Details for Patent: 8,071,643

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Which drugs does patent 8,071,643 protect, and when does it expire?

Patent 8,071,643 protects XENLETA and is included in two NDAs.

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

Summary for Patent: 8,071,643

Title:	Pleuromutilin derivatives for the treatment of diseases mediated by microbes
Abstract:	A pleuromutilin derivative compound of general formula (I)
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:	US12/531,839
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,071,643
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 8,071,643: Scope, Claims, Expiration, and Pleuromutilin Patent Landscape

US Patent 8,071,643 covers a broad genus of semisynthetic pleuromutilin antibiotics, including thiol-linked cyclohexyl derivatives attached at the 14-position of mutilin. Its strongest protection is the composition-of-matter coverage in claims 1-7. Claims 8-11 extend that protection to salts, drug substances, pharmaceutical compositions, and combinations with other active agents. The patent is associated with the pleuromutilin program that produced lefamulin, marketed in the United States as Xenleta, although the supplied claims cover substantially more compounds than lefamulin itself. [1,2]

The patent is materially narrower than a claim to all pleuromutilins but materially broader than a claim limited to one clinical candidate. It covers multiple stereochemical configurations, substituted amino-cyclohexyl groups, dihydromutilin analogs, salts, dosage-form ingredients, and combination products.

What does US Patent 8,071,643 protect?

The patent protects compounds based on a mutilin or dihydromutilin core bearing a 14-O-acetyl substituent linked through sulfur to a substituted cyclohexane ring. The central structural motif is:

• a pleuromutilin or 19,20-dihydropleuromutilin nucleus;
• a 14-O-acetyl linkage;
• a sulfur atom connecting the acetyl side chain to a substituted cyclohexyl group;
• an amino, substituted amino, hydroxy, alkoxy, halogen, or related substituent on the cyclohexyl ring;
• defined stereochemistry and positional relationships between sulfur and the R3 substituent.

The claims use both broad generic formulas and a long list of specifically named compounds.

Core claim architecture

Claim	Subject matter	Commercial significance
1	Broad genus of formula (I) compounds	Principal composition-of-matter claim
2	Formula (II) compounds	Separate structural subclass
3	Formula (III) compounds	Separate structural subclass
4	Formula (IV) compounds	Narrower ring or linker subclass
5	Formula (V) compounds	Narrower structural subclass
6	Formula (VI) compounds	Narrower structural subclass
7	Enumerated compounds within claim 1	Species-level fallback protection
8	Salts of claim 1 compounds	Protects pharmaceutical salt forms
9	Drug substances comprising claim 1 compounds	Substance-level pharmaceutical coverage
10	Pharmaceutical compositions with excipients	Formulation and product coverage
11	Compositions with another active agent	Combination-product coverage

Claims 2-6 depend on structural formulas that are not reproduced in the supplied text. Their precise ring topology and substituent boundaries therefore must be read from the issued patent drawings and specification. The claim language confirms that they inherit the n, R, R1, R2, and R3 definitions from claim 1, but the exact compounds covered by each subclass cannot be determined from the text alone. [1]

How broad is claim 1 of US 8,071,643?

Claim 1 is a Markush composition-of-matter claim. It is broad because it covers a variable set of substituents, ring positions, chain lengths, stereochemical forms, and nitrogen substituents.

Structural variables in claim 1

Variable	Permitted scope
n	0 through 4
m	0 or 1, subject to a vicinal-position proviso
R	Ethyl or vinyl
R1	Hydrogen or C1-C6 alkyl, subject to alternatives
R2	Hydrogen, C3-C6 cycloalkyl, unsubstituted C1-C6 alkyl, or substituted C1-C6 alkyl
R1/R2 together	Five- to seven-membered nitrogen heterocycle, optionally containing N or O
Special nitrogen arrangement	R1 hydroxy and R2 formyl
R3	Hydroxy, alkoxy, halogen, or cyclic acetal-type O-(CH2)p-O group
p	2 or 3
R4	Unsubstituted C1-C6 alkyl or C3-C6 cycloalkyl

The claim reaches primary, secondary, and tertiary amino substituents. It also covers amino substituents carrying hydroxyalkyl, methoxyalkyl, cycloalkyl, allyl, and morpholine-related functionality, provided the accused compound falls within the defined formula and stereochemical limitations.

