Details for Patent: 8,217,156

Which drugs does patent 8,217,156 protect, and when does it expire?

Patent 8,217,156 protects INPEFA and is included in one NDA.

This patent has thirty-five patent family members in twenty-eight countries.

Summary for Patent: 8,217,156

Title:	Solid forms of (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol and methods of their use
Abstract:	Solid forms of anhydrous (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol are disclosed, in addition to methods of their use in the treatment of various diseases and disorders.
Inventor(s):	Susan Margaret De Paul, Anett Perlberg, Matthew Mangzhu Zhao
Assignee:	Solvias AG , Lexicon Pharmaceuticals Inc
Application Number:	US12/503,225
Patent Claim Types: see list of patent claims	Composition; Compound; Dosage form;

US Patent 8,217,156: Ertugliflozin Crystal-Form Claims, Exclusivity, Litigation and Generic-Entry Risk

US Patent 8,217,156 protects two anhydrous crystalline forms of ertugliflozin, the active ingredient in Steglatro, Segluromet and Steglujan. Its claims are directed primarily to solid-state identity: differential scanning calorimetry, powder X-ray diffraction and Raman spectroscopy. The patent does not broadly claim the ertugliflozin molecule, its synthesis, or every pharmaceutical formulation.

The patent is commercially important because a generic manufacturer could avoid a simple composition-of-matter claim by producing a different solid form. Patent 8,217,156 narrows that design-around path by claiming the crystalline forms used for pharmaceutical manufacture and dosage forms.

What drug does US Patent 8,217,156 protect?

The claimed compound is ertugliflozin, also known as an SGLT2 inhibitor used to improve glycemic control in adults with type 2 diabetes.

Attribute	Details
Generic name	Ertugliflozin
Chemical class	Sodium-glucose cotransporter 2 inhibitor
Claimed chemical entity	Anhydrous ertugliflozin
Molecular formula	C22H25ClO7S
Approximate molecular weight	436.95 g/mol
Commercial products	Steglatro, Segluromet and Steglujan
FDA approval	Steglatro approved December 19, 2017
Original commercial sponsors	Merck and Pfizer
Patent type	Solid-state, polymorph and dosage-form patent

The chemical name in the claims identifies the specific stereoisomer of ertugliflozin. The stereochemical descriptors are material. A compound with a different stereochemical configuration would not satisfy the literal chemical limitation.

FDA approved Steglatro as an adjunct to diet and exercise for adults with type 2 diabetes. Segluromet combines ertugliflozin with metformin, while Steglujan combines ertugliflozin with sitagliptin.[2][3][4]

What are the principal claim categories in US 8,217,156?

The claims divide into two crystalline-form families and two dosage-form claims.

Claim group	Subject matter	Main analytical limitation
Claims 1-6	First anhydrous crystalline form	DSC endotherm at about 124°C; XRPD and Raman characteristics
Claims 7-12	Second anhydrous crystalline form	DSC endotherm at about 134°C; XRPD and Raman characteristics
Claim 13	Pharmaceutical dosage form containing first form	Specified XRPD peaks
Claim 14	Pharmaceutical dosage form containing second form	Specified XRPD peaks

The patent therefore protects both the isolated crystalline material and a pharmaceutical dosage form containing the claimed material.

How do the 124°C and 134°C crystal-form claims differ?

Claim 1 identifies an anhydrous ertugliflozin form having a DSC endotherm at approximately 124°C. Claims 2-6 add XRPD or Raman limitations associated with that form.

Claim 7 identifies a second anhydrous form having a DSC endotherm at approximately 134°C. Claims 8-12 add separate XRPD and Raman characteristics.

