US Patent 9,309,245: Scope, Claims, Durlobactam Coverage and Patent Landscape

US Patent 9,309,245 is a composition-of-matter patent directed to substituted bridged bicyclic beta-lactamase inhibitors based on the 1,6-diazabicyclo[3.2.1]octane scaffold. The claim set covers broad chemical genera, defined subgenera, named species, pharmaceutically acceptable salts, and pharmaceutical compositions.

The patent is commercially important because the claimed scaffold includes durlobactam, the beta-lactamase inhibitor component of Xacduro (sulbactam/durlobactam), approved by the FDA in 2023 for hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex.[1] The patent issued April 12, 2016, from an application claiming priority to a December 23, 2013 filing. Its ordinary 20-year patent term runs to December 23, 2034, subject to any applicable patent-term adjustment or extension recorded by the USPTO.[2]

What does US Patent 9,309,245 protect?

The patent protects substituted 1,6-diazabicyclo[3.2.1]octane compounds containing a sulfate or hydrogen sulfate functionality and a lactam-containing bridged bicyclic core.

The principal structural elements are:

Claim element	Scope
Core	Bridged 1,6-diazabicyclo[3.2.1]octane system
Key functionality	7-oxo lactam and sulfate or hydrogen sulfate group
Stereochemistry	Claims 16 through 18 identify the relevant 2S,5R configuration
R1 substituent	Carbamoyl, cyano, hydroxymethyl-derived alkyl, methoxymethyl, or related substituents
R2/R3 substituents	Hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cyano, carbamoyl, ester and substituted derivatives
Salts	Pharmaceutically acceptable salts, including sodium salts
Product form	Individual compounds and pharmaceutical compositions

The claim architecture is characteristic of a pharmaceutical composition-of-matter patent. Claim 1 establishes a broad Markush genus. Claims 2 through 15 narrow the genus by formula and substituent selection. Claims 16 through 18 identify individual compounds or a defined list of species. Claim 19 covers pharmaceutical compositions. Claim 20 narrows the R1 group to carbamoyl or cyano.

How broad is claim 1 of US 9,309,245?

Claim 1 is broad in chemical scope but constrained by the bridged bicyclic core, the formula Ia arrangement, substituent exclusions, and the requirement that R2 and R3 are not both hydrogen.

The claim reaches compounds in which:

R1 is carbamoyl, cyano, or a substituted C1-C3 alkyl group;
R2 and R3 may independently contain alkyl, cycloalkyl, alkoxy, carbamoyl, ester, cyano, or unsaturated groups;
substituents may include amino, hydroxy, halo, alkoxy, heterocyclyl, heteroaryl and carbonyl-containing groups;
the compounds may be isolated as pharmaceutically acceptable salts.

The two express provisos narrow the claim:

R2 and R3 cannot both be hydrogen.
If R1 is carbamoyl, neither R2 nor R3 may also be carbamoyl.

These limitations matter for validity and infringement analysis. A compound with the claimed core but unsubstituted R2 and R3 would fall outside claim 1. A compound with carbamoyl at R1 and another carbamoyl substituent at R2 or R3 would also be excluded from the independent claim.

Which dependent claims are most commercially significant?

Claims 2 through 15 create progressively narrower fallback positions. Claims 16 through 18 are likely the most relevant to a marketed compound because they move from functional Markush language to specific molecular structures.

Claims 2 through 6: Formula III and R2 substitution

Claims 2 and 3 cover Formula III compounds. Claim 3 permits R2 and R3 to contain selected alkyl, cycloalkyl and carbamoyl groups, including groups substituted with a siderophore.

Claims 4 through 6 cover Formula V compounds. Claim 5 narrows R2 to methyl, ethyl, isopropyl or cyclopropyl, optionally substituted with hydroxy or C1-C3 alkoxy. Claim 6 limits R2 to methyl.

This group provides protection for relatively small hydrophobic substitutions on the bridged core. The methyl embodiment in claim 6 is particularly narrow and easier to compare against a commercial active ingredient than the broader genus in claim 1.

