United States Patent 8,247,402: Doripenem Crystal Form Scope, Patent Expiration, and Competitive Landscape

U.S. Patent No. 8,247,402 protects a defined monohydrate crystal of doripenem, the active ingredient in Doribax. Its principal limitation is structural and analytical: infringement requires the claimed doripenem monohydrate crystal and a powder X-ray diffraction pattern containing the specified peaks. The patent also covers medicaments containing that crystal, powder-filling preparations, a crystallization and selection process, and preparation of injectable solutions.

The patent’s nominal term runs to December 28, 2027, subject to any recorded patent-term adjustment or extension. The patent is a solid-form patent, not a broad composition-of-matter patent. Its commercial value therefore depends on whether a generic or alternative manufacturer uses the claimed monohydrate, produces it during manufacturing, or markets a drug product containing it.

What drug and crystal form does U.S. Patent 8,247,402 protect?

The protected active ingredient is doripenem, a carbapenem antibacterial marketed in the United States as Doribax by Shionogi and later associated with Johnson & Johnson subsidiaries for U.S. commercialization.

The claims identify doripenem by its full stereochemical chemical name:

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3S,5S)-5-(sulfamoylaminomethyl)pyrrolidin-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.

The patent does not claim doripenem in every physical form. It claims a monohydrate crystal characterized by a specified powder X-ray diffraction, or PXRD, profile. The form is therefore a polymorph or crystalline-hydrate claim directed to the solid-state identity of doripenem.

The key independent product claim requires:

Doripenem;
A monohydrate;
A crystalline form;
PXRD peaks at approximately 13.04, 14.98, 15.88, 16.62, 20.62, 21.06, 22.18, 23.90, 26.08, 28.22, and 28.98 degrees 2θ;
Cu Kα radiation;
A 1.34 Å monochromator;
Tube voltage of 40 kV; and
Tube current of 40 mA.

The claim uses “comprising,” so the listed peaks are required but do not necessarily exclude additional peaks. The term “about” introduces ordinary analytical tolerance, but the patent’s specification, examples, instrument conditions, and expert evidence would determine the practical boundaries.

How many claims does U.S. Patent 8,247,402 contain?

The supplied claim set contains five claims. Claim 1 is the principal crystal claim. Claims 2 and 3 extend the protection to pharmaceutical preparations. Claim 4 covers a manufacturing process. Claim 5 covers preparation of an injectable solution.

Claim	Claim category	Principal limitation
1	Crystal form	Doripenem monohydrate with specified PXRD peaks
2	Medicament	Solid-form medicament containing the claimed crystal and pharmaceutical ingredients
3	Dosage form	Powder-filling preparation under claim 2
4	Manufacturing process	Aqueous dissolution, crystallization, PXRD selection, and drying
5	Preparation method	Dissolving the crystal or medicament in a physiologically acceptable agent to make an injectable solution

Claims 2 through 5 are narrower than a general claim to doripenem. They depend on the claimed crystal or incorporate its PXRD limitation.

What is the scope of claim 1 covering the doripenem monohydrate crystal?

Claim 1 is a product-by-characterization claim. It defines the product through its PXRD pattern rather than through a complete set of conventional solid-state parameters such as unit-cell dimensions, space group, water content, thermal transitions, or infrared spectrum.

A product is most likely within claim 1 if analytical testing shows:

The material is doripenem;
The material is a monohydrate;
It is crystalline; and
Its PXRD pattern includes the claimed peaks under materially comparable measurement conditions.

The claim does not expressly require:

A particular particle-size distribution;
A particular morphology;
A particular bulk density;
A particular residual-solvent level;
A particular purity threshold;
A specific pharmaceutical excipient;
A specific dosage strength; or
A specific route of administration.

Those omissions broaden the claim within the identified crystal form. They also leave room for disputes over mixtures, partial hydration, amorphous content, peak shifts, preferred orientations, and instrument-to-instrument variability.

A generic manufacturer could attempt to avoid claim 1 by developing a genuinely different doripenem solid form, such as an anhydrous form, another hydrate, an amorphous form, or a salt. That strategy would require confirmation that the alternative does not convert to the patented monohydrate during isolation, storage, formulation, sterilization, or reconstitution.

What does claim 2 protect in a doripenem drug product?

Claim 2 covers a medicament containing the claimed crystal in solid form together with one or more pharmaceutically acceptable ingredients.

