Details for Patent: 7,687,488

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Which drugs does patent 7,687,488 protect, and when does it expire?

Patent 7,687,488 protects EXBLIFEP and is included in one NDA.

This patent has eight patent family members in eight countries.

Summary for Patent: 7,687,488

Title:	2-substituted methyl penam derivatives
Abstract:	Novel 2-substituted methyl penam derivatives include the formula (I), their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their solvates, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them; wherein A=C or N; Het is a three- to seven-membered heterocyclic ring; R1 represents carboxylate anion, or —COOR4 where R4 represents hydrogen, carboxylic acid protecting group or a pharmaceutically acceptable salt; R2 and R3 may be same or different and independently represent hydrogen, halogen, amino, alkyl, protected amino, optionally substituted alkyl, alkenyl, alkynyl and the like; R represents substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, cycloalkyl, heterocyclyl or heterocyclylalkyl.
Inventor(s):	Senthilkumar Udayampalayam Palanisamy, Andrew Gnanaprakasam, Panchapakesan Ganapathy, Mukut Gohain, Venkatasubramanian Hariharan, Sriram Rajagopal, Maneesh Paul-Satyaseela, Shakti SINGH SOLANKI, Sathishkumar Devarajan
Assignee:	Allecra Therapeutics GmbH
Application Number:	US11/822,956
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 7,687,488: Scope, Claim Analysis, Expiration, and Penam Beta-Lactamase Inhibitor Landscape

US Patent 7,687,488 covers a broad genus of 2-substituted methyl penam compounds, including triazolium-substituted penam sulfones, their stereoisomers, salts, pharmaceutical compositions, combination products with beta-lactam antibiotics, and an alkylation process for making them. The patent was assigned to Wockhardt Limited and issued on May 25, 2010. Based on its earliest priority date and the standard 20-year US patent term, the patent’s ordinary term reached expiration in 2025, subject to any patent-term adjustment or other listed term events shown in the USPTO record.[1]

The claims are directed to beta-lactamase inhibitor chemistry rather than to an FDA-approved drug product. No established Orange Book-listed product appears to be associated with US 7,687,488. The patent’s principal commercial value was therefore prospective: it sought to protect a new beta-lactamase inhibitor platform for use with penicillins, cephalosporins, carbapenems, aminoglycosides, and related antibacterial agents.

What compounds does US Patent 7,687,488 protect?

The patent protects penam compounds with a 2-substituted methyl group attached to a heterocyclic ring system. The disclosed compounds contain the characteristic penam bicyclic beta-lactam-thiazolidine framework, with extensive oxidation at the sulfur-containing portion of the core.

The principal structural elements are:

Claim element	Scope
Core	Penam framework
Position of substitution	2-substituted methyl group
Heterocycle	Five- or six-membered heterocyclic ring
Ring atom variation	A is carbon or nitrogen
Carboxyl group	Free carboxylate, protected acid, or pharmaceutically acceptable salt
R2 and R3	Hydrogen, halogen, amino, protected amino, alkyl, alkenyl, or alkynyl groups
R substituent	Alkyl, alkenyl, aryl, aralkyl, cycloalkyl, oxo, heterocyclyl, or heterocyclylalkyl
Stereochemistry	Tautomers, stereoisomers, and pharmaceutically acceptable salts
Pharmaceutical protection	Single-agent compositions and combinations with antibiotics

The most commercially relevant compounds in the claims are substituted 1,2,3-triazolium derivatives. Claim 6 identifies examples containing methyl, ethyl, n-propyl, allyl, benzyl, amino-oxoethyl, tert-butoxycarbonylmethyl, morpholinylcarbonylmethyl, and related side chains.

These compounds are structurally distinct from the principal approved beta-lactamase inhibitor classes:

• Penicillanic acid sulfone inhibitors, such as sulbactam and tazobactam.
• Diazabicyclooctane inhibitors, such as avibactam and relebactam.
• Cyclic boronate inhibitors, such as vaborbactam.
• Other investigational non-beta-lactam inhibitors, including taniborbactam, nacubactam, xeruborbactam, and related compounds.

The patent’s claims should not be read as automatically covering these competing inhibitors. Structural infringement would depend on whether a competing molecule satisfies every limitation of an asserted claim.

How broad is independent claim 1?

Claim 1 is the principal composition-of-matter claim. It uses a Markush structure to cover a large chemical genus rather than one commercial compound.

Its scope has four important dimensions.

