US Patent 8,513,202: Canagliflozin Hemihydrate Claims, Scope and Patent Landscape
US Patent 8,513,202 protects a specific crystalline hemihydrate form of canagliflozin, the active ingredient in Invokana. The patent does not broadly claim every form of canagliflozin. Its central limitation is a crystalline canagliflozin hemihydrate identified by four principal infrared absorption peaks at 1626, 1600, 1549, and 1507 cm⁻¹. The patent also covers processes, pharmaceutical compositions, therapeutic uses, and SGLT inhibition methods involving that form. (U.S. Patent No. 8,513,202, 2013)
The patent is important because solid-state form claims can block commercial generic manufacture even after an earlier compound patent expires, provided the generic product uses the claimed crystalline form.
What drug does US Patent 8,513,202 protect?
The claimed compound is canagliflozin, chemically identified as 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene. The patent claims a hemihydrate crystalline form of canagliflozin.
Canagliflozin is an orally administered sodium-glucose cotransporter 2, or SGLT2, inhibitor. It is marketed by Janssen under the brand name Invokana. Canagliflozin increases urinary glucose excretion by reducing renal glucose reabsorption. The FDA approved Invokana in 2013 for glycemic control in adults with type 2 diabetes, subject to subsequent label changes and cardiovascular and renal indications. (FDA, 2024)
| Item |
Information |
| Active ingredient |
Canagliflozin |
| Drug class |
SGLT2 inhibitor |
| Brand |
Invokana |
| Patent subject |
Crystalline canagliflozin hemihydrate |
| Patent number |
US 8,513,202 |
| Patent type |
Solid-state form, process, composition, and method-of-use claims |
| Patent grant date |
August 20, 2013 |
| Primary commercial relevance |
Generic substitution and manufacturing-form control |
| FDA pathway |
New Drug Application and Abbreviated New Drug Application framework |
What is the core claim of US Patent 8,513,202?
Claim 1 is the commercial center of the patent. It claims a crystalline canagliflozin hemihydrate having a specified infrared spectrum in mineral oil with main peaks at:
- 1626 cm⁻¹
- 1600 cm⁻¹
- 1549 cm⁻¹
- 1507 cm⁻¹
The claim combines three technical concepts:
- The chemical identity of canagliflozin.
- The presence of approximately one-half molecule of water per canagliflozin molecule.
- A crystalline solid state characterized by infrared peaks.
The claim is narrower than a claim to canagliflozin itself. It does not expressly cover every anhydrous, amorphous, solvated, hydrated, or polymorphic form of the active ingredient.
How does the infrared limitation affect infringement?
The infrared limitation provides an analytical fingerprint. A product is more likely to fall within claim 1 if:
- It is chemically canagliflozin.
- It is a crystalline hemihydrate.
- Its infrared spectrum shows the listed principal peaks under materially comparable testing conditions.
The listed peaks are not necessarily the only required spectral characteristics. The claim states that the form has an infrared spectrum "comprising" the specified main peaks. "Comprising" generally permits additional spectral peaks, but the claimed form must still satisfy the overall crystalline-form limitation.
In a patent dispute, the parties would likely contest:
- Whether the accused material is a true hemihydrate.
- Whether water content is stoichiometric, variable, or merely adsorbed.
- Whether the infrared peaks match the claimed form.
- Whether sample preparation in mineral oil affects peak position.
- Whether differences in polymorphic conversion occur during formulation or storage.
- Whether the generic manufacturer uses the same solid form at the drug-substance or finished-product stage.
Powder X-ray diffraction, thermogravimetric analysis, Karl Fischer water analysis, differential scanning calorimetry, and infrared spectroscopy would be expected analytical tools. The claim itself, however, expressly identifies infrared peaks rather than relying solely on an X-ray diffraction pattern.
How many patent claims does US 8,513,202 contain?
