Details for Patent: 9,839,641

Which drugs does patent 9,839,641 protect, and when does it expire?

Patent 9,839,641 protects NUZOLVENCE and is included in one NDA.

This patent has thirty-five patent family members in thirty countries.

Summary for Patent: 9,839,641

Title:	Compounds and methods for treating bacterial infections
Abstract:	Compounds of formula (I), pharmaceutically acceptable salts thereof, and uses of the compounds of formula (I) for treating bacterial infections are disclosed.
Inventor(s):	Gregory Steven Basarab, Madhusudhan Reddy Gowravaram, Sheila Hauck, Fei Zhou
Assignee:	AstraZeneca UK Ltd , Entasis Therapeutics Inc
Application Number:	US15/353,325
Patent Claim Types: see list of patent claims	Use;

United States Drug Patent 9,839,641: Scope, Claims, Expiration and Patent Landscape

US Patent No. 9,839,641 protects antibacterial treatment methods using a spirocyclic compound class associated with zoliflodacin, formerly AstraZeneca's AZD0914 and later developed by Entasis Therapeutics and Innoviva. The patent is a method-of-use patent, not a conventional composition-of-matter, formulation or manufacturing patent. Its broadest claim covers treatment of bacterial infections with a large Markush genus of compounds. Narrower claims identify specific stereochemically defined compounds and target resistant Staphylococcus, Streptococcus, Haemophilus and Legionella infections.

The patent was granted Dec. 12, 2017. Based on its priority and filing history, the ordinary 20-year term is expected to run into April 2032, subject to any patent-term adjustment or extension reflected in the official USPTO record. The patent is not an Orange Book-listed patent for an FDA-approved product because zoliflodacin has not received FDA approval. Conventional Paragraph IV litigation therefore does not currently attach to this patent.

What drug does US 9,839,641 protect?

The patent protects a class of spirocyclic antibacterial compounds. The principal clinical compound associated with the patent is zoliflodacin.

Zoliflodacin is a first-in-class oral antibiotic designed to inhibit bacterial DNA gyrase and topoisomerase activity through a mechanism distinct from fluoroquinolones. It has been developed for bacterial infections, including uncomplicated gonorrhea caused by susceptible or drug-resistant Neisseria gonorrhoeae. The claims supplied for US 9,839,641 are broader than the current gonorrhea development program because they recite treatment of Gram-positive, Gram-negative and atypical bacterial infections.

The claimed chemical core contains:

• A spirocyclic quinoline-pyrimidinetrione framework.
• An oxazolidinone substituent.
• A fluorine or chlorine substituent on the fused aromatic system.
• Variable substituents at positions corresponding to R1, R2 and R3.
• Defined stereochemistry at the spirocyclic and oxazolidinone portions.

The patent therefore covers both the clinical candidate and a research genus containing numerous analogues.

How broad is claim 1 of US 9,839,641?

Claim 1 is a broad method-of-treatment claim. It requires:

1. A subject with a Gram-positive, Gram-negative or atypical bacterial infection.
2. Administration of an effective amount of a claimed compound.
3. A compound having the specified structural formula.
4. Substitution patterns satisfying the definitions for X, R1, R2 and R3.
5. A pharmaceutically acceptable salt, where applicable through the claim language and dependent species.

The variables are broad:

Variable	Claimed scope
X	Fluorine or chlorine
R1	Hydrogen, phenyl, cyano, tetrahydropyranyl, heteroaryl, cyclopropyl, ethynyl, vinyl or substituted C1-C3 alkyl
R2	Hydrogen, cyano, pyridinyl or substituted C1-C3 alkyl
R3	Hydrogen or C1-C3 alkyl
R10	Hydrogen, C1-C4 alkyl or 2-methoxyethyl
R11, R20, R21	Hydrogen or C1-C4 alkyl

The breadth comes primarily from the R1 and R2 definitions. R1 includes neutral, polar, lipophilic, heteroaryl, unsaturated and metabolically functionalized substituents. The specification presumably supports a medicinal-chemistry series rather than a single clinical compound.