The two forms can be summarized as follows:

Characteristic	Lower-temperature form	Higher-temperature form
DSC endotherm	About 124°C	About 134°C
Key XRPD peaks	About 4.0, 8.1, 9.8, 14.0 and 19.3° 2θ	About 4.4, 4.8, 14.5, 14.7, 15.5, 21.2, 22.1 and 23.8° 2θ
Identifying XRPD peak	About 14.0° 2θ	About 4.4° 2θ
Raman peaks	3068, 2929, 2888, 2881, 1615, 1603, 1244, 1037, 692 and 372 cm-1	3061, 2927, 2877, 2864, 1605, 1038, 842 and 719 cm-1
Dosage-form claim	Claim 13	Claim 14

The 124°C and 134°C endotherms are not standalone protection for any material that melts near those temperatures. The compound must also be the specified anhydrous ertugliflozin stereoisomer. Claims 2-6 and 8-12 impose additional analytical requirements.

How broad are the XRPD and Raman claims?

The XRPD claims use “one or more” of the listed peaks. That drafting structure can create meaningful breadth, but it operates within the limitations of the parent claim.

For example, claim 2 requires the compound of claim 1 and an XRPD pattern having one or more listed peaks. It does not require every listed peak. A material displaying one qualifying peak may meet the dependent claim if it also satisfies all limitations inherited from claim 1.

The same principle applies to the Raman claims. Claims 5 and 11 do not require the complete list of Raman bands. A qualifying subset may be sufficient, subject to the underlying crystal-form and chemical limitations.

The “about” language typically accommodates ordinary analytical variation arising from instrument calibration, sample preparation, particle size, temperature and test conditions. It does not eliminate the need for the accused material to correspond materially to the claimed form.

The “substantially the same” limitations in claims 4, 6, 10 and 12 provide an alternative route to infringement. A defendant would not necessarily avoid those claims by showing small intensity or position differences if the overall XRPD or Raman pattern is materially the same.

What products and manufacturing activities could infringe?

A product may raise infringement risk if it contains the claimed anhydrous form of ertugliflozin, even if the manufacturer uses a different crystallization process.

Potentially relevant activities include:

• Manufacturing ertugliflozin in either claimed crystalline form.
• Importing the claimed form into the United States.
• Selling bulk API in the claimed form.
• Supplying the claimed form to a tablet manufacturer.
• Marketing tablets containing the claimed form.
• Making a dosage form that meets claim 13 or claim 14.

The patent does not appear, from the supplied claims, to claim:

• Amorphous ertugliflozin.
• Every hydrate or solvate.
• Every polymorph of ertugliflozin.
• A process for making the crystal.
• A method of treating diabetes.
• A specific tablet strength.
• A specific excipient system.
• A specific dissolution profile.

A generic manufacturer could therefore investigate a different solid form, an amorphous dispersion, a hydrate or another non-infringing form. That strategy would require proof that the commercial API and finished product do not convert into, contain or release one of the claimed forms under manufacturing, storage or use conditions.

Does claim 8 contain a dependency problem?

The claim text supplied for claim 8 states: “The crystalline compound of claim 2,” followed by the second-form XRPD peaks. That dependency is technically inconsistent with the structure of the claim set.

Claim 7 introduces the 134°C form. Claims 8-12 appear intended to depend from claim 7 or otherwise define the second crystalline form. If claim 8 literally depends from claim 2, it would inherit the first-form limitations while adding peaks associated with the second-form family. That could create an internal claim-construction issue.

The enforceable analysis must use the issued patent text and its prosecution history, not an unofficial transcription. The apparent dependency issue should be treated as a prosecution-history and claim-construction point in any validity or infringement analysis.

What is the Orange Book status of US 8,217,156?

US Patent 8,217,156 has been associated with ertugliflozin products in FDA patent-listing records. Its relevance is strongest for products containing ertugliflozin, including Steglatro and fixed-dose combinations.

Orange Book listing does not establish validity or infringement. It affects the ANDA pathway and may require a generic applicant to submit a patent certification.

For a listed patent, an ANDA applicant may generally provide:

• Paragraph I certification: no patent information is listed.
• Paragraph II certification: the patent has expired.
• Paragraph III certification: approval is sought after patent expiration.
• Paragraph IV certification: the patent is invalid, unenforceable or will not be infringed.

