United States Patent 10,307,419: Brexpiprazole Tablet Claims, Patent Scope, and Generic-Entry Landscape
U.S. Patent No. 10,307,419 protects a narrowly defined tablet formulation and manufacturing process for brexpiprazole, the active ingredient in Rexulti. The patent does not broadly claim brexpiprazole as a molecule. Its enforceable scope depends on the combined presence of specified excipients, hydroxypropyl cellulose binder, selected disintegrants, magnesium stearate, an HPMC/talc coating containing iron oxide and titanium oxide, and a coating that substantially lacks polyethylene glycol.
The patent was issued June 4, 2019, to Otsuka Pharmaceutical Co., Ltd. Its commercial relevance is primarily formulation protection for Rexulti tablets and potential barriers to generic products that copy the listed inactive-ingredient architecture or manufacturing process.
What drug does U.S. Patent 10,307,419 protect?
The claimed active ingredient is 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, commonly known as brexpiprazole.
| Item |
Information |
| Active ingredient |
Brexpiprazole |
| Brand |
Rexulti |
| Sponsor |
Otsuka Pharmaceutical Co., Ltd. |
| Drug class |
Atypical antipsychotic |
| Dosage form |
Film-coated tablet |
| FDA approval |
Schizophrenia and adjunctive treatment of major depressive disorder |
| Patent at issue |
U.S. 10,307,419 |
| Patent type |
Formulation and manufacturing-process patent |
| Issue date |
June 4, 2019 |
| Core protection |
Brexpiprazole tablet composition and wet-granulation/coating process |
Brexpiprazole was approved by the FDA in 2015. The patent at issue is not the principal compound patent. It protects a dosage-form configuration intended to provide acceptable tablet manufacture, disintegration, stability, and coating performance.
What patents protect Rexulti and brexpiprazole?
Rexulti’s broader intellectual-property position can be divided into four categories:
- Compound patents covering brexpiprazole or closely related quinolinone derivatives.
- Method-of-use patents covering schizophrenia and major depressive disorder treatment.
- Formulation patents covering tablets and inactive ingredients.
- Manufacturing-process patents covering granulation, compression, and film coating.
U.S. Patent 10,307,419 falls into the third and fourth categories. It does not, based on the supplied claims, cover every pharmaceutical composition containing brexpiprazole.
Patent landscape by protection type
| Protection category |
Relevance to Rexulti |
Scope of Patent 10,307,419 |
| Chemical compound |
Prevents commercial use of the active molecule |
Not the principal subject |
| Salt or solid form |
Can protect specific crystalline or salt forms |
Included only insofar as the tablet uses the active ingredient or a salt |
| Tablet formulation |
Protects inactive-ingredient combinations and ranges |
Central subject |
| Film coating |
Protects HPMC, talc, pigments, and PEG exclusion |
Central subject |
| Manufacturing method |
Protects wet granulation, lubrication, compression, and coating |
Claims 6 and 7 |
| Method of treatment |
Protects administration for a disease |
Not claimed |
| Device or delivery system |
Usually relevant to injectables or controlled release |
Not relevant |
The patent is therefore an incremental formulation patent. Its value is strongest against a generic that uses the same formulation design, not against every brexpiprazole product.
What does claim 1 cover?
Claim 1 is an independent composition claim directed to a coated tablet. It requires all of the following elements:
- Brexpiprazole or a salt thereof as the active ingredient.
- An excipient selected from lactose, corn starch, microcrystalline cellulose, or combinations of those materials.
- Hydroxypropyl cellulose as the binder.
- A disintegrant selected from:
- low-substituted hydroxypropyl cellulose;
- croscarmellose sodium; or
- sodium carboxymethyl starch.
- Magnesium stearate as the lubricant.
- The specified quantitative ranges in the uncoated tablet.
- A coating containing hydroxypropyl methylcellulose and talc.
- Iron oxide and titanium oxide as colorants.
- Colorant representing 0.1% to 50% by weight of the coating.