Claim 1 does not require:

• A particular dose.
• A particular route of administration.
• Oral administration.
• A particular dosage form.
• Combination therapy.
• A particular infection site.
• A minimum level of antibacterial activity.
• A particular pathogen species.
• A specific duration of treatment.

A marketed product could potentially practice claim 1 if it contains a compound within the Markush scope and is administered to treat a qualifying bacterial infection.

What compounds are covered by claims 2 through 9?

Claims 2 through 8 narrow the substituent definitions. Claim 9 lists numerous expressly identified compounds.

Claims 2 through 5

Claims 2 through 5 restrict the alkoxy and oxime substituents:

• Claim 2 limits R10 to hydrogen, methyl, ethyl or 2-methoxyethyl.
• Claim 3 limits R11 to hydrogen or methyl.
• Claim 4 limits R20 to hydrogen, methyl or ethyl.
• Claim 5 limits R21 to hydrogen or methyl.

These claims have narrower literal coverage but remain genus claims because they continue to depend on the broad structural framework of claim 1.

Claim 6

Claim 6 provides a more detailed R1 list, including:

• Methyl and ethyl.
• Phenyl and benzyl.
• Fluoromethyl.
• Methoxymethyl.
• Allyl.
• Hydroxypropyl and fluoropropyl.
• Cyano.
• Oxime and methoxyimino groups.
• Methylthiomethyl and methylsulfonylmethyl.
• Azidomethyl.
• Pyridyl, pyrimidinyl, pyrazinyl and N-methyl-triazolyl groups.
• Ethynyl and vinyl groups.
• Hydroxyethyl and hydroxymethyl substituents.

This claim is important because it converts the functional language in claim 1 into a defined catalogue of substituents. It may be easier to enforce against a structurally close analogue where the accused compound falls within one of these enumerated groups.

Claim 7

Claim 7 narrows R2 to:

• Hydrogen.
• Methyl or ethyl.
• Fluoromethyl.
• Methoxymethyl.
• Hydroxymethyl.
• Oxime derivatives.
• Azidomethyl.
• Pyridinyl.
• Cyano.

Claim 8

Claim 8 limits R3 to hydrogen or methyl. This is a relatively narrow stereochemical and substitutional limitation compared with claim 1.

Claim 9

Claim 9 lists a large number of specific compounds. The species include fluorinated and chlorinated analogues and multiple oxazolidinone stereoisomers bearing:

• Methyl.
• Ethyl.
• Phenyl.
• Benzyl.
• Fluoromethyl.
• Methoxymethyl.
• Hydroxymethyl.
• Hydroxypropyl.
• Fluoropropyl.
• Tetrahydropyranyl.
• Pyridyl.
• Pyrazinyl.
• Pyrimidinyl.
• Triazolyl.
• Vinyl.
• Ethynyl.
• Azidomethyl.
• Methylthiomethyl.
• Methylsulfonylmethyl.
• Cyano.
• Oxime and methoxyimino groups.

The large species list strengthens the patent against an argument that the disclosure is limited to only one molecule. It also creates a fallback position if the broad Markush genus is challenged for lack of written description, enablement or obviousness.

The list contains apparent typographical and nomenclature inconsistencies, including repeated compounds, inconsistent ring-system names and misspellings such as "epidermis" for S. epidermidis and "Choro" or "Choro" variants in the supplied text. Those errors do not necessarily invalidate the patent. Their impact would depend on whether a skilled chemist could identify the intended structure from the specification, drawings, examples and accepted chemical nomenclature.

What infections are protected by US 9,839,641?

Claims 10 through 18 narrow the bacterial indications.