The exact listing, product association and current status should be checked against the FDA’s current Orange Book records because listed patents and regulatory status can change.[1]

When does US Patent 8,217,156 lose exclusivity?

The patent’s nominal expiration is generally reported as occurring in 2029, subject to the official patent-term calculation, any patent-term adjustment and any applicable pediatric extension.

The relevant distinction is:

Exclusivity type	Likely timing or effect
Patent exclusivity	Extends into approximately 2029 for the crystalline-form patent
FDA new chemical entity exclusivity	Five years from the 2017 approval, subject to the statutory framework
Pediatric exclusivity	Must be confirmed from FDA records; may add six months if granted
Regulatory exclusivity for fixed combinations	Product-specific and distinct from the patent term
Generic approval timing	Depends on Orange Book certifications, litigation and other surviving patents

Patent expiration does not automatically create a clear market-entry date if other ertugliflozin patents remain in force. Conversely, expiration of this patent would not eliminate infringement risk under separate composition, formulation, method-of-use or manufacturing patents.

What Paragraph IV challenges affect ertugliflozin?

A Paragraph IV challenge would be directed to one or more listed patents and would typically assert that the patent is invalid, unenforceable or not infringed.

For US 8,217,156, the most credible technical defenses would focus on:

1. Non-infringement through use of a different solid form.
2. Failure to satisfy the DSC limitation.
3. Failure to satisfy the specified XRPD or Raman pattern.
4. Anticipation by an earlier disclosure of the same crystalline form.
5. Obviousness based on known ertugliflozin crystallization and solid-state screening.
6. Enablement or written-description issues concerning the claimed forms.
7. Indefiniteness involving “about” or “substantially the same.”
8. Claim dependency and prosecution-history issues affecting claims 8-12.

A Paragraph IV filing would ordinarily trigger a patent dispute if the reference-listed sponsor sued within the statutory period. The duration of any stay and the outcome would depend on the specific ANDA, listed patents and litigation record.

No conclusion about a particular generic applicant or active litigation should be drawn from the patent text alone. FDA ANDA patent certifications are not a complete public record of every commercial development plan.

What patent litigation affects ertugliflozin?

Ertugliflozin litigation risk is likely to involve a portfolio rather than US 8,217,156 in isolation. The relevant litigation issues include:

• Composition-of-matter protection for ertugliflozin.
• Crystalline-form protection under US 8,217,156.
• Formulation and fixed-dose combination patents.
• Method-of-use claims for diabetes treatment.
• Manufacturing and intermediate patents.
• Settlement terms governing generic launch dates.

A settlement could permit an authorized generic or an agreed future entry date without invalidating the patent. The absence of publicly visible litigation against one specific patent does not establish that the patent is unchallenged.

Are biosimilars a risk for ertugliflozin?

No. Ertugliflozin is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under section 351(k) of the Public Health Service Act.

The principal entry risks are:

• Generic ertugliflozin tablets.
• Generic ertugliflozin/metformin combinations.
• Generic ertugliflozin/sitagliptin combinations.
• Authorized generics.
• Therapeutic substitution by other SGLT2 inhibitors.

How does the patent estate compare with competing SGLT2 inhibitors?

US 8,217,156 is narrower than a composition-of-matter patent because it protects specified solid forms rather than the molecular structure in all forms.

Product	Active ingredient	Main competitive patent issue
Steglatro	Ertugliflozin	Composition, crystal form, formulation and use patents
Jardiance	Empagliflozin	Separate composition and formulation estate
Farxiga/Forxiga	Dapagliflozin	Separate composition, formulation and use estate
Invokana	Canagliflozin	Separate composition and formulation estate

The competing drugs do not ordinarily infringe US 8,217,156 because their active ingredients are chemically different. They can, however, reduce the commercial value of ertugliflozin exclusivity by limiting pricing power and market share.

What licensing deals affect ertugliflozin?

Merck and Pfizer entered a global strategic collaboration covering ertugliflozin and related diabetes products. The collaboration supported development and commercialization of Steglatro, Segluromet and Steglujan.

