United States Patent 9,381,200: Claim Scope, Patent Landscape, and Generic Entry Risk

US Patent No. 9,381,200 covers antibacterial combinations containing cefepime and one of two structurally defined diazabicyclooctane beta-lactamase inhibitors. The claims also cover combinations with sulbactam and methods of treating bacterial infections or increasing cefepime’s antibacterial effectiveness. The patent is a combination and method-of-use patent, not a broad claim to cefepime, sulbactam, or the inhibitor chemical class generally.[1]

What does US Patent 9,381,200 protect?

The patent protects four principal subject-matter categories:

Claim category	Claims	Protected subject matter
Cefepime plus piperidine-substituted inhibitor	1	Pharmaceutical composition
Cefepime plus pyrrolidine-substituted inhibitor	2	Pharmaceutical composition
Cefepime, inhibitor, and sulbactam	3-4	Three-component pharmaceutical composition
Treatment and potentiation methods	5-9	Administration for bacterial infection or increased cefepime effectiveness

The two claimed inhibitors are defined by lengthy chemical names rather than common nonproprietary names. One contains an R-piperidine-3-carbonyl substituent. The other contains an R-pyrrolidine-3-carbonyl substituent. Each is attached to a 7-oxo-1,6-diazabicyclo[3.2.1]octane core bearing a sulfuric acid monoester group.

The independent composition claims require both:

Cefepime or a pharmaceutically acceptable derivative; and
The specified piperidine or pyrrolidine diazabicyclooctane inhibitor, including a stereoisomer or pharmaceutically acceptable salt.

A product containing cefepime alone does not fall within claims 1 or 2. A product containing the inhibitor alone does not fall within those claims. Infringement requires the claimed combination or a method of administering the claimed combination.

How narrow are claims 1 and 2?

Claims 1 and 2 are chemically narrow but commercially important. Each is limited to a single defined inhibitor structure and its permitted stereoisomers and salts.

Claim 1: cefepime plus the piperidine derivative

Claim 1 requires cefepime together with the inhibitor containing an R-piperidine-3-carbonyl group. A competing inhibitor with a different ring size, different stereochemistry, or a materially different side chain would not literally satisfy the claim unless the altered structure still falls within the claim’s interpretation of a stereoisomer, derivative, or salt.

The claim does not require:

A specific cefepime-to-inhibitor ratio;
A particular dosage;
A particular route of administration;
A fixed-dose formulation;
A specific bacterial species;
A specific clinical indication; or
A particular pharmaceutical excipient.

The absence of ratio and formulation limitations gives claim 1 potentially broad product coverage once the claimed inhibitor and cefepime are present in the same pharmaceutical composition.

Claim 2: cefepime plus the pyrrolidine derivative

Claim 2 has the same basic architecture but requires the R-pyrrolidine-3-carbonyl inhibitor. The pyrrolidine and piperidine compounds are separate claimed species. A product using the pyrrolidine compound does not satisfy claim 1 merely because the two inhibitors share the same diazabicyclooctane core.

The distinction between piperidine and pyrrolidine is commercially relevant. A development program could avoid one claim by selecting the other compound, but claims 1 and 2 together close that straightforward substitution path for the two named species.

What do claims 3 and 4 add for sulbactam combinations?

Claims 3 and 4 depend on claims 1 and 2 and add sulbactam or a pharmaceutically acceptable salt.

Claim	Required combination
3	Cefepime + piperidine inhibitor + sulbactam
4	Cefepime + pyrrolidine inhibitor + sulbactam

These claims are narrower than claims 1 and 2 because they require a third active component. They may become relevant to a triple-beta-lactamase-inhibitor product or a co-formulated regimen containing cefepime, the claimed diazabicyclooctane inhibitor, and sulbactam.

Sulbactam is not required for infringement of claims 1 or 2. Conversely, a cefepime product containing the claimed inhibitor but no sulbactam can still implicate claims 1 and 2.

What do claims 5 through 9 cover?

Claims 5 through 9 are method claims.

Claims 5-7: treatment of bacterial infection

Claim 5 covers administration of a composition according to claims 1 through 4. Claims 6 and 7 separately cover administration of cefepime with either the piperidine or pyrrolidine inhibitor in a pharmaceutically effective amount.