Broad substituent coverage

The R group extends across:

• Linear and branched alkyl groups.
• Alkenyl and alkynyl groups.
• Aryl and aralkyl groups.
• Cycloalkyl groups.
• Heterocyclyl and heterocyclylalkyl groups.
• Oxo-substituted structures.

This language can encompass simple alkyl groups, aromatic substituents, amino-acid-like side chains, amide-containing groups, ester-containing groups, and heterocyclic appendages.

Heterocycle coverage

The heterocycle language covers a wide range of nitrogen-, oxygen-, and sulfur-containing rings. Claim 5 lists pyrroles, imidazoles, pyrazoles, pyridines, pyrimidines, triazoles, tetrazoles, oxadiazoles, thiadiazoles, indoles, benzimidazoles, quinolines, and related fused or nonfused systems.

Claim 5 is important because it narrows the broad functional language of claim 1 into a defined inventory of ring systems. A compound outside the listed ring families may still fall within claim 1 if it satisfies the broader “five- to six-membered heterocyclic ring” limitation, depending on the complete formula and claim construction.

Acid, salt, and stereochemical coverage

The claims expressly include:

• Free carboxylic acids.
• Carboxylate anions.
• Protected carboxylic acids.
• Pharmaceutically acceptable salts.
• Tautomers.
• Stereoisomers.

This drafting attempts to prevent a design-around based solely on changing the acid form, isolating a salt, or using a different tautomeric or stereochemical presentation of the same active structure.

Practical limitation

The claim text supplied for claim 1 omits the chemical drawing or complete formula. That drawing is essential to determine the exact point of attachment between the penam core, methyl linker, and heterocycle. The scope cannot be reduced reliably to the text-only Markush language without the full figure and specification.

What does claim 6 protect?

Claim 6 is a species claim. It identifies specific triazolium-substituted penam compounds, including:

• 3-Methyl triazolium derivatives.
• 3-Ethyl triazolium derivatives.
• 3-n-Propyl triazolium derivatives.
• 3-Allyl triazolium derivatives.
• Amino-oxoethyl derivatives.
• tert-Butoxycarbonyl-containing derivatives.
• Morpholine-containing derivatives.
• Ester- and amide-substituted derivatives.
• Benzyl-substituted derivatives.

The listed compounds share a heavily oxidized penam core described as containing the 4,4,7-trioxo-4-thia-1-azabicyclo[3.2.0]heptane framework. Claim 6 is materially narrower than claim 1 because it identifies individual compounds and side chains.

Species claims generally provide a stronger infringement position when the accused compound is expressly listed. They also present a narrower validity target because prior art can be compared against the specific structures rather than against the full Markush genus.

The claim text contains apparent typographical inconsistencies, including “4,4,7-troxo” and “3-[2(” style formatting defects in some compound names. Such errors do not necessarily invalidate a claim. Their effect depends on whether a skilled chemist can identify the intended structure from the specification, examples, drawings, and prosecution record.

How do claims 7 through 8 protect manufacturing?

Claims 7 and 8 cover a process for preparing the compounds by reacting a penam-containing intermediate with an alkylating reagent represented as R-X, where X is a halogen.

The claimed process includes:

1. A compound containing the penam and heterocyclic system.
2. An alkyl halide or related R-X reagent.
3. Optional use of a silylating agent.
4. Formation of the 2-substituted methyl penam product.

Claim 8 lists the silylating agents, including:

• Hexamethyldisilazane.
• Trimethylchlorosilane.
• Trimethylsilyl iodide.
• N,O-bis(trimethylsilyl)acetamide.
• MSTFA.
• BSTFA.
• Chlorosilane derivatives.
• Bis(trimethylsilyl)urea.
• Mixtures of the listed agents.

The process claims can create manufacturing risk even where a company’s final active ingredient is covered only weakly by a composition claim. A competitor could avoid these claims by using a different bond-forming sequence, a nonhalide electrophile, a different protecting strategy, or a process that does not use the claimed intermediate.

The process claims are unlikely to block every practical route to the claimed compounds. Their strength depends on whether the commercial synthesis uses the specific R-X alkylation and whether the silylating-agent limitations are present.

What pharmaceutical compositions and combination products are covered?

Claims 9 and 10 cover pharmaceutical compositions containing at least one claimed compound, with claim 10 expressly requiring a pharmaceutically acceptable carrier.

Claims 11 through 13 extend protection to combinations with antibiotic agents. The listed partners include:

• Penicillins, including piperacillin, ampicillin, amoxicillin, ticarcillin, and oxacillin.
• Cephalosporins, including ceftriaxone, cefotaxime, ceftazidime, cefepime, cefixime, cefpodoxime, and cefdinir.
• Carbapenems, including imipenem and panipenem.
• Aminoglycosides, including amikacin, gentamicin, and tobramycin.
• Monobactams, including aztreonam.