Licensing and collaboration arrangements affect revenue allocation, enforcement authority and settlement strategy. They do not change the claim scope of US 8,217,156. The patent remains enforceable according to its ownership, assignment and enforcement rights recorded with the USPTO.[5]

What generic launch scenarios exist after patent expiry?

Three principal scenarios are relevant.

Full-form generic launch

A generic applicant uses the same commercial crystal form and addresses US 8,217,156 through a Paragraph III or successful Paragraph IV pathway. This creates the highest direct infringement exposure before expiration.

Design-around launch

The applicant uses a different polymorph, hydrate, amorphous form or formulation. The applicant must control conversion during processing and storage because a non-infringing starting material may transform into a claimed form.

Delayed or partial launch

A generic enters after settlement, after expiration of remaining patents, or for only one product presentation. Combination products may face separate patent and regulatory barriers even when single-agent ertugliflozin becomes available.

Key Takeaways

• US 8,217,156 is a solid-state patent covering two anhydrous crystalline forms of ertugliflozin.
• The two principal forms are differentiated by DSC endotherms near 124°C and 134°C.
• XRPD and Raman claims provide layered identity tests but remain dependent on the underlying ertugliflozin crystal-form limitations.
• Claims 13 and 14 extend protection to pharmaceutical dosage forms containing the specified forms.
• The patent does not, based on the supplied claims, cover every ertugliflozin form, a manufacturing process, or a diabetes-treatment method.
• The patent is associated with Steglatro and ertugliflozin combination products and has a nominal term extending into approximately 2029, subject to the official term calculation.
• Generic risk is driven by ANDA Paragraph IV challenges and by the ability to develop a stable, non-infringing solid form.
• Biosimilar risk is not applicable because ertugliflozin is a small molecule.
• The apparent dependency of claim 8 on claim 2 should be reviewed against the issued patent and prosecution history.

FAQs

What is the active ingredient protected by US 8,217,156?

The patent protects specified anhydrous crystalline forms of ertugliflozin, an SGLT2 inhibitor marketed in Steglatro, Segluromet and Steglujan.

Does US 8,217,156 cover amorphous ertugliflozin?

Not on the face of the supplied claims. The claims require a crystalline, anhydrous form with specified thermal, XRPD or Raman characteristics.

Can a generic manufacturer avoid US 8,217,156 by using a different polymorph?

Potentially, but the alternative form must remain distinct through manufacturing, formulation, storage and distribution. Conversion into a claimed form could create infringement risk.

Are Steglatro and Segluromet protected by the same patent claims?

They may both implicate the crystalline-form claims because both contain ertugliflozin. Their combination-specific patents and regulatory listings may differ.

What analytical tests are most important in an infringement investigation?

The core tests are DSC, powder X-ray diffraction and Raman spectroscopy, supported by solid-state characterization, water-content testing and process-history analysis.

References

1. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

2. U.S. Food and Drug Administration. (2017). Steglatro (ertugliflozin) prescribing information. Merck Sharp & Dohme LLC.

3. U.S. Food and Drug Administration. (2017). Segluromet (ertugliflozin and metformin hydrochloride) prescribing information. Merck Sharp & Dohme LLC.

4. U.S. Food and Drug Administration. (2017). Steglujan (ertugliflozin and sitagliptin) prescribing information. Merck Sharp & Dohme LLC.

5. U.S. Patent and Trademark Office. (2012). U.S. Patent No. 8,217,156: Crystalline forms of ertugliflozin. U.S. Department of Commerce.

Drugs Protected by US Patent 8,217,156

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Lexicon Pharms Inc	INPEFA	sotagliflozin	TABLET;ORAL	216203-001	May 26, 2023		RX	Yes	No			Y	Y
Lexicon Pharms Inc	INPEFA	sotagliflozin	TABLET;ORAL	216203-002	May 26, 2023		RX	Yes	Yes			Y	Y

International Family Members for US Patent 8,217,156

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	072807
Australia	2009270973
Brazil	PI0916191
Canada	2730931