Claims 7 through 11: Formula IV and R3 substitution

Claims 7 through 11 cover Formula IV compounds with variation at R3. The permitted R3 groups include:

methyl;
ethyl;
isopropyl;
cyclopropyl;
carbamoyl;
substituted carbamoyl;
hydroxymethyl-derived groups;
methoxymethyl.

Claim 11 is the narrowest and most commercially useful species-level limitation in this group. It identifies R3 as methyl, -CH2OCH3, or -CONH2.

Claims 12 through 15: R1 restrictions

Claims 12 through 15 narrow R1 to carbamoyl, cyano, hydroxymethyl-derived alkyl and methoxymethyl groups.

Claim 14 limits R1 to -CH2OCH3 or -CONH2. Claim 15 then combines selected R1, R2 and R3 substituents, including:

R1 as methoxymethyl or carbamoyl;
R2 as hydrogen or methyl;
R3 as hydrogen, methyl or carbamoyl;
an exclusion where R2 and R3 are both hydrogen;
additional restrictions involving carbamoyl substitution.

These claims are important because they combine the substitution patterns most closely associated with development-stage DBO inhibitors.

Does US 9,309,245 cover durlobactam?

The patent’s claim set is directed to the chemical class that includes durlobactam-type sulfate DBO beta-lactamase inhibitors. Durlobactam is a cyclic boronate-free diazabicyclooctane beta-lactamase inhibitor administered as a sulfate salt with sulbactam in Xacduro.[1]

The supplied claim text does not display the chemical drawings for claims 2, 4, 7, 16 and 17. That omission prevents a definitive structure-to-claim mapping for those claims from the text alone. The compound names in claim 18, however, confirm that the patent expressly claims numerous 2S,5R sulfate or hydrogen sulfate derivatives, including carbamoyl, cyano, methyl, methoxymethyl and amino-substituted analogs.

A product-level freedom-to-operate opinion would therefore require:

the issued patent drawings;
the complete prosecution history;
the FDA-approved durlobactam structure and salt form;
any terminal disclaimer;
any patent-term adjustment;
later patents directed specifically to durlobactam formulations, combinations or manufacturing processes.

What pharmaceutical compositions are protected?

Claim 19 covers a pharmaceutical composition containing a Formula III compound or pharmaceutically acceptable salt with a carrier, diluent or excipient.

This is narrower than a product claim but still commercially relevant. It can cover an injectable formulation containing a claimed DBO inhibitor, provided the active ingredient falls within claim 2 and the formulation includes conventional pharmaceutical excipients.

The claim does not expressly require:

sulbactam;
intravenous administration;
a specific dose;
a particular vial or reconstitution system;
a specific ratio of beta-lactam antibiotic to beta-lactamase inhibitor.

The composition claim could therefore reach multiple dosage forms if the active compound satisfies the underlying compound limitation. It does not independently protect every sulbactam/durlobactam combination unless the relevant durlobactam compound is within Formula III.

What does the patent not expressly claim?

The supplied claims do not include an express method-of-treatment claim. They also do not expressly claim:

treatment of Acinetobacter baumannii;
treatment of hospital-acquired pneumonia;
treatment of ventilator-associated pneumonia;
administration with sulbactam;
a specific dosing regimen;
a specific manufacturing process;
a particular crystalline form;
a defined injectable formulation;
a kit or vial presentation.

Those subject areas may be covered by separate patents or regulatory exclusivity. They should not be assumed to fall within US 9,309,245 merely because the commercial product contains a claimed compound.

When does US 9,309,245 lose exclusivity?

The base patent term is expected to end on December 23, 2034, based on the earliest claimed nonprovisional priority date and the standard 20-year US patent term.[2]

Milestone	Date
Earliest claimed priority	December 23, 2013
US patent issue	April 12, 2016
Expected ordinary expiration	December 23, 2034
Xacduro FDA approval	May 23, 2023
Five-year NCE exclusivity, if applicable	May 23, 2028
QIDP-related exclusivity period	May 23, 2033, subject to FDA designation and regulatory calculation

The patent expiration date and FDA exclusivity dates are separate rights. FDA exclusivity can delay approval of an abbreviated application even after a particular patent challenge has been resolved. Conversely, patent expiry does not guarantee immediate generic entry if other listed patents or regulatory barriers remain.