Claim	Covered infection or pathogen
10	Staphylococcus or Streptococcus
11	S. aureus, S. haemolyticus or S. epidermidis
12	S. aureus
13	Vancomycin- or methicillin-resistant S. aureus
14	S. pneumoniae, S. pyogenes or S. agalactiae
15	Haemophilus
16	H. influenzae
17	Legionella
18	Legionella infection allegedly caused by H. influenzae

Claim 18 is internally inconsistent. H. influenzae is a Haemophilus species, not a Legionella species. The error appears to be a drafting or dependency mistake. It may be corrected through a certificate of correction, reexamination, claim construction or another post-grant mechanism, but the patent text alone does not establish that any correction occurred.

Claims 13 and 23 are commercially relevant because they expressly cover treatment of resistant S. aureus, including MRSA and vancomycin-resistant S. aureus. These claims would be relevant to a product label or promotional use that specifically identifies those pathogens.

The claims are not limited to gonorrhea. A product used for gonorrhea could practice the broader method claims if the compound and treatment conditions satisfy the remaining elements, even though gonorrhea is not expressly listed in claims 10 through 18.

What does claim 19 protect?

Claim 19 is a second independent method claim directed to a single illustrated compound or defined structure, plus pharmaceutically acceptable salts.

Unlike claim 1, claim 19 does not use the R1, R2 and R3 Markush variables. It is therefore narrower chemically and likely corresponds to a lead or clinical candidate compound. Based on the disclosed compound series and the zoliflodacin development history, claim 19 is directed to the specific clinical compound associated with this patent family.

Claims 20 through 28 apply the same pathogen limitations to the claim 19 compound:

• Staphylococcus and Streptococcus infections.
• S. aureus, including resistant S. aureus.
• S. pneumoniae, S. pyogenes and S. agalactiae.
• Haemophilus infections.
• H. influenzae.
• Legionella infections.
• The same apparent pathogen inconsistency in claim 28.

Claim 19 is likely the most important claim for product-specific enforcement because it covers a single defined compound rather than a broad genus. Its practical value depends on whether the commercial product's exact stereochemistry, salt form and chemical structure fall within the illustrated structure.

When does US 9,839,641 expire?

The expected ordinary expiration date is approximately April 2032.

Event	Date or status
Earliest reported priority	April 15, 2011
U.S. grant	Dec. 12, 2017
Patent number	US 9,839,641
Expected 20-year term endpoint	Approximately April 2032
Patent-term adjustment	Must be confirmed from the USPTO patent record
Patent-term extension	No approved-product extension currently identified
Regulatory status	No FDA approval for zoliflodacin identified
Orange Book status	No listed drug or listed patent status identified

The precise expiration date should be taken from the USPTO patent record because the effective term can change through patent-term adjustment. A patent-term extension under 35 U.S.C. § 156 requires an approved product and regulatory eligibility. With no FDA-approved product, such an extension does not presently provide a meaningful pathway for this patent.

The patent could also be affected by terminal disclaimers, disclaimer filings, reexamination, post-grant review or later continuation practice. Those issues must be assessed against the complete prosecution and family record.

Is US 9,839,641 listed in the Orange Book?

No Orange Book listing is expected for US 9,839,641 because the patent is tied to an unapproved antibacterial development program rather than an FDA-approved drug product.

The Orange Book lists patents associated with approved new drug applications. It does not operate as a general registry of all pharmaceutical patents. A patent can be legally enforceable without appearing in the Orange Book, but an Orange Book listing creates the specific notice and litigation framework associated with ANDA Paragraph IV certifications.

For US 9,839,641:

• No approved NDA is identified for the claimed compound.
• No reference listed drug is available for an ANDA directed to zoliflodacin.
• No routine Paragraph IV certification is currently expected.
• A future NDA approval could create an opportunity to list eligible patents if the statutory and regulatory requirements are satisfied.
• A patent claiming only methods of use may face listing limitations if the approved labeling does not correspond to the patented method.

Have generic manufacturers challenged US 9,839,641?

