release-control parameter.

What do claims 2 through 13 add?

The dependent claims create narrower treatment scenarios and strengthen the patent against commercial regimens that resemble the clinical use of Vivitrol.

Claim	Added limitation	Practical effect
2	Administration every four weeks for at least about 24 weeks; no oral naltrexone within five or more days before administration	Targets repeated monthly treatment without recent oral pretreatment
3	Release for at least two weeks	Covers sustained release beyond an ordinary short-acting injection
4	Release for about four weeks	Closely tracks monthly treatment
5	Approximately 380 mg and approximately 3.3-fold AUC	Narrows the high-dose regimen
6	Administration over approximately 24 weeks or longer	Requires an extended course
7	Second administration at least approximately seven days after the first	Covers repeat dosing
8	Second formulation substantially similar to first	Narrows repeat dosing
9	Second formulation the same as first	Narrowest repeat-dosing version
10	Patient has alcohol dependence	Disease-specific embodiment
11	No initial oral naltrexone dose	Removes an oral lead-in requirement
12	Injection	Narrows parenteral administration
13	Approximately 35% naltrexone by weight	Formulation-composition limitation

Claim 2 is commercially important because it combines a four-week interval with treatment lasting at least 24 weeks. Claim 11 is also relevant to Vivitrol-style treatment because the FDA labeling does not require an oral naltrexone test dose before initiating extended-release injectable naltrexone, although opioid-free status and clinical assessment remain important.[2]

Claims 7 through 9 create overlapping repeat-administration protection. Claim 7 is broad because the second dose need only occur at least approximately seven days after the first. Claims 8 and 9 add formulation similarity or identity.

How does claim 14 differ from claim 1?

Claim 14 covers a lower-dose regimen:

• Approximately 190 mg to approximately 240 mg of naltrexone;
• Approximately twice the serum AUC of oral 50 mg/day naltrexone; and
• A PLGA polymer in a long-acting parenteral formulation.

Claim 15 narrows the dose to approximately 190 mg.

This lower-dose branch is commercially and strategically significant because it prevents a simple design-around based solely on reducing the dose below claim 1’s 310 mg floor. A competitor using approximately 190-240 mg could still face claim 14 if it also meets the PLGA, parenteral, long-acting, and AUC limitations.

The patent therefore divides the relevant dose space into at least two protected bands:

• Approximately 190-240 mg at approximately two times oral exposure; and
• Approximately 310-480 mg at approximately three times oral exposure.

A formulation between approximately 240 mg and 310 mg may fall outside the literal dose ranges of claims 1 and 14, subject to the interpretation of "about," prosecution history, and potential equivalents analysis.

What formulations are protected by U.S. Patent 7,919,499?

The patent protects methods using long-acting formulations that contain PLGA. PLGA is a biodegradable copolymer of lactic acid and glycolic acid widely used in injectable microspheres and depot formulations.

The claims reach formulations with:

• Naltrexone embedded in PLGA microspheres;
• Sustained release over at least two weeks;
• Approximately four-week release;
• Approximately 35% naltrexone loading; and
• Repeated parenteral administration.

The claims do not expressly require a particular PLGA molecular weight, lactide-to-glycolide ratio, particle size, solvent system, manufacturing process, or injection device. Those characteristics may matter to infringement only if they affect whether the accused formulation satisfies the express claim limitations.

A formulation using a non-PLGA biodegradable polymer may present a stronger literal noninfringement position. Potential exposure would depend on whether the patent’s polymer limitation is treated as essential and whether an equivalents theory is viable.

What is the Orange Book status of U.S. Patent 7,919,499?

U.S. Patent 7,919,499 has been associated with Vivitrol, the FDA-approved extended-release injectable suspension of naltrexone.[1] The Orange Book is the principal public FDA record for patents submitted by an NDA holder for an approved drug product.[1]

The relevant regulatory structure is:

Item	Product or pathway
Drug	Extended-release injectable naltrexone
Brand	Vivitrol
Active ingredient	Naltrexone
Sponsor	Alkermes, Inc. or affiliated Alkermes entity
FDA pathway	New drug application
Dosage form	Extended-release injectable suspension
Patent relevance	Method-of-use and formulation-related protection
Generic pathway	ANDA, subject to product sameness and listed-patent certifications

An Orange Book listing does not itself establish that every claim is valid or enforceable. It does, however, create a patent-certification issue for an ANDA applicant seeking approval of a product that relies on the listed drug.

For an injectable complex formulation, an ANDA applicant would also need to address sameness or equivalent performance, including formulation, route, dosage form, release characteristics, and bioequivalence requirements. FDA approval risk and patent litigation risk would arise together but are legally distinct.

When does U.S. Patent 7,919,499 lose exclusivity?

