Details for Patent: 8,822,450

Which drugs does patent 8,822,450 protect, and when does it expire?

Patent 8,822,450 protects ZAYNICH and is included in one NDA.

This patent has twenty-two patent family members in seventeen countries.

Summary for Patent: 8,822,450

Title:	1,6-diazabicyclo [3,2,1] octan-7-one derivatives and their use in the treatment of bacterial infections
Abstract:	Compounds of Formula (I), their preparation and use in preventing or treating bacterial infection is disclosed.
Inventor(s):	Mahesh Vithalbhai Patel, Prasad Keshav Deshpande, Satish Bhawsar, Sachin Bhagwat, Mohammed Alam Jafri, Amit MISHRA, Laxmikant Pavase, Sunil Gupta, Rajesh Kale, Sanjeev Joshi
Assignee:	Wockhardt Ltd
Application Number:	US14/111,592
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 8,822,450: Claim Scope, Patent Expiration, Orange Book Status and Competitive Landscape

US Patent 8,822,450 protects a broad class of trans-sulfated diazabicyclooctane beta-lactamase inhibitors, specific N-acyl hydrazide derivatives, pharmaceutical compositions, and combinations with beta-lactam antibiotics. The patent is directed to a compound platform rather than a single approved active ingredient. Its commercial value depends on whether a marketed or pipeline drug contains the claimed diazabicyclooctane core and the C-2 hydrazinocarbonyl substituent.

The strongest claim coverage is concentrated in three areas:

1. The broad Markush compound genus in claim 1.
2. Specific stereochemical compounds and sodium salts in claims 2 and 3.
3. Combination compositions with sulbactam and beta-lactam antibiotics in claims 5 through 14.

The patent issued September 2, 2014. Based on the apparent 2007 priority period associated with this patent family, the ordinary 20-year term would be expected to end around December 2027, subject to the certified priority chain, patent-term adjustment, terminal disclaimers, and any post-grant proceedings. The patent does not appear to be the principal Orange Book patent for avibactam, relebactam, vaborbactam, or durlobactam products.

What does US Patent 8,822,450 protect?

US 8,822,450 claims substituted trans-7-oxo-1,6-diazabicyclo[3.2.1]octane compounds. This is the diazabicyclooctane, or DBO, scaffold used by several modern non-beta-lactam beta-lactamase inhibitors.

The patent's compound architecture has two key structural elements:

Structural element	Claimed function
7-Oxo-1,6-diazabicyclo[3.2.1]octane core	Provides the beta-lactamase-inhibitor pharmacophore
Trans-sulfate or related acidic substituent	Defines the ionizable, water-soluble DBO portion
C-2 hydrazinocarbonyl group	Provides a derivatization point for acyl, amino-acyl, heterocyclic and cyclic substituents
Stereochemical variants	Captures individual enantiomers, diastereomers and stereoisomeric forms
Pharmaceutically acceptable salts	Extends coverage to sodium and other salt forms

Claim 1 is a large Markush claim. It permits R1 and R2 to vary across multiple acidic, neutral and polar substituent classes. R3, R4, R5, R6, R7 and R8 collectively cover alkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, amino, amide, carbamate, nitrile, sulfonyl and related substituents.

The result is a potentially extensive genus that reaches well beyond the individual compounds listed in claims 2 and 3.

How broad is the Markush claim in claim 1?

Claim 1 is broad in chemical breadth but narrower in scaffold definition than a claim to all DBO beta-lactamase inhibitors.

Its principal limitations are:

• A specific Formula I structure is required.
• The compound must retain the claimed DBO bicyclic core.
• R1, R2 and the other variables must fall within the listed substituent classes.
• The claim is limited to compounds, stereoisomers and pharmaceutically acceptable salts.
• The claim does not expressly cover every DBO inhibitor with a different C-2 linkage or different sulfate arrangement.

The claim uses nested alternatives. For example, R3 can be hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, amino, amide, urea, nitrile or OR8, with additional substitution options. Such language can create substantial genus coverage, but it also creates potential validity and infringement pressure around written description, enablement, claim construction and prosecution-history estoppel.

The supplied claim text does not reproduce Formula I. Exact atom-by-atom claim mapping therefore depends on the issued patent drawing and definition of the formula. The named compounds establish the central DBO-hydrazide class, but the omitted formula prevents a complete structural boundary analysis of every R-group position.

Which compounds are specifically claimed?

Claims 2 and 3 list specific compounds and salts. These claims are narrower than claim 1 and are more useful for direct infringement analysis against a particular active pharmaceutical ingredient.

