Details for Patent: 10,376,496
Which drugs does patent 10,376,496 protect, and when does it expire?
Patent 10,376,496 protects ZERBAXA and is included in one NDA.
Protection for ZERBAXA has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.
This patent has seven patent family members in four countries.
Summary for Patent: 10,376,496
| Title: | Treating infections with ceftolozane/tazobactam in subjects having impaired renal function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Disclosed are methods of administering cephalosporin/tazobactam to human patients with end stage renal disease undergoing hemodialysis and suffering from a complicated intra-abdominal infection or a complicated urinary tract infection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Gopal Krishna, Gurudatt Chandorkar, Elham Hershberger, Benjamin Miller, Alan Xiao | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Cubist Pharmaceuticals LLC , Merck Sharp and Dohme LLC , Calixa Therapeutics Inc | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US14/481,496 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Patent Claim Types: see list of patent claims | Use; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 10,376,496: Ceftolozane-Tazobactam Patent Scope, Expiration, Orange Book Status, and Generic Entry RiskUS Patent No. 10,376,496 protects a renal-dose treatment method for Zerbaxa, the ceftolozane-tazobactam combination, in patients with end-stage renal disease receiving hemodialysis. The patent is narrower than a composition-of-matter patent but commercially relevant because it covers the labeled intravenous dosing regimen for hemodialysis patients with complicated intra-abdominal infection and complicated urinary tract infection. The core protected regimen is:
The patent does not broadly cover all uses of ceftolozane-tazobactam. It targets a defined patient population, infection category, microorganism profile, dose sequence and administration schedule. A generic product could potentially avoid literal infringement by using a materially different renal dosing regimen, although regulatory and induced-infringement risks would remain. What does US Patent 10,376,496 cover?US 10,376,496 is a method-of-treatment patent directed to administering ceftolozane-tazobactam to hemodialysis patients with severe renal impairment. The patent claims do not primarily protect the chemical compounds themselves. They protect the clinical use and dosing protocol. Independent claim 1Claim 1 contains multiple cumulative limitations. A successful infringement analysis would need to establish each material element:
The claim requires both the loading dose and the subsequent maintenance dosing. Administration of only the maintenance dose would not satisfy the complete literal scope of claim 1. The active-ingredient language also matters. The claimed amounts are expressed as ceftolozane active and tazobactam active, rather than the gross weight of the salt or finished drug product. This prevents a manufacturer from avoiding the dose limitation merely by using a different salt form. Pathogen limitationsClaim 1 separately identifies microorganisms associated with cIAI and cUTI. For cIAI, the listed organisms include:
For cUTI, the listed organisms include:
The pathogen limitation could create proof issues in litigation. A plaintiff would need evidence that the infection was caused by at least one listed organism. The limitation may be satisfied by microbiology results, clinical records, or prescribing information, depending on the factual record and claim construction. How do the dependent claims narrow the patent scope?Claims 2 through 14 add narrower versions of the regimen in claim 1.
Claims 7 and 8 are particularly important because they address post-hemodialysis dosing. Claim 8 is narrower than claim 7. A dose administered within two hours after dialysis necessarily falls within the three-hour period, assuming all other claim elements are met. What is the commercial significance of the renal dosing claims?The claims align closely with the FDA-approved renal dosing instructions for Zerbaxa in patients receiving hemodialysis. The Zerbaxa prescribing information directs a 500 mg/250 mg loading dose followed by a 100 mg/50 mg dose every eight hours for cIAI and cUTI patients with end-stage renal disease on hemodialysis. It also addresses administration after hemodialysis.[2] That alignment increases the practical relevance of the patent. A generic applicant seeking approval for the same renal dosing regimen could face a Paragraph IV challenge or a section viii labeling strategy issue, depending on the Orange Book listing and the proposed labeling. The claims remain narrower than the full FDA label because they include specific pathogen lists and, in some claims, a defined one-hour infusion or post-dialysis timing limitation. When does US Patent 10,376,496 expire?The expected statutory expiration date is June 6, 2034, subject to any applicable patent-term adjustment, patent-term extension, terminal disclaimer or other adjustment reflected in the USPTO and FDA records.[1][3]
The June 6, 2034 date should be treated as the operative expected expiration date rather than an absolute launch date. Generic entry can occur before expiration through litigation settlement, a successful validity or infringement decision, or a licensed launch agreement. What is the Orange Book status of US 10,376,496?US 10,376,496 has been associated with Zerbaxa patent protection and is relevant to FDA-approved dosing in renally impaired patients. The FDA Orange Book is the controlling source for current listing status, use codes, patent expiration information and certifications associated with the approved NDA.[4] The patent’s regulatory significance is likely concentrated in the labeled dosing regimen for:
