Details for Patent: 8,487,093

Which drugs does patent 8,487,093 protect, and when does it expire?

Patent 8,487,093 protects RECARBRIO and is included in one NDA.

This patent has seventy-four patent family members in thirty-eight countries.

Summary for Patent: 8,487,093

Title:	β-lactamase inhibitors
Abstract:	Substituted bicyclic beta-lactams of Formula I: (I), are β-lactamase inhibitors, wherein a, X, R1 and R2 are defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with β-lactam antibiotics. In particular, the compounds can be employed with a β-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to β-lactam antibiotics due to the presence of the β-lactamases.
Inventor(s):	Timothy A. Blizzard, Helen Chen, Candido Gude, Jeffrey D. Hermes, Jason Imbriglio, Seongkon Kim, Jane Y. Wu, Christopher J. Mortko, Ian Mangion, Nelo Rivera, Rebecca T. Ruck, Michael Shevlin
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US12/812,763
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,487,093
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 8,487,093: Scope, Claim Architecture, and US Patent Landscape

What does US 8,487,093 claim cover?

US Patent 8,487,093 claims a class of sulfooxy-containing bicyclic carboxamides defined by a Formula I Markush structure, followed by narrow dependent claim sets that lock specific substituents, stereochemical variants, salt forms, and crystal form (monohydrate). It also claims pharmaceutical compositions and combination regimens with beta-lactam antibiotics, with imipenem and cilastatin called out in later dependencies.

Core claim scaffold (Claim 1, Formula I)

Claim 1 is the broadest molecule claim and defines:

• A compound of Formula I or a pharmaceutically acceptable salt
• With a variable linker: X is
  • CH2, or
  • CH2CH2
• With an amide substituent:
  • R1 is C(O)N(R3)R4
• With a sulfonamide/sulfonyloxy-like functional group set:
  • R2 is:
    SO3M, OSO3M, SO2NH2, PO3M, OPO3M, CH2CO2M, CF2CO2M, or CF3
• With counterion/charge handling:
  • M is H or a pharmaceutically acceptable cation
• With amide N substituents:
  • R3 is HetA
  • R4 is H,
    or alternatively R3 and R4 together with the N atom form a heterocyclyl group
• The HetA ring is a 4- to 9-membered heterocycle containing 1 or 2 N atoms, saturated or mono-unsaturated, optionally fused and substituted with defined groups:
  • HetA is optionally fused with a C3-7 cycloalkyl
  • The optionally fused ring is optionally substituted with 1 to 2 substituents selected from:
  • N(RA)RB, and/or
  • (CH2)nRC
  • With constraints:
  • each n is 0, 1, 2, or 3
  • RA is H or C1-8 alkyl
  • RB is H or C1-8 alkyl
  • RC is C1-6 alkyl, OH, O-C1-8 alkyl, halogen pyridyl, pyrrolidinyl, or piperidinyl

Claim narrowing steps

From Claim 2 onward the patent reduces dimensionality by selecting specific R2 values, narrowing HetA exemplars, and then enumerating specific stereochemical compounds.

Claim 2 narrows R2:

• R2 is OSO3M

Claim 3 narrows further:

• R2 is OSO3H

So the patent proceeds from broad ionizable functionality to a specific acidic sulfooxy motif.

HetA constraints (Claim 4)

Claim 4 narrows HetA to specific saturated heterocycles:

• optionally fused saturated heterocyclic ring selected from:
  • azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, azocanyl, azabicyclo[3.1.0]cyclohexyl
• optionally substituted with:
  • N(RA)RB
  • and/or 1 or 2 (CH2)nRC substituents

A second, enumerated substituent set using T and T′ (Claims 5 and 6)

Claims 5 and 6 provide another breadth-narrowing axis by specifying allowable values of T and T′ (substituent sets), then giving a dependent claim that fixes them to an even smaller set.

Specific exemplars and stereochemistry enumeration (Claims 7 to 12)

Claims 7, 8, 9, 10, and 11 enumerate concrete molecules, including diastereomer descriptors and multiple amino-heterocycle choices.

Across these:

• The bicyclic core is repeatedly:
  • 1,6-diazabicyclo[3.2.1]octane (and once 1,3-diazabicyclo[2.2.1]heptane)
• The substituent is consistently a:
  • sulfooxy group on the bicyclic core (named “(sulfooxy)”)
• The amide/carboxamide is named as:
  • carboxamide or carboxylic acid acid form in one enumerated example
• Stereochemistry is fixed in many exemplars using (2S,5R) (and in some cases additional centers)

Claim 12 adds a solid-state qualifier:

• The compound is (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
• and is in the form of a crystalline monohydrate

This is one of the patent’s highest-value enforcement levers because it targets a specific physical form.