The supplied claims contain five independent claim categories, although claim 2 expressly depends on claim 1.
| Claim |
Claim category |
Protected subject |
| 1 |
Product claim |
Crystalline canagliflozin hemihydrate identified by IR peaks |
| 2 |
Process claim |
Preparing the claimed form by solution precipitation or recrystallization |
| 3 |
Composition claim |
Pharmaceutical composition containing the claimed form |
| 4 |
Therapeutic-use claim |
Treating or delaying diabetes and associated disorders |
| 5 |
Biological-use claim |
Inhibiting a sodium-dependent glucose transporter |
Claim 1 is the strongest blocking claim for a generic that uses the patented solid form. Claims 3 through 5 extend protection to commercial use, while claim 2 targets manufacture.
What formulations are protected by US Patent 8,513,202?
Claim 3 covers a pharmaceutical composition comprising an effective amount of the claimed crystalline hemihydrate and a pharmaceutically acceptable carrier.
The claim is broad as to the carrier. It can potentially reach tablets, capsules, granules, powders, or other oral dosage forms containing the claimed crystalline form. The claim does not require a particular excipient, dosage strength, release profile, or manufacturing method.
Potentially relevant dosage-form elements include:
- Immediate-release tablets.
- Oral solid formulations containing canagliflozin hemihydrate.
- Formulations with binders, diluents, lubricants, disintegrants, and coatings.
- Combination products if they contain the claimed canagliflozin form.
- Finished dosage forms in which the crystalline form remains identifiable.
The composition claim may be less useful against a generic that changes the active solid form, but it can provide a second infringement theory when the generic uses the patented hemihydrate in its tablets.
The claim does not expressly require:
- A particular canagliflozin dose.
- A particular excipient.
- A particular tablet coating.
- A fixed-dose combination with metformin or another drug.
- A specific dissolution profile.
- A particular release mechanism.
What process does claim 2 protect?
Claim 2 covers preparing the claimed crystalline hemihydrate by:
- Forming a solution of canagliflozin.
- Crystallizing the hemihydrate from that solution by precipitation or recrystallization.
The process claim is directed to solution-mediated formation of the solid form. It does not appear limited to a particular solvent, temperature, concentration, seeding protocol, cooling rate, or agitation condition in the supplied claim text.
This creates potential manufacturing risk for a generic that uses:
- Dissolution followed by controlled precipitation.
- Recrystallization from a solvent system.
- Seeding with the patented hemihydrate.
- Solvent exchange that produces the hemihydrate.
- A recovery process that converts another form into the hemihydrate.
The claim may be avoided if the generic uses a different solid form or a process that does not form the claimed hemihydrate from solution. That conclusion would depend on the actual manufacturing process and the final drug substance.
What medical uses are protected by claims 4 and 5?
Claim 4 covers administering the claimed crystalline hemihydrate for a wide group of metabolic and vascular conditions. The listed conditions include:
- Diabetes mellitus.
- Hyperglycemia.
- Insulin resistance.
- Hyperinsulinemia.
- Obesity.
- Hyperlipidemia.
- Hypertriglyceridemia.
- Diabetic retinopathy.
- Diabetic neuropathy.
- Diabetic nephropathy.
- Delayed wound healing.
- Atherosclerosis.
- Hypertension.
- Syndrome X.
- Elevated fatty acids.
- Elevated glycerol.
- Diabetic complications.
Claim 5 covers administration to inhibit a sodium-dependent glucose transporter in a mammal.
These claims are method claims. They require administration of the specific crystalline hemihydrate, not merely administration of any canagliflozin product. A generic product using the patented form could face method-of-use exposure if its labeling directs or encourages use for a covered indication.
The practical strength of claim 4 depends on the relationship between the patented method language and the FDA-approved label. Under the Hatch-Waxman framework, a generic applicant may use a section viii statement to carve out patented indications when the labeling supports a lawful carve-out. A carve-out does not necessarily eliminate all risk if the remaining label or product instructions still encourage the patented use.