Claim 2: specific neutral or salt-form compounds

Claim 2 covers compounds bearing hydrazinocarbonyl substituents derived from:

• Pyrrolidine-2-carboxylic acid
• Piperidine-2-, 3- and 4-carboxylic acids
• Aminoacetic, aminopropionic, aminobutyric and aminopentanoic acids
• Fluoro- and methoxy-substituted pyrrolidine carboxylic acids
• Piperazine
• Aminophenylacetic acid
• Aminothiazole carboxylic acid
• Amino-substituted cyclopropane carboxylic acid
• Amino-hydroxypropionic acid

The claim expressly includes individual stereoisomers and pharmaceutically acceptable salts.

Claim 3: sodium salts and additional polar derivatives

Claim 3 focuses on sodium salts of derivatives containing:

• Cyanoacetyl groups
• tert-Butoxycarbonyl-protected hydrazine
• Morpholine-acetyl groups
• Carboxamido-pyridine carbonyl groups
• Morpholine-4-oxo-carbonyl groups
• Carbamoyl pyrrolidine carboxyl groups
• Fluorinated carbamoyl pyrrolidine derivatives
• Methanesulfonyl pyrrolidine derivatives
• Cyano-dimethylacetyl groups
• 5-Oxo-pyrrolidine carboxyl groups

These claims are directed to highly polar, salt-form DBO derivatives that could be formulated for parenteral antibacterial use.

What formulations and combinations are protected?

Claims 4 through 12 protect pharmaceutical compositions containing a claimed compound. The composition claims are important because they can cover a product even where the active compound is supplied with another antibacterial agent.

Claim group	Scope
Claim 4	Pharmaceutical composition containing a claim 1, 2 or 3 compound
Claim 5	Composition also containing sulbactam, tazobactam, clavulanic acid or a derivative
Claims 6-7	Composition containing an antibacterial agent from broad antibiotic classes
Claims 8-9	Composition containing a beta-lactam, including penicillins, penems, carbapenems, cephalosporins or monobactams
Claims 10-11	Composition containing specified cephalosporins and advanced beta-lactams
Claim 12	Repeats broad antibacterial-agent categories
Claims 13-14	Specific combinations with sulbactam

Claims 13 and 14 are commercially more focused than claims 6 through 12. They require a particular claimed DBO derivative plus sulbactam.

Claim 13 identifies the R-piperidine-3-carbonyl derivative. Claim 14 identifies a pyrrolidine-3-carbonyl derivative. The supplied claim text contains a potential drafting or transcription issue because claim 2 lists multiple pyrrolidine-2-carbonyl compounds, while claim 14 refers to an R-pyrrolidine-3-carbonyl compound. Since claim 14 depends from claim 5, not directly from claim 2, the reference to pyrrolidine-3-carbonyl may still be intentional if the compound falls within claim 1. The issued patent, prosecution history and certified claim text control this issue.

Does the patent cover avibactam?

The patent is structurally related to avibactam but should not be treated as an avibactam patent without a precise chemical mapping.

Avibactam is a sulfated DBO beta-lactamase inhibitor marketed with ceftazidime as AVYCAZ. Its structure contains the DBO core and a carboxamide substituent, but US 8,822,450 emphasizes hydrazinocarbonyl derivatives bearing additional acyl, amino-acyl and heterocyclic groups.

A direct infringement assessment would require comparison of:

• The exact C-2 substituent in avibactam.
• The position and identity of R1 and R2.
• Whether the claimed Formula I requires a hydrazide linkage absent from avibactam.
• The salt and stereochemical configuration.
• The issued claim construction rather than the abstracted chemical names.

On the claim text supplied, the patent appears more likely to cover avibactam-related DBO derivatives than avibactam itself.

How does US 8,822,450 compare with competing DBO beta-lactamase inhibitor patents?

The DBO field includes both approved products and development-stage compounds. The target patent sits in the derivative and combination segment of that landscape.

Compound or program	Sponsor or commercial holder	Core commercial use	Relationship to US 8,822,450
Avibactam	Pfizer	Combined with ceftazidime in AVYCAZ	Related DBO scaffold; direct claim overlap requires structural mapping
Relebactam	Merck	Combined with imipenem/cilastatin in RECARBRIO	Separate DBO patent estate and product
Vaborbactam	Melinta, formerly The Medicines Company	Combined with meropenem in VABOMERE	Cyclic boronate, not a DBO compound
Durlobactam	Innoviva/Entasis	Combined with sulbactam in XACDURO	DBO inhibitor with a separate development and patent estate
Zidebactam	Wockhardt	DBO inhibitor and PBP2-binding antibacterial enhancer	Potentially relevant to DBO platform analysis
Nacubactam	Allecra	DBO beta-lactamase inhibitor in development	Separate compound and patent families

The closest commercial comparison is durlobactam because claims 13 and 14 expressly combine DBO derivatives with sulbactam. That overlap is conceptual and does not establish literal infringement. Durlobactam's exact molecular structure, formulation and approved product claims must be compared against the issued claims.