Xacduro received Qualified Infectious Disease Product treatment, which can provide a five-year extension of applicable exclusivity under the Generating Antibiotic Incentives Now provisions. The regulatory exclusivity analysis must be performed against the approved NDA and FDA Orange Book records, not against the patent expiration date alone.[1,3]

What is the Orange Book status of Xacduro?

Xacduro is approved under NDA 217078 for injection of sulbactam and durlobactam. The FDA-approved labeling identifies durlobactam as a beta-lactamase inhibitor administered with sulbactam.[1]

The Orange Book analysis should distinguish four categories:

Category	Relevance
Drug substance patents	May protect durlobactam or related active ingredients
Drug product patents	May protect formulation, dosage form or composition
Method-of-use patents	May protect approved or narrower clinical uses
Regulatory exclusivity	May delay approval independent of patent validity

US 9,309,245 is primarily a drug-substance patent. It is not, on the supplied claim text, a narrow Xacduro formulation patent or an Acinetobacter treatment patent.

Orange Book listing and patent expiration should be checked against the current FDA publication because listed-patent status can change through corrections, delistings, patent-term adjustments or later patent submissions.[3]

Which companies are challenging US 9,309,245?

No Paragraph IV challenger can be identified from the claim text alone. A definitive current challenge analysis requires a review of:

FDA Paragraph IV certifications and litigation notices;
PACER and district court dockets;
Abbreviated New Drug Application activity;
Orange Book patent-listing updates;
any 30-month stay litigation involving Xacduro.

The commercial likelihood of a Paragraph IV filing is limited before the market supports a viable generic opportunity. Xacduro is an injectable hospital antibiotic product with a relatively specialized patient population. A challenger would need to address the active pharmaceutical ingredient, sterile manufacturing, drug-device or vial presentation, clinical labeling and any remaining listed patents.

What generic entry risks exist?

Generic entry risk is likely to develop in stages.

Early-entry scenario

A challenger could file an ANDA with a Paragraph IV certification before patent expiry. The likely theories would include:

non-infringement based on a different DBO substitution pattern;
invalidity for lack of written description across the broad Markush genus;
obviousness based on earlier DBO beta-lactamase inhibitor disclosures;
anticipation by a specific prior-art compound;
salt, stereochemistry or crystalline-form distinctions.

The broadest risk is concentrated in claim 1. Narrow species claims, including claims 6, 11, 14, 16, 17 and 18, may provide stronger positions if the commercial compound is directly recited or structurally encompassed by those claims.

Post-expiry entry

Absent a successful challenge or settlement, entry is principally constrained by the expected December 2034 patent expiration, subject to other patents and any patent-term adjustment. Regulatory exclusivity is expected to expire earlier than the base patent if the relevant NCE and QIDP periods apply.

Non-infringing design-around

A potential design-around could alter:

the 2S,5R stereochemistry;
the sulfate counterion or salt form;
R1 substitution;
R2 or R3 substitution;
the bridged-ring substitution pattern;
the lactam or sulfate functionality.

Not all such changes would avoid infringement. Doctrine-of-equivalents exposure, claim construction and prosecution-history estoppel would be material.

How strong is the patent estate?

The patent has several strengths:

It is a composition-of-matter patent covering the central DBO scaffold.
Claim 1 reaches a large substituent space.
The dependent claims provide multiple fallback positions.
The claims include specific sulfate and sodium-salt species.
Claim 19 adds a formulation-level claim for pharmaceutical compositions.

The principal vulnerabilities are:

Broad Markush claims may face written-description and enablement challenges.
DBO beta-lactamase inhibitor chemistry was an active prior-art field before the priority date.
The supplied claim text contains drafting irregularities in claim 15.
The missing chemical drawings for claims 2, 4, 7, 16 and 17 prevent complete scope analysis.
Later patents may be more commercially relevant to the marketed product than the foundational compound patent.

Overall, US 9,309,245 should be treated as a foundational active-ingredient patent with significant blocking potential for compounds that remain within the claimed 2S,5R sulfate DBO architecture. Its value is highest if the approved durlobactam structure falls within an issued species claim or a tightly drafted genus claim that survives validity review.

How does US 9,309,245 compare with competing beta-lactamase inhibitor patents?