When does US Patent 8,513,202 lose exclusivity?
The statutory patent term is generally 20 years from the applicable nonprovisional or international filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments. Public patent records associate the patent with a 2029 expiration timeframe. The operative date for commercial planning is the expiration date shown in the current USPTO and FDA records, including any applicable adjustment. (USPTO, 2024; FDA, 2024)
| Exclusivity layer |
Relevance to Invokana |
| Canagliflozin compound patents |
Protect the active molecule and may expire earlier |
| US 8,513,202 |
Protects the crystalline hemihydrate form |
| Method-of-use patents |
May cover diabetes, renal, cardiovascular, or other indications |
| FDA regulatory exclusivity |
Separate from patent term and generally shorter |
| Pediatric exclusivity |
Can extend listed patents by six months if granted |
| Formulation or combination patents |
May cover Invokamet or other products separately |
Patent expiry does not automatically establish an immediate generic launch date. FDA approval timing, paragraph IV litigation, settlement restrictions, manufacturing readiness, and the scope of any other unexpired patents remain relevant.
What is the Orange Book status of US 8,513,202?
US Patent 8,513,202 has been associated with Invokana’s patent protection and is relevant to Orange Book-based generic certification analysis. The Orange Book listing determines whether an ANDA applicant must make a paragraph I, II, III, or IV certification against the patent.
For a listed drug patent directed to the active ingredient or an approved use, an ANDA applicant may need to certify that:
- The patent information is inaccurate or invalid.
- The patent will not be infringed.
- The applicant will wait until patent expiry.
- The applicant will challenge the patent through a paragraph IV certification.
The exact current listing, use code, delisting history, pediatric extension, and expiration date should be verified against the latest FDA Orange Book data and the patent’s current USPTO record. The claim text alone does not establish the current regulatory listing status.
Which companies are challenging the Invokana patent estate?
The supplied record does not identify specific ANDA applicants, paragraph IV notices, district court actions, or settlement agreements. Those facts cannot be derived from the five claims.
For competitive intelligence, relevant litigation questions include:
- Whether an ANDA applicant certified paragraph IV against US 8,513,202.
- Whether Janssen filed a Hatch-Waxman action within 45 days.
- Whether the case was stayed for up to 30 months.
- Whether the parties entered a launch-date settlement.
- Whether the generic applicant agreed to an authorized-generic arrangement.
- Whether the litigation involved the crystalline-form claims, compound claims, or method-of-use claims.
- Whether the court construed "hemihydrate," "crystalline form," or the infrared limitations.
A paragraph IV challenge would likely attack validity under anticipation, obviousness, written description, enablement, indefiniteness, or lack of crystalline-form distinction. It could also assert noninfringement based on a different polymorph, amorphous form, hydrate state, or manufacturing route.
How strong is the patent estate for canagliflozin?
The estate is strongest where a generic uses the same commercial drug substance form. Claim 1 provides a product-based infringement theory, which is generally more direct than a process claim. Claim 3 adds finished-product exposure, while claims 4 and 5 create use-based theories.
| Risk area |
Relative exposure |
| Generic uses claimed crystalline hemihydrate |
High |
| Generic uses a different crystalline polymorph |
Fact-dependent |
| Generic uses amorphous canagliflozin |
Lower under claim 1 |
| Generic uses anhydrous canagliflozin |
Lower under claim 1 |
| Generic process uses solution recrystallization |
Potentially high |
| Generic label includes covered treatment |
Method-of-use risk |
| Generic carves out patented indication |
Risk may be reduced |
| Generic uses a different active ingredient form |
Requires separate technical analysis |
The principal vulnerability is narrowness. The patent does not claim the entire canagliflozin molecule. A technically and commercially viable alternative solid form could avoid claim 1 if it does not meet the hemihydrate and infrared requirements. That design-around strategy may create new risks involving bioequivalence, stability, dissolution, scale-up, and other patents.