These combination claims reflect the conventional beta-lactamase inhibitor commercial model: restore or preserve the antibacterial activity of a partner beta-lactam by inhibiting bacterial beta-lactamases.

The claims do not automatically cover every product that contains a beta-lactam antibiotic and a beta-lactamase inhibitor. The combination must include a compound satisfying the relevant penam limitations.

What treatment method is covered by claim 14?

Claim 14 covers administering an effective amount of an antibiotic and a claimed compound to a mammal for treatment of bacterial infection.

The claim is broad as to:

• The mammalian patient.
• The bacterial infection.
• The antibiotic.
• Route of administration.
• Dosage regimen.
• Treatment setting.

Its practical enforceability depends on the underlying compound being within claim 1 and on the accused treatment using both the antibiotic and the claimed penam compound. A treatment involving avibactam, vaborbactam, relebactam, or tazobactam would not be covered merely because those products are beta-lactamase inhibitors.

When does US Patent 7,687,488 lose exclusivity?

Event	Date or status
Earliest priority	2004, according to the US patent record
US application publication	2006
US patent grant	May 25, 2010
Patent number	US 7,687,488 B2
Standard 20-year term	Reached in 2025, measured from the earliest effective nonprovisional filing date
Orange Book listing	No established listed product identified
Approved product tied to patent	None identified
Current commercial blocking value	Primarily historical unless a term adjustment or other enforceable right extended the term

A grant date does not establish the patent’s expiration date. US patent term is generally calculated from the earliest effective nonprovisional filing date, with adjustments for patent-term adjustment, patent-term extension, terminal disclaimers, and certain prosecution delays.[2]

The controlling date for a transaction or launch decision should be the USPTO Patent Center term and maintenance record. The patent was not a conventional New Drug Application patent listed against an approved small-molecule product in the manner of a principal Orange Book patent.

What is the Orange Book status of US 7,687,488?

US 7,687,488 does not appear to have an established Orange Book role. The Orange Book lists patents associated with approved drug products and their approved labeling, including composition, method-of-use, and certain formulation patents.[3]

The patent’s absence from the Orange Book has several consequences:

• It does not create an Orange Book-based Paragraph IV certification obligation for a generic applicant.
• It does not automatically trigger a 30-month stay under the Hatch-Waxman framework.
• It does not establish FDA-recognized exclusivity for a listed drug.
• It does not prevent an ANDA applicant from entering on the basis of the patent’s existence alone.

A patent may still be asserted under ordinary patent litigation theories even if it is not Orange Book listed. The absence of an Orange Book listing is therefore commercially significant but not equivalent to a judicial determination that the patent is unenforceable.

Were there Paragraph IV challenges or patent litigation?

No widely reported Paragraph IV litigation or major federal patent case is associated with US 7,687,488 in connection with an approved commercial product. That result is consistent with the patent’s apparent status as a platform and investigational chemistry patent rather than an Orange Book-listed product patent.

There is also no established settlement agreement publicly associated with a generic launch against this patent. The lack of a reported settlement reduces evidence of commercial enforcement but does not resolve validity, infringement, or prosecution-history issues.

How strong is the patent estate?

The patent has mixed strengths.

Estate component	Relative strength	Reason
Broad genus claim	Moderate to weak against strong prior art	Large Markush scope creates written-description and enablement exposure
Specific triazolium species	Stronger	Claim 6 identifies defined compounds
Salt and stereoisomer coverage	Moderate	Useful against form-based design-arounds
Combination claims	Moderate	Depends on use of the claimed compound with the listed antibiotic
Manufacturing claims	Moderate to weak	Vulnerable to alternative synthetic routes
Method-of-treatment claim	Moderate	Requires use of a covered compound
Commercial enforceability today	Limited	Standard term appears to have ended in 2025

The main validity questions would likely involve:

1. Anticipation by earlier penam sulfone or heterocyclic beta-lactamase inhibitor disclosures.
2. Obviousness of attaching substituted heterocycles to a penam core.
3. Written description support for the very broad Markush genus.
4. Enablement across the full range of heterocycles and R groups.
5. Definiteness of the formula and the relationship among A, Het, R, R1, R2, and R3.
6. Whether the specification provides sufficient biological data across the claimed genus.