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What drug/therapeutic area does the patent cover?

The patent is aimed at bacterial infection treatment via a combination mechanism with beta-lactam antibiotics.

Composition claims

• Claim 13: pharmaceutical composition
  • compound of Claim 1 (or salt) + pharmaceutically acceptable carrier
• Claim 14: composition further comprises a beta-lactam antibiotic

Method claims (therapeutic use)

• Claim 15: method for treating bacterial infection
  • administer therapeutically effective amount of compound of Claim 1
  • optionally in combination with beta-lactam antibiotic

Specific combination stack with imipenem and cilastatin

The patent then defines a set of more concrete downstream combination claims:

• Claim 16: specifies a particular compound:
  • (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
• Claim 18: composition further comprises beta-lactam antibiotic
• Claim 19: beta-lactam antibiotic is imipenem
• Claim 20: composition further comprises cilastatin
• Claim 21: method treating bacterial infection using compound of Claim 16 in combination with beta-lactam antibiotic
• Claim 22: beta-lactam antibiotic is imipenem
• Claim 23: further comprises administering cilastatin

This creates an enforceable claim chain for a specific clinical regimen:

• active adjuvant (the claimed sulfooxy bicyclic carboxamide) + imipenem + cilastatin

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Where are the patent’s enforcement choke points?

US 8,487,093 contains three distinct “choke points” that typically drive freedom-to-operate and claim charting.

1) The Markush coverage is broad, but meaningful enforcement narrows fast

Claim 1 covers multiple R2 variants and a HetA ring class, but practical enforcement often hinges on the R2 and HetA definitions you actually plan to commercialize. The patent then tightens to:

• R2 = OSO3M (Claim 2)
• R2 = OSO3H (Claim 3)
• HetA selected from a defined saturated ring list (Claim 4)
• and ultimately enumerated specific stereochemical examples (Claims 7 to 11)

2) Solid-state targeting: crystalline monohydrate (Claim 12)

If a product is sold as a crystalline monohydrate, Claim 12 is directly relevant. If a competitor uses a different hydrate level or amorphous form, the Claim 12 infringement case changes materially.

3) Combination regimen targeting: imipenem + cilastatin (Claims 19 to 23)

The patent’s combination claims are not generic “beta-lactam + adjuvant.” It calls out imipenem and cilastatin, which:

• increases the specificity of infringement mapping
• supports enforcement against label-matched regimens

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Claim-by-claim scope map (practical reading)

Molecular claims

Claim	Scope element	What it locks in
1	Formula I Markush	X (CH2/CH2CH2), R1 (C(O)N(R3)R4), R2 options (incl. OSO3M/OSO3H), HetA ring class, salt permitted
2	Dependent	R2 = OSO3M
3	Dependent	R2 = OSO3H
4	Dependent	HetA ring list (azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, azocanyl, azabicyclo[3.1.0]cyclohexyl) with optional substitutions
5-6	Dependent	Specific allowable T/T′ substituent sets (with Claim 6 narrower lists)
7	Dependent	Enumerated stereochemically defined sulfooxy bicyclic carboxamides
8	Dependent	Extended enumerated stereochemically defined set including diastereomer descriptors
9-11	Dependent	Narrower subsets and single-member exemplars
12	Dependent	The Claim 11 compound as a crystalline monohydrate

Product and use claims

Claim	Scope element	What it locks in
13	Composition	Compound (Claim 1) + carrier
14	Composition	Composition further contains a beta-lactam antibiotic
15	Method	Treat bacterial infection with compound (Claim 1) +/- beta-lactam
16-17	Molecular + composition	Specific compound + composition
18-20	Combination composition	Beta-lactam is imipenem (Claim 19) and further cilastatin (Claim 20)
21-23	Combination method	Method with imipenem (Claim 22) and cilastatin (Claim 23)

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Patent landscape in the US: what can be concluded from the claim text provided

No publication dates, assignee names, priority data, prosecution history, expiration terms, related family members, or cited references were provided. Without those elements, a complete US landscape (competitors, continuations, enforcement status, or remaining claim term) cannot be produced from Claim 1-23 text alone.