What geographic coverage does US 8,513,202 provide?
The patent provides rights only in the United States. Corresponding international and foreign applications may protect the same crystalline form in Europe, Japan, Canada, Australia, and other jurisdictions, but foreign claims, prosecution history, expiration dates, and litigation outcomes must be analyzed separately.
US protection can block:
- Manufacturing in the United States.
- Importation of infringing canagliflozin drug substance.
- Importation of finished tablets containing the claimed form.
- Commercial sale, use, or offer for sale in the United States.
- Certain acts of foreign manufacture that trigger US importation liability.
The patent does not itself establish protection in countries where no corresponding patent remains in force.
What generic launch scenarios exist for Invokana?
The main launch pathways are:
- Wait for patent expiry. The generic applicant avoids litigation risk but delays entry.
- Paragraph IV challenge. The applicant seeks earlier approval and challenges validity or infringement.
- Design around the crystalline form. The applicant uses an alternative canagliflozin solid form.
- Section viii labeling carve-out. The applicant removes patented indications where FDA labeling permits.
- Settlement or licensed entry. The applicant obtains a negotiated launch date or other commercial rights.
- Authorized generic competition. The brand holder or licensee supplies a generic-equivalent product under separate commercial terms.
A design-around is most credible when the alternative form has a distinct water content, crystal structure, thermal profile, and infrared or X-ray signature. It must also satisfy FDA quality, stability, dissolution, and bioequivalence requirements.
Key Takeaways
- US 8,513,202 is a solid-state patent directed to crystalline canagliflozin hemihydrate.
- Claim 1 is limited by the chemical identity, hemihydrate state, crystalline form, and specified infrared peaks.
- Claims 2 through 5 extend protection to manufacture, pharmaceutical compositions, treatment methods, and SGLT inhibition.
- The patent does not broadly cover all canagliflozin forms.
- A generic using the same hemihydrate faces the clearest infringement risk.
- Anhydrous, amorphous, or different polymorphic forms may offer design-around paths, subject to technical and regulatory constraints.
- The patent is associated with Invokana’s US patent estate and has a 2029-era statutory expiration timeframe, subject to the operative USPTO and FDA records.
- Paragraph IV exposure depends on the applicant’s actual drug substance, manufacturing process, ANDA labeling, and certification strategy.
- The claims supplied do not establish specific challengers, settlements, litigation outcomes, or current Orange Book use codes.
FAQs
Does US 8,513,202 cover all canagliflozin products?
No. The claims focus on a specific crystalline hemihydrate form. Products using a different polymorph, anhydrous form, or amorphous form require separate infringement analysis.
Can a generic avoid US 8,513,202 by using anhydrous canagliflozin?
Potentially. An anhydrous product may avoid claim 1 if it does not contain the claimed hemihydrate and does not exhibit the claimed crystalline-form characteristics. Process, formulation, and other canagliflozin patents may still apply.
Is the infrared spectrum alone enough to establish infringement?
Not necessarily. The claim requires the claimed canagliflozin crystalline hemihydrate with the listed infrared peaks. Infrared analysis would normally be evaluated with water-content, thermal, crystallographic, and chemical identity data.
Does claim 4 cover every use of Invokana for diabetes?
Claim 4 covers the listed therapeutic uses involving the claimed crystalline hemihydrate. The enforceability and practical reach of the claim depend on claim construction, the approved label, induced-use evidence, and any FDA-approved labeling carve-out.
Does patent expiration guarantee immediate generic entry?
No. Generic entry also depends on FDA approval, other unexpired patents, litigation or settlement terms, manufacturing readiness, regulatory exclusivity, and the commercial viability of the proposed product.
References
Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024). Invokana (canagliflozin) prescribing information. Janssen Pharmaceuticals, Inc.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term information. U.S. Department of Commerce.
U.S. Patent No. 8,513,202. (2013). Crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate. United States Patent and Trademark Office.