The patent issued on April 5, 2011.[3] Its patent term is not calculated as 20 years from the issue date. For a U.S. utility patent, the relevant term generally runs from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, patent-term extension, and other statutory provisions.[4]

The public patent record identifies earlier priority filings associated with the naltrexone microsphere technology. The effective expiration date must therefore be determined from the USPTO continuity data, patent-term adjustment record, any terminal disclaimer, and any FDA patent-term extension reflected in the official records.[3][4]

A practical diligence conclusion is that the patent should not be analyzed in isolation from the broader Vivitrol patent estate. Even if 7,919,499 has expired or is approaching expiration, later-issued patents may continue to affect a generic or follow-on injectable product. The relevant freedom-to-operate date is the latest enforceable patent that covers the proposed product or its labeled use, not the expiration date of one patent.

Which companies are challenging Vivitrol exclusivity?

Publicly visible competition has historically been stronger in oral naltrexone than in long-acting injectable naltrexone.

Oral generic manufacturers

Naltrexone tablets are available from multiple generic manufacturers. Oral products generally do not practice the asserted method claims of U.S. Patent 7,919,499 because they lack parenteral administration, PLGA, and the claimed sustained-release formulation.

Long-acting injectable developers

A competing long-acting injectable naltrexone product would face three categories of barriers:

1. Patent claims covering the formulation or treatment method.
2. FDA requirements for a complex injectable suspension.
3. Manufacturing scale-up and batch-to-batch release testing for microsphere products.

No biosimilar pathway applies. Naltrexone is a small-molecule active ingredient, and Vivitrol is not regulated as a biologic. The relevant abbreviated route is generally an ANDA or, depending on the product and regulatory characterization, a 505(b)(2) application.

What Paragraph IV risks exist for a generic Vivitrol product?

A generic applicant could submit a Paragraph IV certification asserting that a listed patent is invalid, unenforceable, or not infringed. The patent claims most likely to create Paragraph IV issues are:

• Claim 1, for the broad high-dose PLGA regimen;
• Claim 5, for approximately 380 mg and approximately 3.3-fold AUC;
• Claims 2 and 4, for monthly repeat treatment and four-week release;
• Claim 10, for alcohol dependence; and
• Claim 14, for the lower-dose PLGA regimen.

A Paragraph IV challenge would likely focus on:

• Whether the claimed AUC relationship is inherent or anticipated;
• Whether "about" renders the numerical limitations indefinite;
• Whether prior art disclosed a PLGA naltrexone depot with the claimed dose and release profile;
• Whether the patent adequately describes and enables the claimed pharmacokinetic range;
• Whether the accused product’s label induces performance of the treatment method; and
• Whether the listed claims remain enforceable on the proposed launch date.

A generic label that omits alcohol-dependence language might avoid claim 10 but would not necessarily avoid claims 1 or 14, which contain no alcohol-dependence limitation.

What patent litigation affects Vivitrol and naltrexone?

Patent litigation risk is likely to concentrate on the full Vivitrol estate rather than on 7,919,499 alone. An ANDA filing directed to extended-release injectable naltrexone can trigger a patent-owner response under the Hatch-Waxman framework if the applicant makes a Paragraph IV certification.[5]

The main litigation theories would include:

• Invalidity based on prior art microspheres, depot injections, or naltrexone pharmacokinetics;
• Noninfringement based on dose, polymer, AUC, release period, or treatment-label differences;
• Indefiniteness of "about," "long acting," and relative AUC language;
• Lack of written description or enablement for the claimed dose and exposure ranges;
• Patent-term or terminal-disclaimer defenses; and
• Regulatory non-infringement based on a carve-out label.

A settlement could defer generic entry, permit an authorized generic, or allow a license under specified conditions. No reliable conclusion about a particular settlement should be drawn from the claim text alone. Settlement terms, if any, must be evaluated from court filings and FDA approval records.

How strong is the patent estate for Vivitrol?

U.S. Patent 7,919,499 has meaningful but bounded scope.

Strengths

• It claims the commercially relevant PLGA depot platform.
• It uses pharmacokinetic limitations that can map to clinical data.
• It covers both high-dose and lower-dose regimens.
• Dependent claims reach monthly administration and treatment lasting at least 24 weeks.
• The claims do not require alcohol dependence in the independent claims.

Weaknesses

• The patent has method claims rather than broad composition claims.
• A competitor may design around PLGA, dose, release duration, or AUC.
• Pharmacokinetic claim limitations can create factual disputes.
• "About" ranges may produce claim-construction and indefiniteness challenges.
• The enforceable term may be limited by the earliest effective filing date.

The estate is strongest against a product that intentionally replicates Vivitrol’s 380 mg PLGA microsphere profile and monthly injection schedule. It is weaker against oral naltrexone, non-PLGA depots, materially different doses, and products with a different pharmacokinetic profile.

What generic launch scenarios exist?