Key limitations that restrict claim breadth

Claim 1 is not an unrestricted claim to every amino-substituted pleuromutilin. The following limitations are important:

1. The sulfur atom and R3 must occupy vicinal positions under the claim's m-dependent positional rules.
2. R is limited to ethyl or vinyl.
3. The amino substituent is constrained by the definitions of R1 and R2.
4. The cyclohexyl ring has defined substitution patterns and stereochemical relationships.
5. The claim requires the specified mutilin-linked sulfur-acetyl architecture.
6. The claim does not automatically cover unrelated pleuromutilin modifications at other positions.

A potentially competing molecule can avoid literal infringement by changing the core attachment point, removing the sulfur linkage, moving the amino substituent outside the permitted positions, using a prohibited substituent, or selecting a stereochemical arrangement outside the claim.

What compounds are listed in claim 7?

Claim 7 provides species-level coverage for numerous named compounds. The list includes:

• amino-cyclohexylsulfanyl mutilin derivatives;
• ethylamino and diethylamino analogs;
• methylamino, allylamino, and substituted amino derivatives;
• morpholine-containing derivatives;
• cyclopropylamino and cyclohexylamino compounds;
• aminoalkyl and methylaminoalkyl derivatives;
• formyl-hydroxy-amino compounds;
• 19,20-dihydromutilin analogs;
• chloro and methoxy cyclohexyl compounds;
• spirocyclic amino derivatives.

The claim also identifies multiple enantiomers and diastereomers. This is significant because stereochemistry is central to pleuromutilin antibacterial activity, pharmacokinetics, and infringement analysis.

Claim 7 drafting observations

The supplied claim text contains several apparent transcription or nomenclature inconsistencies, including:

• use of “R*” stereochemical notation;
• compounds described as diastereomers without complete stereochemical designation;
• an apparent positional inconsistency in the compound described as a 5-substituted cyclohexyl derivative carrying a “4-cyclopropylamino” group;
• inconsistent spacing and punctuation in several chemical names.

For enforcement, the issued patent, certified prosecution history, and chemical structures control over a transcription of the claim text. Chemical names alone should not be used to determine the final scope of a species claim where the patent includes structural drawings or corrected claim language.

Does US 8,071,643 cover lefamulin?

The patent belongs to the pleuromutilin derivative family underlying lefamulin, but the supplied claims should not be treated as a direct claim to every commercial form of lefamulin without a structure-to-claim mapping.

Lefamulin is a semisynthetic pleuromutilin antibacterial approved by the FDA for community-acquired bacterial pneumonia in adults. The FDA label identifies Xenleta as lefamulin acetate, administered intravenously or orally. [2]

The relevant legal question is whether the commercial active moiety, salt, or pharmaceutical product falls within one or more issued claims. That analysis requires:

• the exact molecular structure of lefamulin;
• the stereochemistry used in the approved product;
• whether the marketed material is the free base or a salt;
• the scope of the issued claims as construed;
• any later Orange Book-listed patents that separately protect the approved product or formulation.

Claim 8 is particularly relevant to an approved salt because it covers salts of compounds falling within claim 1. Claims 9 and 10 may also be relevant to the drug substance and pharmaceutical composition.

When does US Patent 8,071,643 lose exclusivity?

US Patent 8,071,643 issued on December 6, 2011. The patent originated from the pleuromutilin derivative patent family associated with Nabriva Therapeutics AG. Its ordinary US patent term is generally calculated from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any patent-term extension. [1,3]

Public patent-family records commonly associate the patent with an effective term reaching into approximately 2026. The exact enforceable expiration date must be determined from the USPTO patent-term data and the patent's face record. A patent's expiration date is separate from FDA regulatory exclusivity and from the expiration dates of later patents covering lefamulin formulations, methods of treatment, or manufacturing processes.

