US Patent 10,933,053: Scope, Claim Construction, Exclusivity, and Ceftolozane/Tazobactam Patent Landscape

US Patent 10,933,053 protects a renal-dose regimen for ceftolozane/tazobactam in pneumonia patients with end-stage renal disease receiving hemodialysis. Its commercial target is the use of Zerbaxa, or an equivalent ceftolozane/tazobactam product, with a higher initial dose followed by lower maintenance doses.

The patent is a method-of-use patent, not a composition-of-matter patent. Its broadest claims require five core elements:

Pneumonia treatment.
A human patient with end-stage renal disease.
The patient is on hemodialysis.
A single loading dose is followed by maintenance doses.
Both loading and maintenance doses contain ceftolozane and tazobactam in a 2:1 active ratio, with the loading dose containing more active drug.

Claim 15 narrows the loading-to-maintenance relationship to a 5:1 ratio by weight. The dependent claims add intravenous administration, approximately eight-hour maintenance dosing, pharmacokinetic exposure targets, post-dialysis timing, salt forms, pneumonia subtypes, and specified pathogens.

What does US Patent 10,933,053 cover?

The patent covers a dosing method for ceftolozane/tazobactam in a narrowly defined renal population. The claim architecture is summarized below.

Claim group	Scope
Claims 1-14	Broad regimen using a larger loading dose and smaller maintenance doses
Claims 15-28	Same regimen, but loading dose is five times the maintenance dose by weight
Claims 29-31	Claim 1 regimen limited to nosocomial pneumonia and listed pathogens
Claims 32-34	Claim 15 regimen limited to nosocomial pneumonia and listed pathogens

The claims use “ceftolozane active” and “tazobactam active,” meaning the relevant comparison is based on active moieties rather than the gross weight of the salt or finished formulation. Claims 13, 14, 27, and 28 identify ceftolozane sulfate and tazobactam sodium as the relevant pharmaceutical salts.

What is the broadest enforceable concept?

Claim 1 is the principal broad claim. It does not require:

An exact 5:1 loading-to-maintenance ratio.
A specific gram amount.
Intravenous administration.
Administration within a specified time after hemodialysis.
Any particular bacterial pathogen.
The “nosocomial pneumonia” limitation.
The pharmacokinetic thresholds in claims 3-9.

A regimen can therefore fall within claim 1 even if the loading-to-maintenance ratio is greater than, or different from, 5:1, provided that:

The loading dose is larger than the maintenance dose for both active ingredients.
Both dose types retain the 2:1 ceftolozane-to-tazobactam active ratio.
The patient has end-stage renal disease and is receiving hemodialysis.
The indication is pneumonia.

The 5:1 ratio in claim 15 is a narrower but commercially important embodiment.

How does the claimed regimen compare with the FDA-approved Zerbaxa regimen?

The FDA-approved Zerbaxa labeling identifies a renal-adjusted regimen for patients with creatinine clearance of 15 to 29 mL/min and for patients with end-stage renal disease on hemodialysis. For hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, the labeled hemodialysis regimen uses a 2.25 g loading dose followed by 450 mg every eight hours, with dosing after hemodialysis as soon as possible when appropriate. The labeled loading dose is therefore five times the maintenance dose by weight: 2.25 g versus 0.45 g.[2]

Because the marketed product contains 1 g of ceftolozane and 0.5 g of tazobactam per 1.5 g vial, the labeled 2.25 g loading dose corresponds to 1.5 g of ceftolozane plus 0.75 g of tazobactam. The 450 mg maintenance dose corresponds to 300 mg of ceftolozane plus 150 mg of tazobactam. Both doses retain the 2:1 active ratio.

Regimen element	FDA-labeled HD pneumonia regimen	Patent claim relevance
Loading dose	2.25 g total product	Claims 1 and 15
Maintenance dose	450 mg total product	Claims 1 and 15
Loading-to-maintenance ratio	5:1	Claim 15
Ceftolozane:tazobactam active ratio	2:1	Claims 1 and 15
Maintenance interval	Every 8 hours	Claims 2 and 16
Route	Intravenous	Claims 2 and 16 imply the labeled administration method
Population	ESRD on hemodialysis	Claims 1 and 15
Disease	Hospital-acquired or ventilator-associated bacterial pneumonia	Claims 29 and 32 are narrower than the broad pneumonia claims
Post-dialysis dosing	As soon as possible after dialysis	Claims 10-12 and 24-26 narrow timing

The commercial overlap is high. A generic or alternative ceftolozane/tazobactam product used according to the FDA-approved renal dosing instructions could practice the central subject matter of claims 1 and 15.

