Details for Patent: 8,153,689

Which drugs does patent 8,153,689 protect, and when does it expire?

Patent 8,153,689 protects XENLETA and is included in two NDAs.

This patent has forty-five patent family members in thirty-one countries.

Summary for Patent: 8,153,689

Title:	Pleuromutilin derivatives for the treatment of diseases mediated by microbes
Abstract:	Disclosed are pleuromutilin derivatives of formula (I) and their use in the treatment of diseases mediated by microbes.
Inventor(s):	Rosemarie Mang, Werner Heilmayer, Rudolf Badegruber, Dirk B. Strickmann, Rodger Novak, Mathias Ferencic, Atchyuta Rama Chandra Murty Bulusu
Assignee:	Hong Kong King Friend Industrial Co Ltd , Kreos Capital IV UK Ltd
Application Number:	US13/252,732
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 8,153,689: Lefamulin Claim Scope, Exclusivity, Orange Book Status, and Patent Landscape

US Patent No. 8,153,689 protects compositions containing lefamulin, a semisynthetic pleuromutilin antibiotic, including specified pharmaceutically acceptable salts and excipient-containing formulations. The patent does not expressly claim a method of treating pneumonia, a dosage regimen, intravenous administration, oral tablets, or a manufacturing process. Its principal commercial value is the composition claim covering the lefamulin active pharmaceutical ingredient, subject to claim construction, patent validity, and regulatory exclusivity.

The patent issued April 10, 2012, from an application claiming an April 10, 2006 priority date. The reported patent term runs to April 10, 2027, subject to any applicable patent-term adjustment or extension reflected in official USPTO records. Lefamulin was approved by the FDA as Xenleta in 2019 for community-acquired bacterial pneumonia in adults. FDA regulatory exclusivity and patent exclusivity are separate rights and should be analyzed independently. [1]-[4]

What drug does US Patent 8,153,689 protect?

US 8,153,689 protects lefamulin compositions. The claimed compound is:

14-O-{[(1R,2R,4R)-4-amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

The compound is also known as lefamulin and was previously associated with development code BC-3781. Lefamulin belongs to the pleuromutilin class and inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit.

Patent identification

Field	Details
U.S. patent	8,153,689
Patent type	Utility patent
Issue date	April 10, 2012
Earliest priority date	April 10, 2006
Applicant/assignee history	Associated with Nabriva Therapeutics and predecessor entities
Protected product	Lefamulin compositions
Commercial product	Xenleta
Dosage forms marketed	Oral tablets and intravenous injection
Reported expiration	April 10, 2027
Therapeutic class	Pleuromutilin antibacterial
FDA approval	August 19, 2019

The patent should be reviewed together with its assignment history, terminal-disclaimer records, patent-term-adjustment calculation, and Orange Book listing. Patent expiration dates shown in commercial databases can differ if later USPTO term information changes.

What do the claims of US 8,153,689 cover?

The five claims form a compact composition-claim set centered on lefamulin.

Claim 1: composition containing lefamulin

Claim 1 covers:

A composition comprising the claimed lefamulin compound.

The term “comprising” generally makes the claim open-ended. A composition may contain lefamulin together with other active ingredients, carriers, solvents, stabilizers, buffers, preservatives, or excipients, provided the composition includes the claimed compound.

The claim does not require:

• A particular amount of lefamulin
• A particular concentration
• A specific dosage form
• Oral or intravenous administration
• A particular disease indication
• A particular excipient
• A specific manufacturing method
• A particular crystalline, amorphous, or polymorphic form, unless such a limitation is imported from the specification or construed by a court

Claim 1 is therefore broad as a product-composition claim. It is narrower than a claim to the compound itself in every possible context because it requires a composition, but it can reach a wide range of pharmaceutical and non-pharmaceutical compositions containing lefamulin.

Claim 2: pharmaceutically acceptable salts

Claim 2 depends on claim 1 and requires the claimed compound to be present as a pharmaceutically acceptable salt.

This claim does not cover every conceivable salt unless the salt qualifies as pharmaceutically acceptable. The limitation is functional and technical. It focuses on salts suitable for pharmaceutical use, including salts that improve handling, solubility, stability, crystallinity, or formulation performance.

Claim 3: enumerated salt species

Claim 3 narrows claim 2 to a specified list of salts. The list includes:

• Sodium
• Potassium
• Calcium
• Magnesium
• Trimethylammonium
• Isopropylamine
• Diethylamine
• Ethanolamine
• Trimethylamine
• Dicyclohexylamine
• N-methyl-D-glucamine
• Hydrogen fumarate and fumarate
• Tartrate
• Ethane-1,2-disulfonate
• Naphthalene-1,5-disulfonate
• Acetate
• Maleate
• Succinate
• Salicylate
• Azelate
• Diclofenac-type salt identified by the claim as 2-[(2,6-dichlorophenyl)amino]benzene acetic acid
• Hydrochloride

Claim 3 is materially narrower than claim 2. A product containing a lefamulin salt outside the listed group could fall within claim 2 while avoiding literal infringement of claim 3, subject to the scope of claim 2 and the doctrine of equivalents.