The claim reaches beyond the isolated active pharmaceutical ingredient. It can cover a formulated product if the doripenem component retains the claimed crystal identity. The relevant product questions are:

Is doripenem present as the claimed monohydrate crystal?
Does the finished solid product contain the required PXRD signature?
Are the excipients pharmaceutically acceptable?
Does the formulation remain crystalline during storage?

Claim 2 does not appear limited to a particular excipient system, container, strength, or labeling statement. Its practical reach may therefore include multiple solid pharmaceutical presentations, subject to proof that the claimed crystal remains present.

For an injectable carbapenem, the product may be supplied as a sterile powder for reconstitution rather than as a ready-to-inject liquid. Claim 2 is directed to the solid medicament, while claim 5 addresses preparation of the injectable solution.

What formulation does claim 3 protect?

Claim 3 narrows claim 2 to a powder-filling preparation. This language is commercially relevant because doripenem injection products are commonly supplied as sterile powders that are reconstituted before administration.

The claim potentially covers a vial or similar container filled with a powder containing the claimed doripenem monohydrate crystal and acceptable pharmaceutical ingredients. The claim does not, based on the supplied text, require a particular vial, stopper, fill weight, reconstitution volume, or diluent.

The important infringement question is the solid-state condition at the point of manufacture and sale. A subsequent liquid reconstitution may not eliminate liability for a product claim that is infringed when the powder-filled product is made or sold.

What manufacturing process is protected by claim 4?

Claim 4 covers a process with five operational stages:

Dissolving doripenem or a doripenem hydrate in water;
Depositing crystals from the resulting aqueous solution;
Determining the PXRD pattern;
Selecting crystals with a specified PXRD pattern; and
Drying the selected crystals.

The process is narrower than claim 1 because it requires the specified manufacturing sequence. It also contains a notable textual inconsistency.

Claim 1 identifies peaks at:

13.04, 14.98, 15.88, 16.62, 20.62, 21.06, 22.18, 23.90, 26.08, 28.22, and 28.98 degrees 2θ.

Claim 4, step D, identifies a different set:

6.62, 13.04, 15.44, 16.58, 17.64, 20.88, 23.26, 25.02, and 25.52 degrees 2θ.

That difference is material. It may reflect a drafting error in the supplied claim text, a different crystal-selection criterion, or a translation issue. The issued patent’s official claim text and prosecution history control. On the text supplied, claim 4 should not automatically be treated as requiring the exact PXRD pattern of claim 1.

The process claim creates several potential non-infringement routes:

Crystallization from a solvent other than water;
Use of a process that does not include PXRD-based selection;
Selection by a different analytical method;
Use of a different crystal form;
Direct isolation without the claimed sequence; or
Manufacture outside the United States, subject to U.S. importation and contributory-infringement issues.

The final drying step may also matter. A process that produces the crystal but does not perform the claimed drying operation could present a claim-construction issue.

What does claim 5 cover for injectable doripenem?

Claim 5 covers a method of preparing an injectable solution by dissolving the claimed crystal or a medicament of claim 2 in a physiologically acceptable agent.

The claim is not limited, on the supplied wording, to a named diluent or a particular clinical administration method. “Physiologically acceptable agent” may encompass approved injectable diluents compatible with doripenem, but construction would depend on the patent specification and prosecution record.

The claim raises a practical distinction between:

Manufacturing a sterile injectable solution;
Reconstituting a powder immediately before administration; and
Administering the solution to a patient.

The supplied claim recites preparation of the solution, not administration to a patient. A generic applicant’s product and labeling would need to be assessed against the exact method steps and any induced-infringement theory.

When does U.S. Patent 8,247,402 expire?

The patent has a nominal expiration date of December 28, 2027, based on a claimed priority date of December 28, 2006 and the U.S. patent-term framework applicable to the patent family. The operative date should be confirmed against the USPTO patent record, including any patent-term adjustment, terminal disclaimer, or patent-term extension entry. (USPTO, n.d.-a)

Event	Date or status
Earliest priority date	December 28, 2006
U.S. patent	8,247,402
Issue date	August 21, 2012
Nominal expiration	December 28, 2027
Patent type	Crystal form, formulation, process, and injectable-preparation claims
PTE relevance	No PTE should be assumed for this crystal patent without a specific regulatory extension record
PTA relevance	Any USPTO-recorded adjustment would affect the final date

Doripenem’s regulatory exclusivity and the broader composition-of-matter estate are separate from the term of this crystal patent. The expiration of a foundational doripenem patent would not automatically invalidate a later-expiring crystal-form patent.