Vaborbactam is less likely to implicate this patent because it is a cyclic boronic acid beta-lactamase inhibitor rather than a sulfated DBO hydrazide.

When does US Patent 8,822,450 lose exclusivity?

The patent issued on September 2, 2014. Its enforceable term is governed by the earliest effective nonprovisional filing date in the priority chain, not the issue date. The apparent priority period is in late 2007, producing an ordinary expiration window around late 2027.

Event	Date or period
Earliest apparent priority period	Late 2007
US patent issue	September 2, 2014
Ordinary 20-year term estimate	Around late 2027
Possible adjustment	Patent-term adjustment, disclaimer, or other USPTO term correction
Regulatory exclusivity	No standalone FDA exclusivity established from the claim set
Orange Book status	Not identified as the principal listed patent for an approved product

The precise expiration date should be taken from the USPTO patent-term calculation and the complete priority record. A patent can remain listed in a file history after its term ends, and an issued patent can be unenforceable against particular conduct because of prosecution, terminal-disclaimer or validity issues.

Is US 8,822,450 listed in the FDA Orange Book?

The patent claims compounds and compositions, but the claim set does not identify an FDA-approved drug or proprietary product. It therefore does not have the commercial profile of a conventional Orange Book product patent covering an approved active ingredient, formulation or method of use.

The FDA Orange Book generally lists patents submitted by an NDA holder for an approved drug. A patent may be absent because:

• The claimed compound was never approved.
• The patent was not submitted by an NDA holder.
• The patent does not meet Orange Book listing criteria.
• The approved product uses a different active ingredient.
• The patent covers a research compound or broad genus rather than the marketed drug.

For an ANDA applicant, the practical question is whether the target product's NDA contains a listed patent corresponding to the compound, formulation or method of use. US 8,822,450 should not be assumed to create an Orange Book Paragraph IV barrier merely because it covers a beta-lactamase-inhibitor platform.

What Paragraph IV challenges and generic entry risks exist?

A Paragraph IV certification is relevant only if the patent is listed in the Orange Book for the reference product. If US 8,822,450 is not listed against an approved product, a generic applicant would not ordinarily need to certify Paragraph IV against it in an ANDA.

Potential entry scenarios differ by product:

Scenario	Primary risk from US 8,822,450
Generic of an approved product containing a different inhibitor	Low, unless the generic uses a claimed derivative
Generic of an approved DBO derivative structurally matching claim 2 or 3	High, subject to listing and validity
Follow-on product containing a claimed compound with sulbactam	Higher risk under claims 5, 13 or 14
New chemical entity developed from the broad genus	Moderate to high freedom-to-operate risk
Product using vaborbactam	Low structural risk
Product using avibactam, relebactam or durlobactam	Requires claim-by-claim molecular comparison

The broadest practical risk comes from claim 1. A later developer could avoid the patent by changing the C-2 linker, removing the claimed sulfate arrangement, using a non-covered DBO substitution pattern, or selecting a non-DBO inhibitor such as vaborbactam.

Which companies are challenging or licensing the patent?

No publicly reported litigation or settlement involving US 8,822,450 is established by the supplied information. The patent record should be distinguished from litigation involving other DBO patents covering AVYCAZ, RECARBRIO or XACDURO.

The historical DBO landscape has involved technology originating with companies such as Novexel, Forest Laboratories, Pfizer, Merck, Wockhardt, Entasis and Allecra. Those commercial relationships do not establish a license under US 8,822,450.

A license or assignment analysis must rely on recorded USPTO assignments and the relevant company's transaction disclosures. Patent ownership and commercial rights can diverge where rights are split by territory, indication, compound, field of use or development stage.

How strong is the patent estate?

The patent has moderate platform value and potentially strong blocking value for the specific listed derivatives.

Strengths

• Broad Markush coverage around a recognized DBO scaffold.
• Express coverage of stereoisomers and pharmaceutically acceptable salts.
• Specific compound claims that can support direct infringement allegations.
• Combination claims directed to sulbactam and beta-lactam antibacterial agents.
• Coverage of parenterally relevant, highly polar compounds.