Exclusivity timeline

Event	Date or period
Pleuromutilin derivative priority and filing activity	Mid-2000s patent-family period
US 8,071,643 issued	December 6, 2011
FDA approval of Xenleta	August 19, 2019
Core patent term	Approximately mid-2020s, subject to USPTO term calculation
FDA new chemical entity exclusivity	Four years from approval, expiring in 2023
FDA five-year NCE approval exclusivity	Five years from approval, subject to applicable filing rules
Later product and formulation patent coverage	Extends beyond the core patent in the Xenleta portfolio

The four-year and five-year FDA exclusivity periods do not themselves prevent all later regulatory activity in the same way as a patent. Patent rights and FDA exclusivity operate independently. [2,4]

What is the Orange Book status of lefamulin and Xenleta?

The FDA Orange Book lists patents associated with approved drug products when the sponsor submits eligible patent information and FDA accepts the listing. Xenleta's listed patent estate includes patents directed to the active ingredient, pharmaceutical compositions, dosing, and related product features. [4]

US 8,071,643 should be analyzed as an early composition-of-matter patent in the lefamulin family rather than as the entire Orange Book estate. Later patents may have greater practical importance after expiration of the original compound patent.

Orange Book risk categories

Patent category	Typical protected subject matter	Generic challenge relevance
Composition of matter	Lefamulin or a covered pleuromutilin derivative	Highest
Salt or drug substance	Approved active form	High
Formulation	Oral or intravenous product composition	Moderate to high
Method of treatment	Treatment of bacterial pneumonia or related infections	Depends on labeling
Dosing regimen	Frequency, duration, or patient population	Relevant to label carve-outs
Manufacturing	Crystallization, purification, or process steps	Relevant to supply-chain design

The presence of a patent in the Orange Book does not establish validity or infringement. It identifies patents that may create a listed patent certification obligation for an abbreviated new drug application.

Which companies could challenge the lefamulin patent estate?

Potential challengers include generic manufacturers with an interest in oral and intravenous antibiotics, contract manufacturers developing a lefamulin active pharmaceutical ingredient, and companies seeking a Paragraph IV launch before expiration of later-listed patents.

No conclusion about a specific company's Paragraph IV filing, litigation position, or settlement can be drawn solely from the supplied claim text. A complete challenger assessment requires current FDA Orange Book records, ANDA litigation dockets, Paragraph IV notices, and district-court filings.

Paragraph IV issues

A generic applicant challenging a listed patent may certify under Paragraph IV that the patent is invalid, unenforceable, or will not be infringed. For a compound claim like claim 1, the likely technical issues include:

• anticipation by an earlier pleuromutilin reference;
• obviousness based on pleuromutilin chemistry and antibacterial structure-activity data;
• written-description support for the full Markush genus;
• enablement across the permitted substituent and stereochemical combinations;
• indefiniteness in positional or stereochemical limitations;
• infringement of the approved compound or salt;
• prosecution-history estoppel affecting claim interpretation.

The long list of specific compounds in claim 7 can strengthen written-description arguments for selected species, while the broad genus in claim 1 remains more exposed to enablement and obviousness challenges.

How strong is the patent estate for lefamulin?

The estate appears strongest where the accused product is the same stereochemically defined active compound or its covered salt. It is weaker against a genuinely different pleuromutilin analog that changes the sulfur-linked cyclohexyl architecture or falls outside the enumerated substituent classes.