What is the FDA Orange Book status of doripenem and Patent 8,247,402?

Doribax was approved under NDA 021406 for injectable doripenem. The FDA later identified Doribax as discontinued from marketing, but discontinuation for commercial reasons does not by itself establish withdrawal for safety or efficacy reasons. (FDA, 2014)

The Orange Book analysis must distinguish three issues:

Whether NDA 021406 remains listed;
Whether Patent 8,247,402 is listed against that NDA; and
Whether an approved reference product is available for an ANDA pathway.

Orange Book patent listings are sponsor-submitted and product-specific. A patent may be relevant to a product yet absent from the Orange Book, particularly where the patent concerns a manufacturing process, a solid form, or a formulation not submitted as a required product characteristic. (FDA, n.d.-a)

For Patent 8,247,402, the most important regulatory point is that the claims are not limited to a method of treatment. Claims 1 through 3 are product and formulation claims, while claims 4 and 5 are process claims. If listed against the NDA, they could create a Paragraph IV certification issue. If not listed, they could remain enforceable outside the formal Orange Book certification framework.

Are Paragraph IV challenges possible against this patent?

Yes. A generic applicant could make a Paragraph IV certification if the patent is listed for the reference product and the applicant asserts that the patent is invalid, unenforceable, or will not be infringed. The Hatch-Waxman framework permits litigation following the required notice to the patent owner and NDA holder. (21 U.S.C. § 355)

Potential Paragraph IV positions include:

The claimed PXRD peaks do not distinguish a new crystal form from prior art;
The monohydrate crystal was anticipated;
The crystal form would have been obvious from known doripenem hydrates and crystallization methods;
The claim is indefinite because “about” does not provide a reliable boundary;
The analytical limitations are not sufficiently reproducible;
The accused product contains a different hydrate or polymorph;
The product claim is not infringed because the claimed crystal is absent from the commercial dosage form;
The process claim is avoided because the generic manufacturer uses a different crystallization or selection process; or
The patent is unenforceable based on prosecution conduct, if supported by the record.

Solid-form patents can be difficult to invalidate when the claimed form has demonstrable properties that were not predictable from the prior art. The strongest invalidity case would normally require prior-art disclosure of the same PXRD pattern or a persuasive showing that the claimed form was an expected result of routine experimentation.

Which companies are challenging doripenem exclusivity?

No reliable conclusion of a current Paragraph IV lawsuit or settlement involving U.S. Patent 8,247,402 follows from the claim text alone. The patent record, FDA listing data, and federal docket must be evaluated separately.

The competitive field consists of:

The original branded doripenem sponsor;
Generic injectable manufacturers;
Contract manufacturers capable of producing sterile carbapenem powders;
Suppliers controlling doripenem API and crystal-form technology; and
Potential licensees or technology partners holding alternative solid forms.

The absence of a known commercial generic does not prove that the patent estate is blocking entry. Doripenem faces technical barriers involving beta-lactam stability, sterile powder manufacture, reconstitution compatibility, impurity control, and supply-chain validation.

How strong is the patent estate for doripenem?

Patent 8,247,402 is strongest against a competitor that:

Uses doripenem monohydrate;
Produces the same PXRD profile;
Supplies a sterile powder containing that form; or
Uses the claimed aqueous crystallization and PXRD-selection process.

Its protection is weaker against a competitor that can reliably commercialize a different solid form without conversion to the patented monohydrate.

Risk area	Assessment
Same doripenem monohydrate	High risk of claim 1 exposure
Different hydrate or anhydrous form	Potentially lower risk, subject to conversion and equivalence evidence
Amorphous doripenem	Lower literal product-claim risk, with stability and manufacturability issues
Powder-filled injectable	High risk if the claimed crystal is present
Liquid product	Claim 2 or 3 may not apply after complete dissolution, but claim 5 and manufacturing facts matter
Alternative crystallization process	May avoid claim 4 while still infringing claim 1
Foreign manufacture	U.S. importation and supply activities remain relevant
Biosimilar pathway	Not applicable because doripenem is a small-molecule drug

The patent is a targeted barrier rather than a complete substitute for the foundational doripenem patent estate. A freedom-to-operate review must include composition, salt, formulation, process, impurity, sterile manufacturing, and regulatory patents across the United States, Europe, Japan, and other target markets.