Scenario	Likely patent exposure	Commercial timing implication
Oral naltrexone tablets	Low exposure to these claims	Existing generic competition
Non-PLGA injectable depot	Lower literal exposure, subject to other patents	Requires separate FDA and FTO analysis
PLGA depot below approximately 190 mg	Potentially outside claims 1 and 14	May trigger other estate claims
PLGA depot at approximately 190 mg	Direct claim 14 and 15 risk	Paragraph IV likely
PLGA depot at approximately 380 mg	Direct claim 1 and 5 risk	Highest exposure
Monthly PLGA injection for alcohol dependence	Claims 1, 2, 4, 5, and 10 risk	Strongest infringement profile
Product with different label omitting alcohol dependence	Claim 10 risk may decrease	Independent claims remain relevant

What manufacturing and geographic barriers remain?

The core manufacturing barrier is reproducible production of injectable PLGA microspheres with controlled particle size, drug loading, residual solvent levels, sterility, syringeability, and release kinetics. A manufacturer must also demonstrate consistent AUC and depot duration across batches.

U.S. patent protection does not automatically determine rights in Europe, Japan, Canada, or other markets. Patent family members must be reviewed separately for:

• National-phase status;
• Claim scope;
• Patent-term adjustment or supplementary protection;
• Opposition or revocation history;
• Orange Book-equivalent listings; and
• Local approval requirements for injectable microspheres.

A U.S. noninfringement position therefore does not establish freedom to operate globally.

Key Takeaways

• U.S. Patent 7,919,499 is a method patent directed to long-acting parenteral PLGA naltrexone.
• Claim 1 targets approximately 310-480 mg with approximately three times the oral AUC.
• Claim 14 targets approximately 190-240 mg with approximately two times the oral AUC.
• Claim 5 maps closely to a 380 mg monthly regimen and approximately 3.3-fold AUC.
• Claims 2, 4, and 6 add commercially relevant monthly and 24-week treatment requirements.
• Oral naltrexone generics generally do not practice the principal limitations.
• A long-acting PLGA injectable designed to replicate Vivitrol has the highest Paragraph IV and infringement exposure.
• Vivitrol is a small-molecule drug, so biosimilar analysis is not applicable.
• The patent’s expiration must be assessed through the continuity chain, patent-term adjustment, terminal-disclaimer, and FDA extension records.
• Later Vivitrol patents may remain relevant after the expiration or unenforceability of this patent.

FAQs

Does U.S. Patent 7,919,499 cover oral naltrexone tablets?

No. The independent claims require parenteral administration, a long-acting formulation, and PLGA. Oral tablets generally do not satisfy those limitations.

Does the patent cover all injectable naltrexone products?

No. The claims require a PLGA polymer and specified dose and AUC characteristics. An injectable product using another polymer or a materially different pharmacokinetic profile may fall outside the literal claims.

Can a generic avoid claim 10 by removing alcohol dependence from its label?

Potentially, but removing the alcohol-dependence indication would not necessarily avoid claims 1 or 14. Those independent claims do not limit treatment to alcohol dependence.

Is a 380 mg injectable automatically within the patent claims?

No. Dose alone is insufficient. The product must also satisfy the long-acting, parenteral, PLGA, and relative serum AUC limitations.

Is a 505(b)(2) applicant exposed to the same patent risks as an ANDA applicant?

A 505(b)(2) applicant can face similar patent and method-of-use issues, but the filing strategy, certifications, labeling, and litigation posture differ from an ANDA. The applicable risk depends on the proposed formulation, reliance on Vivitrol data, and listed-patent certifications.

References

1. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

2. U.S. Food and Drug Administration. (2023). Vivitrol (naltrexone for extended-release injectable suspension) prescribing information. Alkermes, Inc. https://www.accessdata.fda.gov/drugsatfda_docs/label/

3. U.S. Patent and Trademark Office. (2011). U.S. Patent No. 7,919,499, long acting naltrexone formulations. https://patents.google.com/patent/US7919499

4. U.S. Patent and Trademark Office. (2024). Manual of patent examining procedure, Chapter 2700: Patent term. https://www.uspto.gov/web/offices/pac/mpep/mpep-2700.html

5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions and Paragraph IV patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/paragraph-four-patent-certifications

Drugs Protected by US Patent 7,919,499

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alkermes	VIVITROL	naltrexone	FOR SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	021897-001	Apr 13, 2006		RX	Yes	Yes						PREVENTION OF RELAPSE TO OPIOID DEPENDENCE, FOLLOWING OPIOID DETOXIFICATION
Alkermes	VIVITROL	naltrexone	FOR SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	021897-001	Apr 13, 2006		RX	Yes	Yes						TREATMENT OF ALCOHOL DEPENDENCE

International Family Members for US Patent 7,919,499

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005239989
Canada	2563086
China	103251597
China	1946353
European Patent Office	1740120
European Patent Office	2386269
United Kingdom	0304637