- Substantial absence of polyethylene glycol from the coating.
Claim 1 composition ranges
| Component |
Claimed range in the uncoated tablet |
| Brexpiprazole or salt |
0.05% to 25% by weight |
| Excipient |
10% to 98.5% |
| Hydroxypropyl cellulose |
0.1% to 20% |
| Disintegrant |
1% to 25% |
| Magnesium stearate |
0.1% to 10% |
The claim is cumulative. A tablet that contains brexpiprazole but omits hydroxypropyl cellulose, substitutes another lubricant for magnesium stearate, or uses a coating without the specified pigments would not literally satisfy claim 1.
The phrase “substantially does not contain polyethylene glycol” is particularly important. It creates a negative limitation directed to the coating. A coating with no polyethylene glycol is the clearest literal case. A formulation containing a trace amount may raise an infringement issue depending on the technical meaning established by the patent specification, prosecution history, and evidence of how the limitation was understood by a person skilled in the art.
How do claims 2 through 5 narrow the tablet protection?
Claims 2 through 5 are dependent claims. They add narrower compositional or process limitations.
| Claim |
Added limitation |
Commercial effect |
| 2 |
Specific component-to-active-ingredient weight ratios |
Narrows the formulation to ratio-defined embodiments |
| 3 |
Tablet is made from a wet-granulated substance |
Links protection to a wet-granulation manufacturing route |
| 4 |
No povidone or crospovidone |
Excludes two common binder or disintegrant alternatives |
| 5 |
Excipient contains lactose, corn starch, and microcrystalline cellulose; disintegrant is low-substituted hydroxypropyl cellulose |
Defines a highly specific formulation |
| 6 |
Manufacturing method with granulation, lubricant addition, compression, and coating |
Protects the production sequence |
| 7 |
Method claim limited to the claim 5 excipient/disintegrant combination |
Narrowest manufacturing embodiment |
Claim 4 is strategically relevant because it excludes povidone and crospovidone. A generic manufacturer using either material may avoid that dependent claim, although it could still infringe claim 1 if the product otherwise meets the broader limitations.
Claim 5 is narrower than claim 1 because it requires all three listed excipients: lactose, corn starch, and microcrystalline cellulose. A formulation using only microcrystalline cellulose, for example, could fall outside claim 5 while remaining within claim 1.
What manufacturing process does U.S. Patent 10,307,419 protect?
Claims 6 and 7 require a defined sequence:
- Granulate a mixture containing brexpiprazole, excipient, hydroxypropyl cellulose, and disintegrant.
- Add magnesium stearate to the granulated material.
- Compress the mixture into tablets.
- Prepare a coating mixture containing HPMC, talc, colorant, and liquid medium.
- Coat the tablet surface.
- Use iron oxide and titanium oxide as the colorants.
- Substantially exclude polyethylene glycol from the coating mixture.
The process claims are narrower than a general claim to manufacturing a brexpiprazole tablet. They are directed to the specified order of operations and formulation ingredients.
Wet granulation as a patent boundary
A generic manufacturer could potentially reduce infringement exposure by using:
- direct compression;
- dry granulation;
- a different binder;
- a different lubricant;
- a coating system containing polyethylene glycol;
- pigments other than iron oxide and titanium oxide;
- an uncoated or differently coated dosage form.
The legal result would depend on whether the final product infringes the composition claims independently of the process claims. A non-infringing process does not avoid liability if the resulting tablet falls within an asserted composition claim.
How strong is the patent estate for this formulation?
The patent has moderate formulation strength and limited molecule-level breadth.
Strengths
- It combines numerous formulation limitations, making the claim technically specific.
- It covers both the finished tablet and the manufacturing process.
- The negative PEG limitation may distinguish the claimed coating from conventional film-coating systems.
- Claim 1 does not require the narrower three-excipient combination in claim 5.
- The active ingredient concentration range is broad, spanning low-dose and higher-dose tablets.