What licensing and settlement issues affect this patent?

A license to a foundational doripenem patent would not necessarily grant rights under Patent 8,247,402. The patent is assigned to the Shionogi-related estate, and rights may have been transferred, licensed, or subject to commercial agreements connected with Doribax.

Relevant diligence points include:

Assignment records at the USPTO;
Patent-family ownership in Japan and Europe;
Any license covering doripenem crystalline forms;
Manufacturing rights for sterile injectable powder;
Supply agreements for doripenem API;
Paragraph IV settlement agreements; and
Any authorized-generic or delayed-entry arrangement.

No settlement terms should be inferred without a filed agreement, court order, or regulatory disclosure.

What is the geographic coverage of the doripenem crystal patent family?

U.S. Patent 8,247,402 provides enforceable rights in the United States. Corresponding foreign applications may protect the same crystal form or related processes, but foreign rights must be reviewed independently because:

Claim scope varies by jurisdiction;
Patent-term dates differ;
Some applications may have lapsed or been abandoned;
Opposition and invalidity proceedings may alter European coverage; and
Regulatory product listings differ by country.

The key geographic markets for a doripenem generic strategy are the United States, European Union, Japan, China, South Korea, Canada, and major hospital-antibiotic markets. U.S. patent expiration does not establish freedom to launch elsewhere.

Key Takeaways

U.S. Patent 8,247,402 is directed principally to a specific doripenem monohydrate crystal identified by PXRD.
Claim 1 is the core commercial claim and can reach the API, while claims 2 and 3 extend protection to solid medicaments and powder-filled preparations.
Claim 4 covers a defined aqueous crystallization, PXRD selection, and drying process.
Claim 5 covers preparation of an injectable solution from the claimed crystal or medicament.
The nominal patent expiration is December 28, 2027, subject to USPTO term adjustments or other recorded extensions.
The patent does not provide biosimilar exclusivity because doripenem is a small molecule regulated through the ANDA framework.
A generic manufacturer’s principal design-around option is a different, stable doripenem solid form that does not convert into the patented monohydrate.
The supplied text contains a material inconsistency between the PXRD peaks in claim 1 and the different peaks recited in claim 4.
Orange Book listing, Paragraph IV exposure, and litigation risk must be determined from the current FDA listing, USPTO record, and federal court docket rather than from the claim language alone.

FAQs About U.S. Patent 8,247,402 and Doripenem

Does Patent 8,247,402 cover all doripenem products?

No. It covers a specified doripenem monohydrate crystal and products containing that crystal. It does not, on the supplied claims, cover every doripenem salt, hydrate, polymorph, amorphous form, or formulation.

Can a generic company avoid the patent by using an anhydrous doripenem form?

Potentially. The alternative must be characterized through solid-state testing and evaluated for conversion to the patented monohydrate during manufacturing, storage, sterilization, reconstitution, and distribution.

Is Patent 8,247,402 a composition-of-matter patent?

No. It is primarily a crystal-form patent, with related medicament, process, and injectable-preparation claims.

Does a powder-filled vial necessarily infringe claim 3?

No. Infringement depends on whether the vial contains the claimed doripenem monohydrate crystal and satisfies the other limitations of claim 2 and claim 3.

Can a company manufacture the crystal outside the United States and sell it in the United States?

Foreign manufacture does not eliminate U.S. exposure. Importation, sale, offer for sale, and certain supply activities can create infringement risks under U.S. patent law, including process-patent provisions where applicable.

References

U.S. Patent and Trademark Office. (n.d.-a). U.S. Patent No. 8,247,402, Patent Center and Patent Assignment records. https://patentcenter.uspto.gov/
U.S. Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
U.S. Food and Drug Administration. (2014). Drug safety communication and product information for Doribax (doripenem). https://www.fda.gov/
U.S. Food and Drug Administration. (2007). Doribax prescribing information. NDA 021406. https://www.accessdata.fda.gov/
Hatch-Waxman Act, 21 U.S.C. § 355.
U.S. Patent and Trademark Office. (n.d.-b). Patent term adjustment and patent term extension guidance. https://www.uspto.gov/patents/laws/patent-term-calculator

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2000-99868	Mar 31, 2000

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1270575	⤷ Start Trial	333	Finland	⤷ Start Trial
Austria	304014	⤷ Start Trial
Australia	2001244692	⤷ Start Trial
Australia	4469201	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,247,402

Summary for Patent: 8,247,402