An Orange Book-listed method-of-use patent generally requires an ANDA applicant to address the patent through a Paragraph III certification, Paragraph IV certification or, where legally available, a section viii statement that omits the patented method from labeling.[5] The feasibility of a section viii strategy depends on the exact use code and whether the proposed generic labeling can omit the patented renal regimen while retaining an approvable label. If the FDA-approved dosing information for hemodialysis patients is necessary for safe use, omission may be difficult. What Paragraph IV challenges and generic entry risks exist?A generic applicant could challenge US 10,376,496 on several grounds:
The strongest noninfringement route would be to avoid the claimed regimen in labeling. That strategy carries regulatory risk because renal dosing instructions are central to safe administration in end-stage renal disease. A generic applicant that promotes or induces use of the patented dose sequence could face induced-infringement allegations even if its product label is carefully drafted. How strong is the patent estate for Zerbaxa?US 10,376,496 is one component of a broader Zerbaxa intellectual-property estate. The estate can include:
The strength of US 10,376,496 is highest against a product that reproduces the exact FDA renal regimen. Its strength is lower against a product that avoids the claimed pathogen limitation, changes the administration schedule, removes the hemodialysis-specific method from labeling, or relies on a different approved indication. The patent does not block all generic ceftolozane-tazobactam products after expiration of other patents. Its commercial value depends on whether competing applicants need to market the covered hemodialysis dosing instructions. What formulations are protected by US 10,376,496?The patent does not broadly claim every Zerbaxa formulation. Claims 6 and 9 through 14 require ceftolozane sulfate and tazobactam sodium. The claims therefore protect administration of the active ingredients in those salt forms when combined with the claimed patient, infection and dosing limitations. The formulation limitation is narrower than a conventional formulation patent. It does not necessarily protect:
A competing formulation using different salt forms could still face infringement exposure if the doctrine of equivalents applies, but literal infringement would require the claimed salt forms in the relevant dependent claim. What manufacturing and intellectual-property barriers affect generic entry?A generic manufacturer must address more than the renal-dose patent. Key barriers include:
Ceftolozane-tazobactam is an injectable antibacterial combination. Sterile manufacturing and quality-control requirements can delay commercial entry even after patent litigation is resolved. What litigation or settlement agreements affect the patent?US 10,376,496 was issued in 2019. A complete current assessment of active litigation, Paragraph IV notices, consent judgments and settlement agreements requires the current district-court docket, FDA Orange Book data and USPTO records. The principal litigation trigger would be an ANDA applicant certifying that the patent is invalid, unenforceable or not infringed. A Paragraph IV notice would give the NDA holder a 45-day period to file an infringement action, potentially triggering a 30-month FDA approval stay under the Hatch-Waxman framework.[5] Merck obtained Zerbaxa through its acquisition of Cubist Pharmaceuticals, completed in 2015. The transaction transferred Cubist’s commercial and patent interests in the product to Merck.[6] No separate license is required to explain Merck’s current position as the product sponsor and patent-interest holder. How does US 10,376,496 compare with broader Zerbaxa patents?
US 10,376,496 is narrower than a composition patent but may be more directly relevant to an ANDA label because it tracks a specific FDA-approved renal dosing regimen. Its value is therefore concentrated in the period when a generic applicant seeks approval with labeling that includes hemodialysis dosing. Key Takeaways
FAQsCan a generic ceftolozane-tazobactam product launch before June 2034?Yes. Launch could occur after a successful Paragraph IV challenge, a settlement providing an earlier entry date, a license from the patent holder, or an approved label that omits the patented method. Does US 10,376,496 cover all Zerbaxa patients with kidney impairment?No. The claims require end-stage renal disease and hemodialysis. They do not broadly cover every patient with renal impairment or every reduced-dose regimen. Does metronidazole automatically create infringement under claim 5?No. Claim 5 requires the complete claim 1 regimen, cIAI treatment and administration of a therapeutically effective amount of metronidazole. Metronidazole alone is not enough. Can a manufacturer avoid claims 7 and 8 by administering the dose before hemodialysis?Potentially, but the manufacturer would still need to assess claims 1 through 6 and any other Zerbaxa patents. Avoiding a dependent claim does not avoid infringement of the independent claim if all of its limitations are met. Are biosimilars relevant to Zerbaxa?No. Zerbaxa is a small-molecule antibacterial drug, so the primary competitive threat is from ANDA-based generic products, not biosimilars under the Public Health Service Act. References
More… ↓ |
Drugs Protected by US Patent 10,376,496
| 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 |
International Family Members for US Patent 10,376,496
| 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 | |||
| European Patent Office | 3043797 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