Strength by claim type

Claim type	Relative strength	Reason
Specific species claims	High for listed compounds	Clear chemical identity and stereochemical definition
Broad genus claim	Moderate to high	Broad commercial reach, but greater validity exposure
Salt claims	Moderate	Depends on whether the salt is within the parent compound claim
Drug-substance claims	Moderate	Scope depends on construction of “drug substance” language
Composition claims	Moderate	May be avoided through formulation redesign
Combination claims	Variable	Requires presence of another active agent and all claim limitations

The commercial value of claim 1 depends on whether the approved lefamulin structure is inside the genus and whether later patents provide overlapping protection. If claim 1 covers the commercial active ingredient, it is the principal barrier to an early generic launch before its expiration.

What formulation patents protect lefamulin?

Claim 10 covers a pharmaceutical composition containing a claim 1 compound and at least one pharmaceutical excipient. This is a functional composition claim, not a detailed formulation claim limited to a particular excipient, concentration, dosage form, release profile, or manufacturing process.

A generic formulation may avoid claim 10 if its active ingredient is outside claim 1. If the active ingredient is inside claim 1, changing excipients may not avoid the claim because the claim requires only the covered compound in association with at least one pharmaceutical excipient.

Later formulation patents may be narrower and may cover:

• oral tablets;
• intravenous solutions;
• specific salt forms;
• pH ranges;
• stabilizers;
• solubilizers;
• container systems;
• dosing schedules;
• manufacturing or purification methods.

The scope of claim 10 should therefore be assessed separately from later, more technically specific formulation patents.

Does the patent create biosimilar risk?

No. Lefamulin is a small-molecule antibacterial, not a biologic. The relevant regulatory pathway is an ANDA for a generic drug, not a biosimilar application under the Public Health Service Act.

The primary regulatory risks are:

• Paragraph IV certification;
• 30-month litigation stay;
• bioequivalence for oral products;
• comparative pharmaceutical equivalence;
• intravenous formulation requirements;
• patent-term and Orange Book timing;
• potential labeling carve-outs for method-of-use patents.

What manufacturing and intellectual-property barriers remain?

Manufacturing barriers may remain even after expiration of the core composition patent. Pleuromutilin derivatives can present process challenges involving:

• stereochemical control;
• regioselective functionalization;
• sulfur-containing intermediates;
• purification of diastereomers;
• salt selection;
• solid-state form;
• impurity control;
• scale-up of semisynthetic transformations.

A process patent cannot extend the life of an expired composition patent against all manufacture, but it can create infringement risk if the generic uses a protected route or purification process. Process patents also affect API sourcing and may require a noninfringing supplier.

How does US 8,071,643 compare with later lefamulin patents?

US 8,071,643 is primarily a foundational compound patent. Later patents in the lefamulin portfolio may be more narrowly directed to the approved product, formulations, dosing regimens, crystalline forms, or manufacturing methods.

Patent layer	Main function	Likely expiration profile
US 8,071,643	Broad pleuromutilin compound genus and listed species	Earliest major patent barrier
Later composition patents	Specific commercial compound or salt	Potentially later
Formulation patents	Oral or IV dosage forms	Potentially later
Method patents	Pneumonia treatment and dosing	Label-dependent
Process patents	API preparation and purification	Supplier and route-dependent

A generic launch after expiration of US 8,071,643 may still face later patents. The commercial launch analysis must use the latest unexpired Orange Book-listed patent, not the earliest composition patent alone.

What litigation and settlement issues affect the patent?

The principal litigation risks concern Paragraph IV challenges to Orange Book-listed patents. Relevant issues include:

• whether an ANDA applicant sent a valid Paragraph IV notice;
• whether the sponsor sued within the statutory 45-day period;
• whether a 30-month stay applies;
• whether the parties entered a settlement;
• whether the settlement includes a licensed entry date;
• whether the settlement contains authorized-generic terms;
• whether a later patent is listed after the ANDA filing.

No settlement date or agreed generic-entry date is established by the supplied material. Those facts must be verified against FDA records and federal court dockets before being used in a launch forecast.

What is the likely generic launch scenario?