The method claims are not limited to a particular bacterial pathogen or disease site. On their face, they extend to treatment of bacterial infection generally, subject to ordinary claim-construction requirements concerning the composition, active ingredients, and effective amount.

Claims 6 and 7 may be more difficult to enforce against a manufacturer that sells the components separately. They are directed to administering both active agents, not merely manufacturing or selling cefepime. Enforcement would depend on the conduct of the relevant parties and evidence of intended combination use.

Claims 8 and 9: increased cefepime effectiveness

Claims 8 and 9 cover co-administering cefepime with one of the two claimed inhibitors for the purpose of increasing cefepime’s antibacterial effectiveness.

These claims are functionally framed. They do not state a required percentage increase in activity, minimum pharmacodynamic endpoint, or defined susceptibility threshold. The absence of a quantified efficacy threshold may support broad coverage, but it may also create issues concerning claim construction, enablement, written description, and proof that the claimed effectiveness increase occurred.

How does the claim set overlap?

The claims create overlapping protection around two inhibitor species:

Product or use	Claim exposure
Cefepime + piperidine inhibitor	Claims 1, 5, 6, and 8
Cefepime + pyrrolidine inhibitor	Claims 2, 5, 7, and 9
Cefepime + piperidine inhibitor + sulbactam	Claims 1, 3, 5, 6, and 8
Cefepime + pyrrolidine inhibitor + sulbactam	Claims 2, 4, 5, 7, and 9
Cefepime alone	Outside the supplied claims
Sulbactam plus cefepime without either claimed inhibitor	Outside the supplied claims
Claimed inhibitor without cefepime	Outside the composition claims

The practical effect is a layered claim structure. The core commercial combination is protected by claims 1 and 2. Treatment use is separately protected by claims 5 through 9. Sulbactam creates narrower fallback positions in claims 3 and 4.

Does the patent claim cefepime itself?

No. The claims use cefepime as one component of a combination. They do not claim cefepime as a compound, cefepime monotherapy, cefepime manufacturing, or all cefepime beta-lactamase-inhibitor combinations.

The phrase “cefepime or a pharmaceutically acceptable derivative thereof” broadens the cefepime component beyond a single salt or presentation. It does not eliminate the requirement that the product contain the claimed diazabicyclooctane inhibitor.

What formulations are protected by US 9,381,200?

The supplied claims do not require a particular formulation type. Potentially relevant products include:

Injectable solutions;
Injectable powders for reconstitution;
Co-packaged cefepime and inhibitor products;
Fixed-dose combination products;
Separate-vial regimens administered together; and
Formulations containing sulbactam in addition to cefepime and the claimed inhibitor.

The claims do not expressly require that cefepime and the inhibitor be physically mixed in one vial. Claim 1 refers to a pharmaceutical composition, while claims 6 through 9 refer to administering or co-administering the agents. A dual-vial kit could raise different issues from a single-vial formulation, particularly under the method claims.

A formulation containing only an unrelated excipient, stabilizer, buffer, or carrier would not avoid the claims if all required active ingredients remain present.

What manufacturing and intellectual-property barriers exist?

The patent does not claim a manufacturing process for either inhibitor based on the supplied claims. It therefore does not directly block synthesis of the compounds when they are not made, sold, or used in a claimed cefepime combination.

Commercial barriers may still arise from:

Separate composition-of-matter patents covering the inhibitor;
Process patents covering key intermediates;
Crystalline or salt-form patents;
Formulation and stability patents;
Regulatory exclusivity for an approved combination;
Trade secrets involving synthesis or impurity control; and
Patents covering dosage, infusion duration, or treatment of resistant pathogens.

A freedom-to-operate review limited to US 9,381,200 would therefore be incomplete for a developer intending to commercialize either inhibitor.

When does US Patent 9,381,200 lose exclusivity?

US 9,381,200 was issued on July 5, 2016. US utility patents generally expire 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and continuity information.[2]

The issue date alone does not establish the legally operative expiration date. The patent’s front-page term information, continuity chain, and USPTO Patent Term Adjustment calculation control the final date. The supplied claim text does not contain that information.

Patent-term extension under 35 U.S.C. §156 could become relevant only if the patent claims a product or method eligible for extension and the statutory requirements are met. Patent-term adjustment under 35 U.S.C. §154(b) may also affect the date.[2]

What is the Orange Book status?