Inhibitor	Core class	Commercial product	Principal competitive issue
Durlobactam	Diazabicyclooctane	Xacduro with sulbactam	Acinetobacter-focused activity and compound patent protection
Avibactam	Diazabicyclooctane	Avycaz, Zavicefta	Earlier broad DBO patent estate
Relebactam	Diazabicyclooctane	Recarbrio with imipenem/cilastatin	Combination and formulation protection
Vaborbactam	Cyclic boronate	Vabomere with meropenem	Different inhibitor scaffold and patent landscape
Taniborbactam	Cyclic boronate	Development-stage programs	Broad-spectrum beta-lactamase inhibition
Nacubactam	Diazabicyclooctane	Development-stage programs	Beta-lactamase inhibition and enhancer activity

US 9,309,245 is closer technically to avibactam and relebactam patents than to vaborbactam patents because all three use a diazabicyclooctane-related architecture. It remains distinct from patents directed to cyclic boronate inhibitors.

Does the patent create biosimilar risk?

No conventional biosimilar pathway applies. Durlobactam is a small-molecule drug, not a biologic. The relevant competitor pathway is an ANDA under section 505(j), a 505(b)(2) application, or, depending on the proposed product, a different NDA strategy.

The principal competitive barriers are therefore:

patent scope;
Orange Book listings;
FDA exclusivity;
sterile injectable manufacturing;
comparative pharmaceutical equivalence;
supply of the active ingredient;
hospital formulary adoption.

Key Takeaways

US 9,309,245 is a composition-of-matter patent for substituted 1,6-diazabicyclo[3.2.1]octane sulfate beta-lactamase inhibitors.
The patent contains a broad Markush claim, narrower formula claims, specific species claims and a pharmaceutical composition claim.
The claimed chemistry is directly relevant to durlobactam, the active inhibitor in Xacduro.
The expected ordinary patent expiration is December 23, 2034, subject to recorded patent-term adjustment.
FDA exclusivity for Xacduro may end before the patent, including potential NCE and QIDP periods.
The patent does not, based on the supplied claims, expressly claim a sulbactam combination, Acinetobacter treatment method or specific injectable formulation.
Generic entry would likely require a Paragraph IV strategy, a non-infringing formulation or a post-expiry launch.
A complete infringement opinion depends heavily on the omitted chemical drawings for claims 2, 4, 7, 16 and 17 and on the current Orange Book listing.

FAQs

Is US 9,309,245 a durlobactam patent?

It is a foundational patent covering the substituted diazabicyclooctane sulfate chemistry associated with durlobactam-type beta-lactamase inhibitors. Exact coverage of the FDA-approved durlobactam structure requires comparison with the complete issued claims and drawings.

Can a generic launch before December 2034?

Potentially, but only through a successful patent challenge, a non-infringing product, a settlement permitting earlier entry, or another legally available pathway. The patent expiration date alone does not determine launch timing.

Does the patent cover sulbactam-durlobactam as a combination?

The supplied claims primarily cover the inhibitor compound and pharmaceutical compositions containing it. They do not expressly recite sulbactam or a fixed sulbactam-to-durlobactam ratio.

Is durlobactam subject to biosimilar competition?

No. Durlobactam is a small molecule. Generic competition would generally proceed through an ANDA or another small-molecule approval pathway rather than a biosimilar application.

What is the largest validity risk for the patent?

The broadest validity risks are written description, enablement, obviousness and anticipation challenges directed to the Markush genus. Specific species claims may be more resilient if the commercial molecule is expressly disclosed and supported in the patent.

References

U.S. Food and Drug Administration. (2023). Xacduro (sulbactam and durlobactam) prescribing information.
U.S. Patent No. 9,309,245. (2016). Substituted 1,6-diazabicyclo[3.2.1]octane compounds. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

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	XACDURO (COPACKAGED)	durlobactam sodium; durlobactam sodium; sulbactam sodium	POWDER;INTRAVENOUS	216974-001	May 23, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial		Y			⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	090539	⤷ Start Trial
Australia	2013245399	⤷ Start Trial
Brazil	112014024279	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,309,245

Which drugs does patent 9,309,245 protect, and when does it expire?

Summary for Patent: 9,309,245