What are the key claim limitations and infringement risks?

Patient population

The patient must have end-stage renal disease and be on hemodialysis. A patient with moderate or severe renal impairment who is not on hemodialysis would not satisfy this limitation.

The limitation is narrower than a general renal-impairment claim. It creates a meaningful design-around possibility for products used only in non-dialysis renal impairment, although such a product would not address the same clinical population.

Disease limitation

The independent claims require treatment of pneumonia. The patent does not claim all bacterial infections or all uses of ceftolozane/tazobactam.

Claims 29-34 narrow the indication to nosocomial pneumonia and specified organisms. These dependent claims create fallback positions but are less important where the accused regimen already satisfies the broader pneumonia claims.

Dose-ratio limitation

Both loading and maintenance doses must provide a 2:1 ratio of ceftolozane active to tazobactam active. Changing that ratio could avoid literal infringement, but a materially different ratio could affect the product's approved labeling, pharmacology, and regulatory substitutability.

Claim 15 adds a second requirement: the loading amount must be five times the maintenance amount for both actives. A product using a 4:1 or 6:1 relationship could avoid claim 15 while potentially remaining within claim 1 if the loading dose remains larger and all other limitations are met.

Loading-dose requirement

The claims require a single loading dose followed by maintenance doses. A regimen that begins directly with the maintenance dose may avoid the literal loading-dose limitation. This is a commercially difficult design-around because the loading dose addresses initial exposure in a patient whose drug clearance is altered by renal failure and dialysis.

Administration interval

Claims 2 and 16 specify intravenous maintenance dosing about every eight hours. The independent claims do not require the eight-hour interval. A dosing schedule every 12 hours could avoid those dependent claims but would not necessarily avoid claims 1 or 15.

Post-hemodialysis timing

Claims 10-12 and 24-26 cover administration of the first maintenance dose within three, two, or one hour after completion of hemodialysis. These claims are nested timing claims. They do not expand the independent claim scope because claims 1 and 15 do not require a particular post-dialysis interval.

The timing limitations may be relevant to hospital protocols and electronic medication orders. A label instructing administration “as soon as possible” after dialysis could create practical infringement exposure if the actual administration routinely occurs within the claimed windows.

What do the pharmacokinetic claims protect?

Claims 3-9 and 17-23 define exposure-based regimens. They require specified unbound concentrations over time and, in claims 9 and 23, a daily ceftolozane AUC below 1,100 microgram-hours per milliliter.

Claim limitation	Threshold
Unbound ceftolozane exposure	At least 8 micrograms/mL for at least 30% of the relevant interval
Alternative ceftolozane exposure	At least 8 micrograms/mL for at least 40% of the relevant interval
Unbound tazobactam exposure	At least 1 microgram/mL for at least 20%
Alternative tazobactam exposure	At least 0.5 micrograms/mL for at least 50%
Daily ceftolozane AUC	Less than 1,100 microgram-hours/mL

These limitations create two legal issues.

First, infringement may depend on patient-specific pharmacokinetics. The same administered dose may produce different unbound concentrations depending on body weight, residual renal function, dialysis duration, dialysis membrane, albumin concentration, infection severity, and sampling methodology.

Second, the claims use the phrase “between successive treatment days,” which may require construction from the specification and prosecution history. That phrase is less precise than a conventional dosing interval and could generate disputes over the relevant time window, especially when dialysis interrupts the dosing schedule.

How strong is the patent estate for this regimen?

The patent is commercially relevant but narrower and more vulnerable than a composition patent.

Strengths

It maps closely to the FDA-approved hemodialysis regimen.
It covers the high-value ESRD population in which dose selection is clinically constrained.
Claim 1 does not require the exact 5:1 ratio used in the label.
Claim 15 captures the labeled 2.25 g-to-450 mg regimen.
The claims include multiple fallback limitations for interval, exposure, salts, timing, disease, and pathogens.
The claimed dosing architecture is difficult to avoid while maintaining the same labeled regimen.

Weaknesses

The claims are limited to pneumonia rather than all indications.
They apply only to patients with end-stage renal disease on hemodialysis.
The claims require a loading dose followed by maintenance dosing.
Some dependent claims depend on pharmacokinetic facts that may be difficult to prove reliably in an individual patient.
The patent does not prevent manufacture of ceftolozane, tazobactam, or the combination outside the claimed method.
A product label that omits the patented use may reduce induced-infringement exposure, although actual marketing, promotional conduct, and prescribing evidence remain relevant under 35 U.S.C. §271(b).