Weaknesses
- The claim requires a particular combination of common pharmaceutical excipients.
- Generic manufacturers can often design around individual excipient limitations.
- The patent does not appear, from the supplied claims, to cover brexpiprazole itself.
- The coating limitations may be avoided through a different color system or coating polymer.
- The process claims may be difficult to enforce against a manufacturer where production evidence is unavailable.
- A formulation patent is generally less effective than a valid compound patent against a product using the same active ingredient but a different tablet design.
What formulations are most exposed to infringement?
A generic tablet has the highest literal-infringement exposure if it uses the following architecture:
| Feature |
High-risk configuration |
| Active |
Brexpiprazole or a salt |
| Main excipients |
Lactose, corn starch, and microcrystalline cellulose |
| Binder |
Hydroxypropyl cellulose |
| Disintegrant |
Low-substituted hydroxypropyl cellulose |
| Lubricant |
Magnesium stearate |
| Process |
Wet granulation followed by compression |
| Coating polymer |
Hydroxypropyl methylcellulose |
| Coating additive |
Talc |
| Pigments |
Iron oxide and titanium oxide |
| PEG |
Absent or present only below the legally meaningful threshold |
A generic using a different binder, such as povidone, could avoid the express hydroxypropyl-cellulose limitation. A generic using sodium stearyl fumarate instead of magnesium stearate could avoid another required limitation. These substitutions may affect tablet hardness, dissolution, manufacturability, and regulatory comparability.
When does U.S. Patent 10,307,419 expire?
The patent’s enforceable term depends on its earliest effective nonprovisional priority date, applicable patent-term adjustment, and any patent-term extension. The nominal term for a U.S. utility patent generally runs 20 years from the earliest effective nonprovisional filing date under 35 U.S.C. §154.
Public patent records identify the patent as issued June 4, 2019. The expiration date should be taken from the USPTO Patent Center record and the Orange Book listing rather than calculated from the issue date. Patent-term adjustment can move the expiration date beyond the basic 20-year term, while terminal disclaimers can shorten it. A formulation patent of this type would ordinarily have protection extending into the mid-2030s if its priority chain began in the mid-2010s.
The patent term should be analyzed separately from FDA regulatory exclusivity. FDA approval exclusivity for brexpiprazole does not control the expiration of Patent 10,307,419.
What is the Orange Book status of Patent 10,307,419?
Patent 10,307,419 is relevant to Rexulti’s Orange Book patent landscape because it claims a tablet dosage form containing brexpiprazole. Orange Book relevance depends on whether Otsuka submitted the patent for listing against a specific Rexulti strength and whether FDA accepted the listing.
An Orange Book listing can require an ANDA applicant to make a certification under section viii or one of the Paragraph I-IV categories. A formulation patent generally presents the following possibilities:
| ANDA strategy |
Effect |
| Paragraph III certification |
Applicant accepts delayed approval until patent expiration |
| Paragraph IV certification |
Applicant alleges the patent is invalid, unenforceable, or not infringed |
| Section viii statement |
Applicant omits a patented method of use, where legally available |
| Non-infringing formulation |
Applicant argues the listed formulation patent does not cover its product |
A tablet formulation patent ordinarily cannot be carved out through a section viii statement merely because the applicant omits a method of use. The applicant must address the formulation patent if it is listed against the dosage form and relevant to the proposed product.
Which companies are challenging Rexulti patents?
The supplied claim text does not establish that a particular company filed a Paragraph IV certification, received a 30-month stay, or became a defendant in litigation concerning Patent 10,307,419. Those facts must be tied to FDA Orange Book records, ANDA notices, and federal court dockets.
The important legal trigger is a Paragraph IV notice. If Otsuka files a patent-infringement action within 45 days after receiving notice, FDA approval of the ANDA may be stayed for up to 30 months, subject to statutory exceptions and court developments under the Hatch-Waxman Act. The patent’s listing status, not the patent text alone, determines whether this framework applies to an ANDA.
What patent litigation affects brexpiprazole generic entry?