What can be stated strictly from the claim content is the likely landscape position inside a US portfolio:

1. Scope maturity: the patent is structured with:

   • a broad genus (Claim 1)
   • followed by dense exemplification (Claims 7-11)
   • and a single, high-value solid-state form (Claim 12)
   • plus downstream product-use claims that match a known clinical combination use case (imipenem + cilastatin)

2. Portfolio strategy signal: enumerated stereochemistry and monohydrate inclusion indicates the patent likely overlaps with:

   • a marketed or development-stage compound series
   • and associated solid-form development

3. Enforcement posture signal: the presence of imipenem + cilastatin in method and composition claims suggests the portfolio is designed to capture:

   • combination therapy regimens
   • rather than only stand-alone use

These are landscape-relevant signals, but they do not replace a family-level search or a claims-expiration mapping.

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Key takeaways

• US 8,487,093 has a Formula I Markush genus claim (Claim 1) covering sulfooxy-containing bicyclic carboxamide scaffolds with variable amide N substituents (HetA) and R2 functionality.
• The patent rapidly narrows to R2 = OSO3M (Claim 2) and R2 = OSO3H (Claim 3), then tightens HetA to specific heterocycles (Claim 4).
• Highest enforcement leverage points are:
  • crystalline monohydrate in Claim 12
  • and combination therapy targeting imipenem and cilastatin in Claims 19-23.
• The molecular claims use dense stereochemical enumeration (Claims 7-11), which supports tight claim charts against specific candidates.

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FAQs

1) Is Claim 1 a pure chemical Markush claim or does it already reflect the sulfooxy motif used later?

Claim 1 includes R2 options that include sulfooxy-related groups (including OSO3M and OSO3H through dependent narrowing), and it permits salts. The sulfooxy motif becomes explicit in dependent claims 2 and 3.

2) What makes Claim 12 unusually commercially important compared with the genus?

Claim 12 adds a form restriction: the specified compound is a crystalline monohydrate. That physical-form limitation can materially affect infringement if a competitor uses a different solid form.

3) Do the method claims cover any beta-lactam or are they narrowed to specific drugs?

They start broadly with “beta-lactam antibiotic” (Claim 14 and Claim 15), then narrow in later dependent claims to imipenem (Claims 19 and 22) and further include cilastatin (Claims 20 and 23).

4) Does the patent claim only stand-alone therapy?

No. It claims compositions and methods where the compound is administered in combination with beta-lactam antibiotics, and it specifies the imipenem + cilastatin combination in downstream claims.

5) If a candidate differs in HetA but keeps the same bicyclic core, is it still covered?

Claim 1 covers a class of HetA heterocycles defined by ring size, saturation/unsaturation, and substitution constraints. Coverage depends on whether the candidate’s HetA falls within the defined HetA parameters and whether later enumerated dependent claims are directly matched.

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References

1. United States Patent No. 8,487,093. Claims 1-23 (provided in prompt text).

Drugs Protected by US Patent 8,487,093

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Msd Merck Co	RECARBRIO	cilastatin sodium; imipenem; relebactam	POWDER;INTRAVENOUS	212819-001	Jul 16, 2019		RX	Yes	Yes	8,487,093		Y	Y		TREATMENT OF COMPLICATED INTRA-ABDOMINAL INFECTIONS (CIAI)
Msd Merck Co	RECARBRIO	cilastatin sodium; imipenem; relebactam	POWDER;INTRAVENOUS	212819-001	Jul 16, 2019		RX	Yes	Yes	8,487,093		Y	Y		TREATMENT OF HOSPITAL-ACQUIRED BACTERIAL PNEUMONIA AND VENTILATOR-ASSOCIATED BACTERIAL PNEUMONIA (HABP/VABP)
Msd Merck Co	RECARBRIO	cilastatin sodium; imipenem; relebactam	POWDER;INTRAVENOUS	212819-001	Jul 16, 2019		RX	Yes	Yes	8,487,093		Y	Y		TREATMENT OF COMPLICATED URINARY TRACT INFECTIONS, INCLUDING PYELONEPHRITIS (CUTI)

Foreign Priority and PCT Information for Patent: 8,487,093

PCT Information
PCT Filed	January 15, 2009	PCT Application Number:	PCT/US2009/031047
PCT Publication Date:	July 23, 2009	PCT Publication Number:	WO2009/091856

International Family Members for US Patent 8,487,093

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2231667		301050	Netherlands
European Patent Office	2666774		301052	Netherlands
European Patent Office	2666774		301051	Netherlands
European Patent Office	2231667		LUC00165	Luxembourg
European Patent Office	2231667		PA2020516	Lithuania
European Patent Office	2231667		122020000034	Germany
European Patent Office	2231667		2020C/522	Belgium