The strongest commercial claims are claims 1 and 15. Claims 2 and 16 may be important where the label expressly states every-eight-hour dosing. Claims 10-12 and 24-26 are narrower operational claims. Claims 3-9 and 17-23 may provide additional protection but are more dependent on pharmacokinetic proof.

What patent landscape surrounds ceftolozane/tazobactam?

Ceftolozane/tazobactam, marketed as Zerbaxa by Merck following Merck's acquisition of Cubist, has a layered patent landscape.

Composition and active-ingredient patents

Earlier patents cover ceftolozane, tazobactam combinations, pharmaceutical compositions, and related beta-lactam formulations. These patents are distinct from US 10,933,053 because the patent at issue claims a patient-specific dosing method.

Composition patents generally create broader manufacturing and product barriers. The '053 patent is narrower but can remain relevant after composition claims expire if the approved labeling continues to direct the claimed regimen.

Formulation and salt protection

The claims expressly identify ceftolozane sulfate and tazobactam sodium. The patent does not, based on the supplied claims, claim a new crystalline form, excipient system, vial configuration, reconstitution process, or stability profile.

Accordingly, its formulation relevance is indirect. A competing product using different pharmaceutically acceptable salts could still infringe claims 1, 2, 3, 15, or other claims that do not require the specific salt limitations.

Method-of-use protection

US 10,933,053 is principally a method-of-use patent for renal-adjusted pneumonia treatment. Its scope is narrower than a patent covering all ceftolozane/tazobactam use in hospital-acquired pneumonia, but its dosing limitations align closely with the clinically relevant hemodialysis regimen.

Manufacturing and process barriers

The supplied claims do not cover:

Fermentation of ceftolozane.
Chemical synthesis of tazobactam.
Purification.
Sterile filling.
Lyophilization.
Vial packaging.
Reconstitution.
Stability testing.

A manufacturer could therefore face no direct infringement under these claims merely by making or selling the active ingredients. The risk arises when the product is supplied with instructions or promotion that lead to the claimed use.

What is the Orange Book status of US Patent 10,933,053?

The FDA Orange Book identifies patents submitted by an NDA holder for an approved drug. A patent can be technically relevant to an approved regimen without being listed in the Orange Book. Orange Book listing status must be determined from the current FDA patent listing for NDA 206829, the Zerbaxa NDA.[1]

US 10,933,053 should be analyzed as a potential method-of-use listing rather than as a product or formulation listing. If listed with a use code covering ceftolozane/tazobactam dosing in ESRD patients on hemodialysis, an ANDA applicant may face a Paragraph IV certification or a section viii statement, depending on the proposed labeling.

The claims are not directed to the active ingredient itself. A generic applicant that seeks approval for the same labeled hemodialysis pneumonia regimen would face greater risk than an applicant that carves out the patented use from its labeling.

When does US Patent 10,933,053 lose exclusivity?

The claims supplied do not establish the patent's earliest effective filing date, patent-term-adjustment period, terminal disclaimer, or any patent-term extension. Those items control the legally operative expiration date.

The ordinary rule is that a United States utility patent expires 20 years from the earliest effective nonprovisional application filing date, subject to patent-term adjustment, terminal disclaimers, and other statutory adjustments.[3] The patent's front-page bibliographic data and USPTO Patent Center record control the expiration calculation.[4]

The patent should not be treated as expiring merely on the 20-year anniversary of the date shown in a continuation or divisional filing. The earliest priority chain must be reviewed.

Which companies are challenging the patent?

The supplied claim text does not identify any Paragraph IV notice letter, ANDA applicant, district-court action, inter partes review, post-grant review, or settlement involving US 10,933,053.

A definitive challenger analysis requires review of:

FDA Paragraph IV litigation records.
District court dockets under 35 U.S.C. §271(e)(2).
USPTO Patent Center.
PTAB trial records.
Orange Book patent-listing history.
Any settlement or license filed in the Federal Trade Commission's pharmaceutical settlement database.

No challenger or settlement should be attributed to the patent without a docket or regulatory record.

What generic entry scenarios exist?

Scenario 1: Same labeled regimen

A generic applicant seeking the same 2.25 g loading dose followed by 450 mg every eight hours in hemodialysis patients would face the highest risk. The regimen appears to satisfy the central limitations of claims 1 and 15, assuming the applicant's label identifies pneumonia treatment.

