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Details for Patent: 10,376,499
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Which drugs does patent 10,376,499 protect, and when does it expire?
Patent 10,376,499 protects XACDURO (COPACKAGED) and is included in one NDA.
This patent has thirty-five patent family members in thirty-one countries.
Summary for Patent: 10,376,499
| Title: | Combination therapy for treatment of resistant bacterial infections | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The present invention is directed to combinations of a β-lactamase inhibitor with sulbactam and, optionally, imipenem/cilastatin. The combinations are useful for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant pathogens. More particularly, the invention relates to a combination of β-lactamase inhibitor compound 1: or a pharmaceutically acceptable salt thereof, with sulbactam, or a pharmaceutically acceptable salt thereof, and, optionally, imipenem/cilastatin, or a pharmaceutically acceptable salt thereof. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Boudewijn Lodewijk Maria DeJonge, Thomas Francois Durand-Reville, Jeroen Cunera Verheijen, Ruben Tommasi, John Mueller | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Entasis Therapeutics Ltd | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US15/947,959 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 10,376,499: Durlobactam-Sulbactam Claims, Orange Book Status, Exclusivity and Generic Entry RiskUS Patent No. 10,376,499 protects combinations of durlobactam, also known as ETX2514, with sulbactam, including the sodium-salt form, pharmaceutical compositions, and treatment of infections caused by Enterobacteriaceae, Acinetobacter species, Pseudomonas aeruginosa, and Burkholderia species. The patent is central to the intellectual-property position for Xacduro, the intravenous sulbactam-durlobactam product approved by the FDA for hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible Acinetobacter baumannii-calcoaceticus complex. The patent is composition- and method-of-use focused. It does not claim every use of sulbactam or every beta-lactamase inhibitor. Its commercial relevance depends on whether a competing product contains durlobactam, uses the claimed combination, or practices one of the claimed treatment methods. What does US Patent 10,376,499 cover?The patent covers a combination consisting essentially of durlobactam, or a pharmaceutically acceptable salt, and sulbactam, or a pharmaceutically acceptable salt. The claims can be grouped into four categories:
Claim 1 is the principal composition claim. Claim 5 is the principal method-of-treatment claim. Claims 8 and 9 narrow the method claims by specifying bacterial pathogens. What is the claimed beta-lactamase inhibitor?The beta-lactamase inhibitor identified in the issued patent is durlobactam, also called ETX2514. Durlobactam is a diazabicyclooctane beta-lactamase inhibitor developed to inhibit class A, class C, and some class D beta-lactamases, including enzymes associated with multidrug-resistant Acinetobacter. Durlobactam is administered clinically as durlobactam sodium. Xacduro combines durlobactam sodium with sulbactam sodium. The identity of durlobactam is essential to claim construction. The phrase "the beta-lactamase inhibitor" is not an unrestricted claim to any beta-lactamase inhibitor. It refers to the inhibitor defined in the patent specification and claims, including the relevant chemical structure, stereochemistry, salts, and pharmaceutical forms. How broad are the composition claims?Claim 1 is broad within the durlobactam-sulbactam combination field. It does not require ampicillin, cefoperazone, a particular dosage, a particular ratio, a particular formulation, or a particular bacterial species. That breadth creates several potential infringement paths:
The phrase "consisting essentially of" is narrower than "comprising" but broader than "consisting of." It generally permits additional components that do not materially affect the basic and novel characteristics of the claimed combination. In this patent, the basic combination is durlobactam plus sulbactam. Excipients and other formulation components are expressly addressed in dependent claim 2. A competing product containing a materially different active beta-lactamase inhibitor would not ordinarily fall within claim 1 merely because it is combined with sulbactam. What formulations are protected by US 10,376,499?Claim 2 extends the combination to pharmaceutical compositions containing:
Claim 3 specifically covers durlobactam in sodium-salt form. Claim 4 adds ampicillin or cefoperazone to the combination of claim 1. The formulation claims are important because they reach more than the active-ingredient pairing. A generic or follow-on manufacturer could avoid a formulation claim by changing inactive ingredients, but that would not necessarily avoid claim 1 if the product still contains durlobactam and sulbactam. The patent does not, based on the listed claims, require:
Those limitations may appear in the specification or other patents in the family, but they are not apparent from the claims supplied. What method-of-use patents does US 10,376,499 contain?Claims 5 through 9 cover treatment methods. The core method requires administering effective amounts of durlobactam and sulbactam to a patient with a bacterial infection. The pathogen claims cover:
The method claims are not limited to hospital-acquired pneumonia or ventilator-associated pneumonia. They are directed to bacterial infection generally, subject to the pathogen limitations in claims 8 and 9. This creates a distinction between patent scope and FDA labeling. The patent claims reach certain infections beyond the approved Xacduro indication, while the FDA-approved label is narrower. How does the patent relate to Xacduro's FDA indication?The FDA approved Xacduro on May 23, 2023, for adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible Acinetobacter baumannii-calcoaceticus complex [1]. The labeled regimen uses intravenous sulbactam and durlobactam, generally administered every six hours by infusion, with renal-dose adjustments. Xacduro's approved indication aligns most directly with the Acinetobacter method claims, particularly claim 9. The patent does not automatically confer FDA approval for every infection identified in claims 5 through 9. Patent rights and regulatory approval operate separately. When does US Patent 10,376,499 expire?US Patent 10,376,499 was granted on August 13, 2019, and is commonly reported with an expiration date in May 2035. The relevant patent term is based primarily on the earliest effective nonprovisional or international filing date, subject to patent-term adjustment and any applicable regulatory patent-term extension.