The supplied patent claims are not enough to establish an Orange Book listing. The FDA Orange Book lists patents submitted for approved drug products, generally including drug substance, drug product, and method-of-use patents that meet FDA listing requirements.[3]

The key regulatory distinction is:

Question	Assessment from the supplied claims
Does the patent claim cefepime alone?	No
Does it claim a cefepime combination?	Yes
Is an Orange Book listing established by the claim text?	No
Would a listing depend on an approved NDA product?	Yes
Would Paragraph IV litigation require an applicable listed patent?	Generally yes

Cefepime itself is widely available as a generic cephalosporin. That does not resolve patent risk for a new cefepime-plus-inhibitor product. If a combination drug covered by the patent received FDA approval and the patent were properly listed, an ANDA applicant could face a Paragraph IV certification and associated litigation under the Hatch-Waxman framework.[4]

Are there Paragraph IV challenges or patent litigation?

The claim text does not establish a Paragraph IV challenge, ANDA filing, district-court action, or settlement involving US 9,381,200. Paragraph IV activity is product-specific and depends on an approved reference drug, an Orange Book listing, and an ANDA certification.[4]

For a combination involving an unapproved investigational diazabicyclooctane inhibitor, the more immediate risk is pre-launch patent litigation under the Hatch-Waxman system only after an NDA product and listed patent exist. Before that point, disputes may arise through:

Declaratory-judgment actions;
Patent-validity challenges;
Licensing negotiations;
Inter partes review;
Patent-opposition or post-grant proceedings where available; and
Commercial launch disputes involving separate component sales.

No settlement terms should be inferred from the existence of the patent alone.

How strong is the patent estate?

The supplied patent has moderate claim breadth at the combination level and limited breadth at the chemical level.

Strength factor	Assessment
Chemical scope	Narrow; two specifically defined inhibitor species
Combination scope	Broad as to ratio, route, and formulation, subject to the “composition” limitation
Method scope	Broad in disease and pathogen language
Sulbactam fallback	Narrower but potentially useful
Manufacturing coverage	Not present in the supplied claims
Cefepime coverage	Combination-only
Design-around potential	Meaningful if a different inhibitor is used
Proof burden	Higher for functional effectiveness claims 8 and 9

The strongest commercial claims are likely claims 1 and 2 if a product contains cefepime and one of the named inhibitors. Claims 5 through 7 provide additional method coverage. Claims 8 and 9 may be valuable in clinical-use contexts but could require more evidence concerning the claimed increase in cefepime effectiveness.

Potential validity pressure points include:

Written-description support for the full stereoisomer and salt language;
Enablement across the claimed combination scope;
Obviousness based on cefepime and known beta-lactamase inhibitors;
Unexpected synergy or potentiation evidence;
Definiteness of the chemical nomenclature; and
The scope of “pharmaceutically acceptable derivative” and “stereoisomer.”

What generic launch scenarios exist?

Launch of cefepime alone

A generic cefepime manufacturer is not within the supplied combination claims when selling cefepime without either claimed inhibitor. US 9,381,200 therefore does not block ordinary cefepime generic entry.

Launch of cefepime with a different inhibitor

A different beta-lactamase inhibitor could avoid literal infringement if it does not fall within the claimed chemical definitions. Other patents covering the substitute inhibitor would then become central.

Launch using the piperidine or pyrrolidine inhibitor

A product combining cefepime with either named inhibitor presents direct risk under claims 1 or 2, with additional exposure under the corresponding method claims.

Separate-component launch

Selling cefepime and the inhibitor as separate products may reduce composition-claim exposure in some circumstances, but it does not automatically eliminate method-claim risk. Labeling, promotional materials, dosing instructions, distribution structure, and evidence of intended co-administration would be material.

Triple combination with sulbactam

A cefepime-plus-inhibitor-plus-sulbactam product implicates claims 3 and 4 as well as the broader underlying claims 1 and 2.

How does this patent compare with the broader beta-lactamase-inhibitor landscape?

US 9,381,200 should be analyzed as one layer in a larger beta-lactamase-inhibitor portfolio.