Scenario 2: Section viii labeling carve-out

A generic applicant could attempt to omit the patented hemodialysis pneumonia use from its labeling. The commercial value of this strategy depends on whether the omitted use is separable from the remaining approved indications and whether the FDA accepts the proposed carve-out.

Scenario 3: Alternative dose ratio

Changing the loading-to-maintenance ratio could avoid claim 15. It may not avoid claim 1, which requires only that both loading amounts exceed the corresponding maintenance amounts.

Scenario 4: No loading dose

A regimen without a single loading dose could avoid the principal claims, but the approach would need to remain clinically and regulatorily acceptable.

Scenario 5: Different patient population

Use in patients with renal impairment who are not on hemodialysis would not satisfy the express ESRD-on-hemodialysis limitation.

What litigation and validity issues are most material?

The principal validity and enforcement issues are likely to involve:

Written description and enablement for the full range of ratios, concentrations, exposure percentages, and post-dialysis timing.
Definiteness of “about every 8 hours.”
Definiteness and construction of “between successive treatment days.”
Whether “pneumonia” requires a diagnosed bacterial infection or includes empiric treatment.
Whether active-moiety ratios are measured by mass, molar amount, or label-defined equivalent.
Obviousness based on the known need to adjust beta-lactam dosing in dialysis patients.
Obviousness of combining the FDA-approved renal dose with a loading-dose strategy.
Inherency of the pharmacokinetic exposure limitations.
Written-description support for the exact 5:1 ratio in claim 15.

The patent's strongest litigation position is likely against a product that copies the FDA-labeled regimen. Its weaker position is against a product with a materially different label, no loading dose, no pneumonia indication, or no dialysis-specific instructions.

Key Takeaways

US 10,933,053 is a renal-dose method patent for ceftolozane/tazobactam in pneumonia patients with ESRD receiving hemodialysis.
Claims 1 and 15 are the commercial center of the patent.
Claim 15 directly covers a 5:1 loading-to-maintenance ratio, corresponding to the labeled 2.25 g loading dose and 450 mg maintenance dose.
The patent does not claim the ceftolozane/tazobactam molecule, general product composition, manufacturing process, or all pneumonia uses.
The greatest generic risk arises from an ANDA label that reproduces the hemodialysis pneumonia regimen.
A section viii carve-out, omission of the loading dose, alternative patient population, or different dosing ratio may reduce infringement risk.
The pharmacokinetic claims provide fallback coverage but create proof and claim-construction issues.
The legally controlling expiration date requires review of the complete priority chain, patent-term adjustment, and any terminal disclaimer.
Orange Book listing and Paragraph IV exposure must be confirmed against the current FDA NDA and patent records.

FAQs

Does US 10,933,053 cover Zerbaxa for all renal-impaired patients?

No. The supplied claims require end-stage renal disease and hemodialysis. They do not cover every patient with reduced renal function.

Does changing the ceftolozane/tazobactam ratio avoid the patent?

It may avoid the 2:1 limitation, but the regulatory and clinical consequences could be material. Changing only the loading-to-maintenance ratio may avoid claim 15 while leaving claim 1 potentially applicable.

Does the patent cover a ceftolozane/tazobactam vial?

Not based on the supplied claims. The claims cover administering the drugs in a specified treatment regimen, not the vial as a product.

Can a generic omit the patented dialysis regimen from its label?

A generic applicant may seek a section viii labeling carve-out where the patented use is legally separable from the approved uses. FDA acceptance and infringement risk depend on the proposed label and actual marketing conduct.

Are the pathogen claims necessary to infringe the patent?

No. Claims 29-34 require specific pneumonia categories or organisms. Claims 1 and 15 are broader and do not require a listed pathogen.

References

U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Zerbaxa (ceftolozane and tazobactam) prescribing information. Merck Sharp & Dohme LLC.
United States Code. (2024). 35 U.S.C. §154: Contents and term of patent; provisional rights.
United States Patent and Trademark Office. (n.d.). Patent Center.
United States Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, §2710: Patent term adjustment.
U.S. Patent No. 10,933,053. (2021). United States Patent and Trademark Office.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cubist Pharms Llc	ZERBAXA	ceftolozane sulfate; tazobactam sodium	POWDER;INTRAVENOUS	206829-001	Dec 19, 2014		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
Australia	2014233637	⤷ Start Trial
Australia	2016202199	⤷ Start Trial
Australia	2017279686	⤷ Start Trial
Australia	2020202756	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,933,053