The species claims would generally be less exposed to genus-wide enablement attacks if the examples disclose their preparation, characterization, and antibacterial or beta-lactamase inhibition data.

How does this patent compare with competing beta-lactamase inhibitor patents?

Inhibitor class	Representative products or programs	Relationship to US 7,687,488
Penicillanic acid sulfone	Sulbactam, tazobactam	Same broad beta-lactamase inhibitor field; different claimed chemistry
Diazabicyclooctane	Avibactam, relebactam	Different core and generally outside the penam claims
Cyclic boronate	Vaborbactam	Different boronate-based scaffold
Penam triazolium derivatives	Compounds expressly listed in US 7,687,488	Direct subject matter of the patent
Investigational broad-spectrum inhibitors	Taniborbactam, nacubactam, xeruborbactam	Generally separate chemistry and patent families

The patent’s landscape position was strongest against a competitor developing a penam-based, heterocycle-substituted beta-lactamase inhibitor. It was weaker against companies using a different molecular scaffold.

What generic launch risks exist?

For a conventional generic antibiotic, US 7,687,488 presented limited direct risk unless the generic product contained one of the claimed penam compounds or relied on a claimed combination.

The principal risks were greater for:

• A new beta-lactamase inhibitor product.
• A fixed-dose beta-lactam/penam inhibitor combination.
• A manufacturing process using the claimed alkylation route.
• A follow-on product using one of the expressly listed triazolium species.
• A product relying on a patented method of treating bacterial infection.

Because the apparent patent term reached its end in 2025, the present risk is primarily historical, term-dependent, and relevant to damages, diligence, prior-art analysis, and freedom-to-operate records rather than to a new long-term launch blockade.

Key Takeaways

• US 7,687,488 covers 2-substituted methyl penam compounds, especially triazolium-substituted penam derivatives.
• Claim 1 is a broad chemical genus claim with extensive Markush coverage.
• Claim 6 narrows the estate to specifically identified triazolium penam species.
• Claims 7 and 8 cover an alkylation-based manufacturing process using R-X reagents and optional silylating agents.
• Claims 9 through 13 cover pharmaceutical compositions and combinations with numerous beta-lactam antibiotics.
• Claim 14 covers treatment of bacterial infections using a claimed compound and an antibiotic.
• The patent is not known as an Orange Book-listed product patent.
• No major Paragraph IV challenge, settlement, or commercial litigation record is associated with the patent.
• The standard US patent term appears to have ended in 2025, subject to the official USPTO term calculation.
• The patent is most relevant to penam-based beta-lactamase inhibitor programs, not to avibactam-, vaborbactam-, or relebactam-based products.

FAQs

Does US 7,687,488 cover tazobactam?

Not automatically. Tazobactam is a penicillanic acid sulfone, but it must satisfy the specific 2-substituted methyl and heterocyclic limitations of the asserted claim. The patent’s disclosed triazolium-substituted structures are materially different from tazobactam.

Does the patent cover avibactam?

Avibactam has a diazabicyclooctane scaffold and is not ordinarily within the penam compound genus described in US 7,687,488.

Can a company manufacture a claimed compound using a different process?

Potentially. A different synthesis may avoid claims 7 and 8, but it would not avoid a valid composition claim covering the final compound.

Is a patent license needed for a compound listed in claim 6?

During the enforceable patent term, commercial manufacture, sale, or use of a listed compound would have required a freedom-to-operate analysis and potentially a license. The standard term appears to have ended in 2025, subject to the official USPTO record.

Does the patent provide regulatory exclusivity?

No. A patent and FDA regulatory exclusivity are separate rights. US 7,687,488 does not itself establish FDA approval, New Chemical Entity exclusivity, orphan-drug exclusivity, or Orange Book protection.

References

1. United States Patent and Trademark Office. (2010). US Patent No. 7,687,488 B2, 2-substituted methyl penam compounds.
2. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

Drugs Protected by US Patent 7,687,488

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Orchid Pharma	EXBLIFEP	cefepime hydrochloride; enmetazobactam	POWDER;INTRAVENOUS	216165-001	Feb 22, 2024		DISCN	Yes	No	7,687,488		Y	Y		USE OF EXBLIFEP (CEFEPIME AND ENMETAZOBACTAM) FOR TREATING COMPLICATED URINARY TRACT INFECTIONS (CUTI) INCLUDING PYELONEPHRITIS CAUSED BY DESIGNATED SUSCEPTIBLE MICROORGANISMS

International Family Members for US Patent 7,687,488

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Cyprus	1114927
Denmark	2046802
European Patent Office	2046802