No conventional Paragraph IV challenge is expected while the claimed product remains unapproved.

A future generic entrant would need an approved reference product and would likely evaluate several routes:

1. An ANDA with Paragraph IV certification after an FDA reference product is listed.
2. A 505(b)(2) application relying partly on published or innovator data.
3. A separate antibacterial product with a different active compound.
4. A product that avoids the exact claim 19 structure but potentially remains within the claim 1 genus.
5. A post-expiration launch based on the expected 2032 patent endpoint.

An ANDA applicant could challenge validity for lack of written description, enablement, anticipation or obviousness. The broad genus in claim 1 is more exposed to such attacks than the expressly listed species in claim 9 or the single-compound claim 19.

How strong is the patent estate for zoliflodacin?

US 9,839,641 is strategically useful but does not constitute a complete product estate by itself.

Strengths

• Claim 1 covers a broad structural genus.
• Claim 9 supplies numerous specific fallback compounds.
• Claim 19 appears directed to the clinical compound.
• The method claims cover resistant bacterial infections.
• The patent predates the current clinical development program and has substantial remaining term.
• The broad claims may reach analogues selected by a competitor for commercial development.

Weaknesses

• The patent is primarily a method-of-use patent.
• It does not, on the supplied claims, independently claim a composition, tablet, capsule, injectable formulation or manufacturing process.
• It does not recite a specific dose, regimen or route.
• The broad genus may face written-description and enablement scrutiny.
• The pathogen claims contain apparent drafting defects.
• The lack of FDA approval prevents current Orange Book leverage.
• The commercial compound may require separate protection for crystalline form, salt, formulation, process and clinical indication.

The strongest enforcement position would generally involve a commercial product using the exact claim 19 compound for a labeled indication that falls within claims 20 through 28. The broader claim 1 could reach a competing analogue, but its validity and construction would require a detailed comparison of the accused structure with the Markush definitions.

What formulation patents protect zoliflodacin?

US 9,839,641 does not contain formulation claims in the supplied claim set. It claims administering an effective amount of a compound, without specifying:

• Tablet composition.
• Capsule composition.
• Coating.
• Excipients.
• Particle size.
• Polymorph.
• Amorphous form.
• Salt or solvate selection beyond pharmaceutically acceptable salts.
• Release profile.
• Food-effect mitigation.
• Pharmaceutical packaging.
• Stability conditions.

A complete commercial patent estate would normally be reviewed for separate applications covering the active pharmaceutical ingredient, polymorphs, salts, formulations, dosing regimens, combination therapy, synthesis and specific treatment indications. Those rights are distinct from US 9,839,641 and cannot be inferred from this patent's claims alone.

What licensing deal affects the patent?

Zoliflodacin originated at AstraZeneca under the AZD0914 program. Entasis Therapeutics obtained rights to develop the compound, and Innoviva later became the parent company associated with the program. The commercial allocation of patent rights, development rights, royalties and milestone obligations must be distinguished from ownership of US 9,839,641.

The relevant business issue is that a licensee or successor developer can control commercialization without being the original patent applicant. Patent ownership, exclusive field rights, sublicensing rights and royalty obligations should therefore be checked separately in the assignment database and transaction agreements.

What litigation affects US 9,839,641?

No Paragraph IV litigation is expected because there is no approved reference drug and no Orange Book listing identified for the patent.

The principal litigation risks are instead:

• A future validity challenge by an ANDA or 505(b)(2) applicant.
• A declaratory-judgment action involving a competing compound.
• A dispute over whether a marketed salt or stereoisomer falls within claim 19.
• A written-description or enablement challenge to claim 1.
• A claim-construction dispute involving the spirocyclic nomenclature.
• A challenge based on the patent's apparent pathogen errors.

No biosimilar pathway applies. Zoliflodacin is a chemically synthesized small molecule, not a biologic subject to the Public Health Service Act biosimilar framework.