The commercial scenarios are:

1. No challenge before core-patent expiry. Entry occurs after expiration of the composition patent, subject to later Orange Book patents.
2. Paragraph IV challenge. Entry may occur after a successful validity or noninfringement judgment, a settlement date, or expiration of the 30-month stay.
3. Section viii carve-out. A generic may omit patented methods from its label if the remaining indication and labeling support approval.
4. Authorized generic. The innovator or licensee may introduce an authorized generic before independent ANDA entry.
5. Later-patent delay. A generic may clear the original composition patent but remain blocked by formulation, salt, dosing, or process patents.

Revenue exposure is therefore concentrated in the transition from protected branded sales to generic oral and intravenous competition. The commercial impact depends on the number of approved generic suppliers, hospital formulary adoption, intravenous manufacturing capacity, and whether later patents delay substitution.

Key Takeaways

• US 8,071,643 is a pleuromutilin composition-of-matter patent with broad Markush coverage.
• Claim 1 reaches multiple amino-substituted, hydroxy-substituted, alkoxy-substituted, halogenated, and cyclic derivatives.
• Claim 7 supplies species-level protection for numerous stereochemically defined compounds.
• Claims 8-11 extend coverage to salts, drug substances, pharmaceutical compositions, and combinations.
• The patent is associated with the lefamulin/Xenleta development program but does not replace analysis of later lefamulin patents.
• Lefamulin is a small molecule, so biosimilar rules do not apply.
• Generic risk is governed by ANDA, Orange Book, Paragraph IV, formulation, dosing, salt, and process patents.
• The core patent's ordinary term reaches approximately into 2026, subject to the official USPTO term calculation.
• A freedom-to-operate opinion requires comparison of the marketed lefamulin structure and each later patent claim, not reliance on US 8,071,643 alone.

FAQs

Is US 8,071,643 a patent on lefamulin itself?

It is a foundational pleuromutilin derivative patent associated with the lefamulin program. Whether a particular commercial lefamulin form is literally covered must be confirmed by mapping its exact structure and salt to the issued claims.

Can a generic avoid claim 10 by changing excipients?

Changing excipients may not avoid claim 10 if the generic still contains a compound covered by claim 1 and at least one pharmaceutical excipient. A different active ingredient or a noninfringing compound structure would be more significant.

Does claim 7 protect every stereoisomer listed in the specification?

Claim 7 protects the named species to the extent the issued claim language and corresponding structures encompass them. Stereochemical symbols, corrections, and structural drawings must be read from the issued patent rather than from a transcription.

Can a generic launch after US 8,071,643 expires?

Not necessarily. Later patents covering lefamulin salts, formulations, dosing, methods of treatment, crystalline forms, or manufacturing processes may remain enforceable after the foundational patent expires.

Is a Paragraph IV challenge required for every lefamulin patent?

No. An ANDA applicant may use a Paragraph IV certification for a patent it challenges, a Paragraph III certification for a patent it accepts and awaits expiration of, or a Section viii statement for certain method-of-use patents it omits from labeling.

References

1. United States Patent and Trademark Office. (2011). US Patent No. 8,071,643, Pleuromutilin derivatives.
2. U.S. Food and Drug Administration. (2019). Xenleta (lefamulin acetate) prescribing information.
3. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.

Drugs Protected by US Patent 8,071,643

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	8,071,643		Y	Y
Hong Kong	XENLETA	lefamulin acetate	TABLET;ORAL	211672-001	Aug 19, 2019		RX	Yes	Yes	8,071,643		Y	Y

Foreign Priority and PCT Information for Patent: 8,071,643

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

PCT Information
PCT Filed	March 19, 2008	PCT Application Number:	PCT/AT2008/000097
PCT Publication Date:	September 25, 2008	PCT Publication Number:	WO2008/113089

International Family Members for US Patent 8,071,643

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
European Patent Office	2137143		301086	Netherlands
European Patent Office	2137143		132020000000167	Italy
European Patent Office	2137143		122020000080	Germany