Claims 4 and 5: excipient-containing compositions

Claim 4 covers the free compound with at least one pharmaceutically acceptable excipient.

Claim 5 covers a pharmaceutically acceptable salt with at least one pharmaceutically acceptable excipient.

These claims are directed to pharmaceutical formulations rather than the active ingredient alone. They may be relevant to tablets, capsules, injectable solutions, suspensions, or other dosage forms, depending on the formulation disclosure and claim construction.

How broad is the “composition comprising” language?

The principal breadth of claim 1 comes from the combination of a defined chemical entity and open-ended composition language.

A potentially infringing composition could include lefamulin with:

• One or more excipients
• A second antibiotic
• A buffer system
• An injectable vehicle
• A tablet matrix
• A coating
• A stabilizer
• A preservative
• A solvent or co-solvent

The claim does not appear limited to a commercial Xenleta formulation. A generic manufacturer would therefore need to assess whether its product contains the claimed lefamulin molecule, whether the product uses a salt form, and whether any formulation or labeling claim creates exposure under related patents.

The claim may not reach:

• A composition containing only a different pleuromutilin
• A composition containing a stereoisomer that is outside the claimed configuration
• A prodrug that does not contain the claimed compound in the claimed form
• A process for making lefamulin, without a claimed composition
• A method of administering lefamulin, absent a method-of-use claim in another patent

What formulations are protected by US 8,153,689?

The patent claims excipient-containing compositions but does not, based on the supplied claims, identify a particular tablet or injectable formulation.

Product characteristic	Claim relevance
Lefamulin free compound	Potentially claim 1
Lefamulin pharmaceutically acceptable salt	Potentially claim 2
Listed salt in claim 3	Potentially claim 3
Free compound plus excipient	Potentially claim 4
Salt plus excipient	Potentially claim 5
Specific tablet composition	Not expressly required by supplied claims
Specific IV vehicle	Not expressly required by supplied claims
Specific dose or schedule	Not expressly required by supplied claims
Specific polymorph	Not expressly required by supplied claims

Claims 4 and 5 could cover a broad range of pharmaceutical products because “at least one pharmaceutically acceptable excipient” is a low-threshold limitation. A formulation containing lefamulin and a conventional excipient may satisfy the structural limitations if the other claim elements are met.

A complete freedom-to-operate assessment still requires comparison against later patents directed to particular salt forms, polymorphs, particle sizes, dosage forms, injectable formulations, release profiles, or manufacturing controls.

When does US 8,153,689 lose patent exclusivity?

The reported expiration date is April 10, 2027.

Exclusivity category	Date or period	Significance
Earliest priority	April 10, 2006	Establishes the disclosed priority chain
Patent issue	April 10, 2012	Patent became enforceable, subject to applicable rules
FDA approval of Xenleta	August 19, 2019	Began product commercialization
Reported patent expiration	April 10, 2027	End of ordinary patent term
QIDP-related regulatory protection	Extends FDA exclusivity beyond ordinary NCE timing	Separate from patent term
Pediatric extension	Depends on FDA grant and applicable product exclusivity	Can add six months to qualifying exclusivity

The patent term should not be confused with FDA exclusivity. FDA exclusivity can restrict approval of competing applications even after a patent expires, while patent rights can continue after FDA exclusivity ends.

What is the Orange Book status of lefamulin?

Xenleta is an FDA-approved prescription drug marketed by Nabriva Therapeutics and associated commercial partners. FDA Orange Book records identify patent information submitted for approved drug products. The Orange Book listing must be checked by product, dosage form, strength, and current supplement because listed patents and expiration dates can change.

US 8,153,689 is associated with the core lefamulin composition and has been reported as an Orange Book-listed patent for Xenleta. The listing does not itself establish that every claim is valid or infringed. It indicates that the patent holder submitted patent information under the Hatch-Waxman framework. [2]

Regulatory exclusivity

Lefamulin received FDA approval for adults with community-acquired bacterial pneumonia. The product also received Qualified Infectious Disease Product status, which can provide an additional five years of exclusivity under the Generating Antibiotic Incentives Now provisions when statutory conditions are satisfied. [3]

The practical result is that a generic applicant may face both:

1. FDA approval restrictions based on unexpired regulatory exclusivity; and
2. Patent certification and litigation risks based on listed patents.

Are there Paragraph IV challenges to lefamulin patents?

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The filing of a Paragraph IV certification can trigger patent litigation and, in qualifying circumstances, a 30-month stay of FDA approval.