The exact terminal date should be determined from the USPTO patent-term calculation and the current FDA Orange Book listing. Patent expiry can differ from a simple 20-year calculation because of patent-term adjustment, terminal disclaimers, patent-term extension, or other prosecution events. Does Xacduro have FDA exclusivity separate from the patent?Yes. Xacduro received new chemical entity exclusivity for durlobactam, generally providing five years of regulatory exclusivity from FDA approval. That period is separate from patent protection. NCE exclusivity generally prevents submission of an ANDA or 505(b)(2) application relying on the product's approval during the protected period, subject to the statutory rules for Paragraph IV patent certifications. It does not prevent all clinical development or all competing products under every FDA pathway. Patent protection extends beyond the NCE period and is therefore the principal barrier to ordinary generic entry after regulatory exclusivity ends. What is the Orange Book status of US 10,376,499?US Patent 10,376,499 has been associated with Xacduro's listed patent estate. The Orange Book is the operative source for current listing status, patent-use codes, and any reported expiration or exclusivity information [2]. The patent's practical Orange Book relevance is strongest for:
A method patent listed in the Orange Book can require an ANDA applicant to certify under Paragraph IV if the applicant seeks approval for a use covered by the listed patent. An applicant may also use a section viii statement to carve out a patented method of use, provided the proposed labeling avoids the protected indication. How does Paragraph IV risk apply to this patent?A generic applicant seeking approval for a product containing durlobactam and sulbactam would likely confront the patent through one or more of the following positions:
A Paragraph IV certification could challenge the patent on:
The strongest practical barrier is claim 1. A section viii carve-out may avoid claims directed only to an approved treatment method, but it would not remove a composition claim covering the active combination. No publicly established Paragraph IV judgment or settlement concerning US 10,376,499 is identified in the materials supplied. The absence of a known judgment does not establish that no certification, notice letter, or confidential settlement exists. Which companies own or commercialize the relevant rights?Entasis Therapeutics developed durlobactam and its combination with sulbactam. Innoviva acquired Entasis in 2022 and has commercialized Xacduro through Innoviva Specialty Therapeutics [3]. Zai Lab has been associated with development and commercialization rights for sulbactam-durlobactam in Greater China under a collaboration arrangement with Entasis. Territorial licensing does not eliminate the US patent owner's rights; it allocates commercial rights and enforcement responsibilities by jurisdiction. The principal US commercial parties are therefore:
How strong is the patent estate for durlobactam-sulbactam?US 10,376,499 is commercially strong because claim 1 directly covers the two active ingredients in Xacduro. A competitor using the same active combination would have difficulty avoiding the core composition claim through changes to packaging, excipients, infusion time, or vial configuration. Its main limitations are:
The estate is stronger against a direct durlobactam-sulbactam generic than against competitive products such as cefiderocol or meropenem-vaborbactam. What manufacturing and formulation barriers exist?Durlobactam-sulbactam is an intravenous sterile product. A generic manufacturer must reproduce or independently establish:
Those requirements are separate from patent infringement. They can delay entry even where a patent challenge succeeds. How does durlobactam-sulbactam compare with competing beta-lactamase inhibitor products?
These products do not ordinarily infringe claim 1 because they use different beta-lactamase inhibitors and, in most cases, different beta-lactam antibiotics. They remain commercial substitutes and may reduce the revenue available to Xacduro without creating direct patent-infringement exposure. What generic entry scenarios exist for Xacduro?The principal scenarios are:
Because US 10,376,499 directly covers the active combination, a successful generic launch before patent expiry would most likely require invalidation, a non-infringement position based on product composition, or a settlement granting an agreed entry date. Key Takeaways
FAQs About US Patent 10,376,499Is US Patent 10,376,499 a patent on sulbactam alone?No. The patent claims sulbactam in combination with durlobactam. It does not broadly claim sulbactam as an isolated antibiotic or beta-lactamase inhibitor. Does the patent cover durlobactam used without sulbactam?The supplied claims require both durlobactam and sulbactam. They do not, on their face, cover durlobactam administered alone. Can a generic manufacturer avoid the patent by using a different durlobactam salt?Not necessarily. The claims expressly include pharmaceutically acceptable salts, and claim 3 specifically addresses the sodium salt. A different salt would require a separate infringement and claim-construction analysis. Does US 10,376,499 block treatment of infections outside the FDA-approved Xacduro indication?The patent's method claims identify several pathogen groups beyond the narrow FDA indication. Patent coverage can therefore be broader than the approved label. Is there biosimilar competition to Xacduro?No conventional biosimilar pathway applies because Xacduro is a small-molecule drug. Competition would generally proceed through an ANDA, a 505(b)(2) application, or an alternative antimicrobial product. References
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Drugs Protected by US Patent 10,376,499
| 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 | 10,376,499 | ⤷ Start Trial | Y | TREATMENT OF HOSPITAL-ACQUIRED BACTERIAL PNEUMONIA AND VENTILATOR-ASSOCIATED BACTERIAL PNEUMONIA (HABP/VABP) | ⤷ 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 10,376,499
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Australia | 2015350128 | ⤷ Start Trial | |||
| Brazil | 112017010132 | ⤷ Start Trial | |||
| Canada | 2966632 | ⤷ Start Trial | |||
| China | 107108624 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