What generic launch scenarios exist?

Launch before patent expiration

A pre-2032 launch would require one of the following:

• Successful invalidity or noninfringement litigation.
• A settlement permitting an earlier entry date.
• A product outside the patented chemical scope.
• A different active ingredient.
• A regulatory pathway that does not rely on the patented compound.

Launch after patent expiration

A post-expiration launch is the most straightforward scenario for the claimed compound, assuming no later patents covering the active ingredient, formulation, salt, polymorph, manufacturing process or approved indication.

Design-around launch

A competitor could attempt to:

• Select a compound outside the R1, R2 or R3 definitions.
• Use a different stereoisomer.
• Develop a different oxazolidinone substituent.
• Avoid the exact structure of claim 19.
• Commercialize a different gyrase or topoisomerase inhibitor.

Design-around analysis must account for literal infringement, doctrine of equivalents and any separate continuation or divisional patents.

Key Takeaways

• US 9,839,641 is a spirocyclic antibacterial method-of-use patent associated with zoliflodacin.
• Claim 1 covers a broad Markush genus with fluorine or chlorine and extensive R1, R2 and R3 substitution options.
• Claim 9 lists numerous specific compounds and stereoisomers.
• Claim 19 appears to cover the single clinical compound, with claims 20 through 28 adding pathogen limitations.
• The patent does not contain formulation or manufacturing claims in the supplied claim set.
• The expected ordinary expiration is approximately April 2032, subject to USPTO patent-term adjustment.
• No Orange Book listing or Paragraph IV challenge is expected while zoliflodacin remains unapproved.
• The main validity exposure is the breadth of claim 1, while claim 19 and the species in claim 9 provide stronger fallback positions.
• Future commercial risk will depend heavily on later patents covering salts, polymorphs, formulations, manufacturing and approved-use regimens.
• Biosimilar risk is irrelevant because zoliflodacin is a small-molecule antibacterial.

FAQs

Does US 9,839,641 claim zoliflodacin itself?

The patent includes a broad genus and a separate independent claim directed to a single illustrated compound. The latter is associated with the clinical zoliflodacin structure and is the most relevant product-specific claim.

Can a generic company file Paragraph IV against this patent now?

Not in the ordinary manner because the claimed product is not associated with an FDA-approved reference listed drug or an identified Orange Book listing.

Does the patent cover oral zoliflodacin tablets?

It does not expressly claim tablets or an oral dosage form. It claims administering an effective amount of the compound. Separate formulation claims would be needed for specific tablet compositions or delivery technologies.

Are MRSA and vancomycin-resistant S. aureus within the claimed scope?

Yes. Claims 13 and 23 specifically recite S. aureus resistant to methicillin or vancomycin.

Could a different stereoisomer avoid infringement?

Potentially. The patent recites defined stereochemistry and expressly lists numerous stereoisomers. A compound with a different stereochemical configuration must be compared against each limitation of the asserted claim, including the broad genus and any applicable equivalents analysis.

References

1. AstraZeneca. (2018). AstraZeneca enters agreement with Entasis Therapeutics for global rights to develop and commercialize AZD0914. AstraZeneca corporate news release.

2. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

3. Innoviva, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.

4. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,839,641, spirocyclic compounds and methods of use thereof. U.S. Department of Commerce.

5. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term extension records. U.S. Department of Commerce.

Drugs Protected by US Patent 9,839,641

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Entasis Therap	NUZOLVENCE	zoliflodacin	FOR SUSPENSION;ORAL	219491-001	Dec 12, 2025		RX	Yes	Yes	9,839,641					TREATMENT OF UNCOMPLICATED UROGENITAL GONORRHEA DUE TO NEISSERIA GONORRHOEAE

International Family Members for US Patent 9,839,641

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	094565
Australia	2014208965
Brazil	112015017519
Canada	2897887
China	105229012
Cyprus	1122805