For lefamulin, a complete current assessment requires review of:

• FDA Orange Book patent listings
• FDA Paragraph IV certification notices
• ANDA litigation records
• District court dockets
• Patent Trial and Appeal Board proceedings
• Any authorized-generic or settlement announcements

The supplied patent claims create a straightforward infringement theory if a proposed generic contains lefamulin in a claimed composition. A generic applicant challenging US 8,153,689 would likely focus on claim construction, written description, enablement, anticipation, obviousness, and the scope of “pharmaceutically acceptable salt” and “composition comprising.”

No method-of-use limitation appears in the five supplied claims. A Paragraph IV defense would therefore be directed primarily to the composition itself rather than to the labeled indication.

What patent litigation affects lefamulin?

The core litigation risk for a generic manufacturer would arise from a listed patent suit filed after receipt of a Paragraph IV notice. Potential disputes include:

Issue	Relevance
Claim construction	Determines whether the generic composition contains the claimed compound
Chemical identity	Tests stereochemistry, salt state, and molecular structure
Anticipation	Assesses whether an earlier reference disclosed the claimed lefamulin composition
Obviousness	Tests whether the compound or composition would have been predictable
Written description	Examines support for the specific compound and salt list
Enablement	Examines whether the patent enables the full claimed composition scope
Infringement	Compares the generic product and formulation to the issued claims
Orange Book listing	Determines whether the patent can support a Hatch-Waxman action

The supplied claims are composition claims. They do not create a direct claim to a treatment method or to a manufacturing step. Separate patents could create additional litigation exposure even if US 8,153,689 were invalidated.

How does the patent estate compare with competing antibiotics?

Lefamulin competes in community-acquired bacterial pneumonia against macrolides, fluoroquinolones, tetracyclines, beta-lactams, and other newer antibacterial products.

Product	Active ingredient	Patent risk profile
Xenleta	Lefamulin	Core composition patent, formulation and regulatory exclusivity considerations
Nuzyra	Omadacycline	Multiple composition, formulation, and method-of-use patents
Fetroja	Cefiderocol	Composition, formulation, and antibacterial-use protections
Sivextro	Tedizolid	Product and formulation patent estate, with mature generic-entry analysis
Vibativ	Telavancin	Older product with a more advanced loss-of-exclusivity profile
Solithromycin candidates	Macrolide derivatives	Development-specific composition and use patents

Lefamulin’s principal distinction is that the supplied patent protects the active compound in composition form. A competitor does not avoid the patent merely by using a different dosage strength or a different excipient if the product still contains the claimed lefamulin compound.

How strong is the patent estate for lefamulin?

US 8,153,689 has meaningful claim breadth because claim 1 covers a composition containing the specifically defined lefamulin compound, while claims 2 through 5 address salts and excipient-containing pharmaceutical products.

Its main strengths are:

• Direct coverage of the commercial active ingredient
• Open-ended “comprising” language
• Coverage of both free compound and salt compositions
• Explicit salt enumeration
• Formulation coverage through excipient limitations
• Long remaining term relative to the 2019 approval date

Its principal limitations are:

• The claims do not expressly cover treatment methods
• The claims do not expressly cover a manufacturing process
• Claim 3 is limited to listed salts
• Claim 4 requires the free compound and an excipient
• Claim 5 requires a salt and an excipient
• Validity depends on the prior-art and disclosure record
• Claim scope may be affected by prosecution history and specification definitions

The patent is strongest against a generic product that uses the same lefamulin active ingredient in a conventional pharmaceutical composition. It is less comprehensive as a standalone estate because it does not, from the supplied claims, separately protect every formulation, polymorph, method of use, dosage regimen, or manufacturing intermediate.

What generic launch risks exist for lefamulin?

A generic launch before April 2027 would face several potential barriers:

1. Composition infringement. A product containing lefamulin may directly implicate claim 1.
2. Salt-form infringement. A pharmaceutical salt may implicate claim 2, and listed salts may implicate claim 3.
3. Formulation infringement. Excipients can bring a product within claims 4 or 5.
4. Regulatory exclusivity. QIDP or other exclusivity may delay FDA approval independently of patent status.
5. Litigation timing. A Paragraph IV notice could lead to a district court action and approval stay.
6. Additional patents. Later patents may cover dosage forms, salts, crystalline forms, formulations, or uses.
7. Commercial execution. Lefamulin requires differentiated oral and intravenous product strategies, with hospital and outpatient channels carrying different market-entry dynamics.

A “skinny label” strategy would have limited value against claims 1 through 5 because those claims are composition-based rather than indication-based. Removing a patented indication from the label does not avoid infringement of a product-composition claim if the drug product itself falls within the claim.

Are there licensing deals involving lefamulin?