Avibactam and ceftazidime-avibactam

Avibactam is a diazabicyclooctane beta-lactamase inhibitor used commercially with ceftazidime. Its patent estate is distinct from the specific piperidine and pyrrolidine inhibitors claimed here. Ceftazidime-avibactam patents and regulatory exclusivities do not automatically protect cefepime combinations.[5]

Relebactam and imipenem-cilastatin-relebactam

Relebactam is another diazabicyclooctane inhibitor, but its chemical structure and combination claims differ. Relebactam-related patents are not interchangeable with the claims of US 9,381,200.[6]

Vaborbactam and meropenem-vaborbactam

Vaborbactam is a cyclic boronate rather than the diazabicyclooctane structure described in the supplied claims. Its combination and method patents form a separate estate.[7]

Cefepime-zidebactam and other investigational combinations

Cefepime combinations with newer beta-lactamase inhibitors may create overlapping commercial objectives without falling within US 9,381,200. The decisive issue is whether the product uses one of the two claimed inhibitor structures, not whether it is generally characterized as a cefepime beta-lactamase-inhibitor combination.

What licensing and commercial issues are relevant?

The patent’s value depends on control of the claimed inhibitor compounds and the ability to develop an approved cefepime combination. A license covering US 9,381,200 alone may not provide freedom to commercialize the inhibitor if separate composition-of-matter or process patents remain in force.

A commercial license should address:

The patent family and foreign counterparts;
Composition-of-matter and process patents;
Regulatory submissions and Orange Book rights;
Field of use;
Combination products and co-packaged products;
Sublicensing rights;
Patent prosecution control;
Enforcement responsibility;
Paragraph IV litigation allocation;
Royalty treatment for separate-component sales; and
Rights after patent expiration or invalidation.

Key Takeaways

US 9,381,200 covers cefepime combined with two specifically defined diazabicyclooctane beta-lactamase inhibitors.
Claims 1 and 2 are the central composition claims.
Claims 3 and 4 add sulbactam and are narrower fallback claims.
Claims 5 through 9 cover treatment of bacterial infection and increased cefepime effectiveness.
The patent does not claim cefepime alone, sulbactam alone, or a manufacturing process based on the supplied claims.
A cefepime product using a different beta-lactamase inhibitor may avoid literal infringement of the supplied claims, subject to other patents.
Separate-component sales do not automatically eliminate method-claim risk.
The patent’s exact expiration date requires the USPTO term calculation and continuity record.
No Orange Book listing, Paragraph IV challenge, litigation, or settlement can be established from the claim text alone.
A complete freedom-to-operate analysis must include the inhibitor’s composition-of-matter, process, salt, formulation, and regulatory patent families.

FAQs

Does US 9,381,200 block generic cefepime?

No. The supplied claims require cefepime together with one of two specifically defined inhibitors, or a method involving that combination.

Can a company avoid the patent by using avibactam?

Possibly at the level of the supplied claims, because avibactam is a different inhibitor structure. Avibactam-related patents and regulatory protections require separate analysis.

Does adding sulbactam create a new patent problem?

Yes. A triple combination containing cefepime, one claimed inhibitor, and sulbactam can implicate claims 3 and 4 in addition to the broader combination claims.

Are the piperidine and pyrrolidine inhibitors interchangeable for infringement purposes?

No. They are separately recited chemical species. A product using the piperidine compound implicates a different claim path from a product using the pyrrolidine compound.

Is an FDA-approved product required before Paragraph IV litigation can occur?

A conventional Paragraph IV case generally requires an ANDA applicant, an applicable reference-listed drug, and a patent listed in the FDA Orange Book. The patent number alone does not establish those conditions.

References

United States Patent and Trademark Office. (2016). U.S. Patent No. 9,381,200, pharmaceutical compositions comprising cefepime and beta-lactamase inhibitors.
United States Code, 35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
United States Code, 21 U.S.C. § 355(j); 35 U.S.C. § 271(e).
U.S. Food and Drug Administration. (2015). Avycaz (ceftazidime and avibactam) prescribing information.
U.S. Food and Drug Administration. (2019). Recarbrio (imipenem, cilastatin, and relebactam) prescribing information.
U.S. Food and Drug Administration. (2017). Vabomere (meropenem and vaborbactam) prescribing information.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Wockhardt Bio Ag	ZAYNICH	cefepime hydrochloride; zidebactam	POWDER;INTRAVENOUS	220787-001	May 29, 2026		RX	Yes	Yes	9,381,200	⤷ 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
Australia	2012303691	⤷ Start Trial
Brazil	112013028813	⤷ Start Trial
Canada	2833241	⤷ Start Trial
China	103619843	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,381,200