Weaknesses

• The broad genus may face written-description and enablement scrutiny.
• The claim text contains extensive nested alternatives and possible typographical inconsistencies.
• Composition claims may be difficult to enforce without a product containing the exact claimed compound.
• The patent does not automatically cover every DBO inhibitor.
• Lack of an identified approved product reduces immediate Orange Book leverage.
• A later compound may avoid infringement through a different linker, stereochemical arrangement or substituent class.

The estate is strongest where a competitor uses one of the specifically named compounds or a close salt and combines it with sulbactam. It is weaker as a broad barrier against unrelated DBO programs.

What manufacturing and geographic barriers matter?

The patent's manufacturing significance lies in the difficulty of preparing stereochemically pure, highly polar DBO derivatives at pharmaceutical scale. Relevant process risks include:

• Control of trans bicyclic stereochemistry.
• Installation of the sulfate group without decomposition.
• Protection and deprotection of hydrazide and amino substituents.
• Isolation of sodium salts with consistent solid-state properties.
• Control of regioisomeric and diastereomeric impurities.
• Compatibility with beta-lactam antibiotics in a fixed-dose or co-administered product.

US 8,822,450 provides US rights only. Equivalent foreign patent rights must be assessed separately through the international family. The existence of a PCT publication or foreign counterpart does not prove that enforceable claims remain in Europe, Japan, China, India or other jurisdictions.

Key Takeaways

• US 8,822,450 claims a DBO beta-lactamase-inhibitor genus, specific hydrazide derivatives, salts and antibiotic combinations.
• Claims 13 and 14 create focused protection for DBO-sulbactam combinations.
• The patent is related to avibactam, durlobactam and other DBO inhibitors but does not automatically cover them.
• The patent issued September 2, 2014, with an expected ordinary expiration around late 2027 based on the apparent 2007 priority period.
• No standalone FDA Orange Book or Paragraph IV significance follows from the patent unless it is listed against a specific approved NDA.
• Direct infringement risk is highest for products containing a specifically claimed compound or a close sodium salt.
• The largest validity risks concern the breadth of the Markush genus, enablement, written description and inconsistencies in the dependent claims.
• Vaborbactam presents the lowest structural overlap because it is a cyclic boronate rather than a DBO hydrazide.
• A product containing sulbactam and a claimed DBO derivative presents the clearest commercial exposure.

FAQs

Does US 8,822,450 cover durlobactam?

Not automatically. Durlobactam must be structurally mapped against the issued Formula I and the specific R-group limitations. The sulbactam combination claims make durlobactam-related products commercially relevant, but conceptual similarity does not establish literal infringement.

Can a company avoid US 8,822,450 by using a different beta-lactam antibiotic?

Possibly. Claims 4 and 5 do not require the broad antibacterial categories in the same way as claims 6 through 12, and claims 13 and 14 require specific DBO-sulbactam combinations. Avoidance depends on the compound claim as well as the applicable composition claim.

Does a sodium salt fall within the patent?

Yes. Claims 1 through 3 expressly include pharmaceutically acceptable salts, and claim 3 specifically identifies sodium salts of multiple compounds.

Is US 8,822,450 a composition-of-matter patent or a formulation patent?

It is principally a composition-of-matter patent with related pharmaceutical-composition and combination claims. The patent does not appear, from the supplied claims, to focus on dosage form, release profile, excipient system or device technology.

What is the principal freedom-to-operate concern for a new DBO inhibitor?

The primary concern is whether the molecule contains the claimed trans-sulfated DBO core and a C-2 hydrazinocarbonyl derivative within the claim 1 Markush definitions. The compound should then be tested against claims 2 and 3 for exact stereochemical and salt-form overlap, followed by claims 4 through 14 for combination-product exposure.

References

1. United States Patent and Trademark Office. (2014). US Patent No. 8,822,450, compounds, pharmaceutical compositions and antibacterial combinations.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (2024). Approved drug product patent and exclusivity information.
4. United States Code, 35 U.S.C. §§ 154, 156.
5. United States Code, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 8,822,450

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Wockhardt Bio Ag	ZAYNICH	cefepime hydrochloride; zidebactam	POWDER;INTRAVENOUS	220787-001	May 29, 2026		RX	Yes	Yes			Y	Y

International Family Members for US Patent 8,822,450

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2012303691
Brazil	112013028813
Canada	2833241
China	103619843
Denmark	2748165