Nabriva developed lefamulin and commercialized Xenleta through its U.S. operations and commercial arrangements. Public company disclosures describe financing, commercialization, and strategic arrangements involving Nabriva and its affiliates. Licensing and distribution rights should be separated from patent ownership because a commercial partner may have rights to market the product without owning the underlying patent.

For diligence, the relevant documents are:

• USPTO assignment records
• SEC filings by Nabriva and successor entities
• FDA product records
• Commercialization and distribution agreements
• Any settlement agreement resolving ANDA litigation
• Patent-license notices or security interests

Patent ownership, exclusive license rights, and marketing rights can reside with different entities.

What manufacturing and geographic barriers apply?

US 8,153,689 is a U.S. patent. It does not, by itself, establish protection in Europe, China, Japan, or other jurisdictions. International protection must be traced through the priority family and national-phase filings.

Manufacturing risk can arise even when a generic manufacturer avoids a particular formulation claim. Separate patent families may cover:

• Lefamulin intermediates
• Stereoselective synthesis
• Sulfanyl-acetyl coupling
• Salt preparation
• Crystallization
• Polymorph control
• Pharmaceutical-grade purification
• Injectable formulation
• Tablet manufacture

A U.S. generic applicant also faces the Hatch-Waxman safe harbor under 35 U.S.C. § 271(e)(1) for activities reasonably related to regulatory submission. Commercial manufacture, importation, sale, and offer for sale before patent expiry remain separate infringement issues. [5]

Key Takeaways

• US 8,153,689 is a core composition patent for lefamulin.
• Claim 1 broadly covers compositions comprising the specified lefamulin molecule.
• Claim 2 covers pharmaceutically acceptable salts.
• Claim 3 limits the salt protection to an enumerated list.
• Claims 4 and 5 cover excipient-containing pharmaceutical compositions.
• The supplied claims do not expressly cover treatment methods, dosage regimens, polymorphs, or manufacturing processes.
• The reported patent expiration date is April 10, 2027.
• FDA regulatory exclusivity, including potential QIDP protection, is separate from the patent term.
• A generic using lefamulin is exposed to composition-claim risk even if it changes the excipients or removes a treatment indication from its label.
• A full launch analysis must include later lefamulin patents, current Orange Book listings, assignment records, and any Paragraph IV litigation or settlement.

FAQs About US Patent 8,153,689 and Lefamulin

Does US 8,153,689 cover Xenleta tablets?

Potentially, if the tablets contain the claimed lefamulin compound and satisfy the applicable composition limitations. The claims supplied do not require a specific tablet formula.

Does the patent cover intravenous lefamulin?

Potentially. An injectable composition containing lefamulin may fall within claim 1, claim 2, claim 4, or claim 5 depending on the active form and excipients.

Can a generic avoid claim 3 by using a different lefamulin salt?

A different salt may avoid literal infringement of the enumerated salt claim in claim 3, but it could still fall within claim 2 if it is pharmaceutically acceptable. Other patents may also cover the alternative salt or its formulation.

Does a change in excipients avoid US 8,153,689?

Not necessarily. Claims 1 and 2 do not require a particular excipient. Claims 4 and 5 require at least one pharmaceutically acceptable excipient, which can encompass many conventional formulation ingredients.

Is a lefamulin biosimilar pathway available?

No. Lefamulin is a chemically synthesized small-molecule drug, not a biologic. A competing product would generally use the ANDA pathway, a 505(b)(2) application, or another applicable small-molecule route rather than the biosimilar pathway.

References

1. United States Patent and Trademark Office. (2012). U.S. Patent No. 8,153,689, compositions comprising 14-O-{[(1R,2R,4R)-4-amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. Center for Drug Evaluation and Research.

3. U.S. Food and Drug Administration. (2019, August 19). FDA approves new antibiotic for community-acquired bacterial pneumonia. Center for Drug Evaluation and Research.

4. U.S. Food and Drug Administration. (2019). Xenleta (lefamulin) prescribing information. Nabriva Therapeutics.

5. 35 U.S.C. § 271(e)(1). (2024). Infringement of patents relating to regulatory submissions. United States Code.

Drugs Protected by US Patent 8,153,689

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Hong Kong	XENLETA	lefamulin acetate	SOLUTION;INTRAVENOUS	211673-001	Aug 19, 2019		RX	Yes	Yes			Y	Y
Hong Kong	XENLETA	lefamulin acetate	TABLET;ORAL	211672-001	Aug 19, 2019		RX	Yes	Yes			Y	Y

Foreign Priority and PCT Information for Patent: 8,153,689

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	07450053	Mar 20, 2007

International Family Members for US Patent 8,153,689

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2137143		CA 2020 00046	Denmark
European Patent Office	2137143		PA2020531	Lithuania
European Patent Office	2137143		LUC00178	Luxembourg
European Patent Office	2137143		CR 2020 00046	Denmark