The main litigation questions are:
- Whether Patent 10,307,419 is listed for the relevant Rexulti strength.
- Whether an ANDA applicant certifies Paragraph IV.
- Whether Otsuka sues within the statutory 45-day period.
- Whether the asserted claims survive claim construction and validity challenges.
- Whether the generic’s proposed inactive ingredients and coating fall within claim 1.
- Whether the generic’s manufacturing process can be proven to practice claims 6 or 7.
- Whether other Rexulti patents create separate approval or launch barriers.
A formulation-patent case would likely focus on claim construction for “substantially does not contain polyethylene glycol,” the identity and function of the excipients, the weight percentages, and whether the accused product uses wet granulation. The accused manufacturer’s ANDA, product-development records, batch records, and analytical data would be central evidence.
No settlement terms, authorized-generic arrangement, or launch license can be inferred from the claims supplied.
What generic launch scenarios exist?
Scenario 1: Same formulation architecture
A generic that copies the Rexulti inactive-ingredient system, coating, pigments, and wet-granulation method faces the highest risk. Otsuka could assert both composition and process claims.
Scenario 2: Different binder or lubricant
Replacing hydroxypropyl cellulose or magnesium stearate may avoid literal infringement of claim 1. The substituted formulation would still require FDA demonstration of pharmaceutical equivalence and bioequivalence.
Scenario 3: Different coating system
A coating based on an alternative polymer, different pigments, or polyethylene glycol could avoid one or more coating limitations. The product would need to satisfy FDA quality and performance requirements.
Scenario 4: Direct compression
Direct compression could avoid claims 3, 6, and 7 if no wet-granulated substance is used. It would not automatically avoid claim 1, which is directed to the finished tablet.
Scenario 5: Challenge to validity
A Paragraph IV applicant could challenge anticipation, obviousness, written description, enablement, indefiniteness, or enforceability. The use of common excipients creates a potential obviousness issue, but the patent’s specific combination, ranges, coating limitations, and technical results would determine the strength of that defense.
How does Patent 10,307,419 compare with a compound patent?
| Issue |
Compound patent |
Patent 10,307,419 |
| Protected subject |
Brexpiprazole molecule or chemical class |
Coated brexpiprazole tablet |
| Design-around potential |
Low if active ingredient is required |
Higher |
| Relevance to all dosage forms |
Usually broad |
Limited to claimed tablet |
| Manufacturing evidence |
Often less important |
Important for process claims |
| Generic risk |
High while valid and unexpired |
Product-specific |
| Typical challenge |
Chemical prior art and obviousness |
Formulation obviousness, claim scope, and non-infringement |
| Commercial effect |
Can block use of the active ingredient |
Can force a different formulation or delay launch |
Patent 10,307,419 can add launch risk after a compound patent expires, but it does not independently prevent a generic from using brexpiprazole in every formulation.
What are the geographic and manufacturing barriers?
The patent is a U.S. right. It can be asserted against U.S. manufacture, importation, sale, or offer for sale of a covered tablet. It does not automatically protect Rexulti formulations in Europe, Japan, Canada, or other jurisdictions.
International risk must be assessed patent by patent because corresponding applications may have different:
- claim scope;
- prosecution outcomes;
- expiration dates;
- opposition histories;
- national-phase status;
- patent-term adjustments;
- supplementary protection certificates.
For a U.S. generic manufactured overseas, importation of a product made by a process covered by an issued U.S. process claim can create separate exposure under 35 U.S.C. §271(g), subject to statutory limitations. The composition claims can also apply to imported tablets sold in the United States.
Key Takeaways
- U.S. Patent 10,307,419 is a formulation and manufacturing patent for brexpiprazole tablets, not a broad compound patent.
- Claim 1 requires a specific combination of active ingredient, excipients, hydroxypropyl cellulose, selected disintegrants, magnesium stearate, and a pigment-containing HPMC/talc coating.
- The coating must substantially exclude polyethylene glycol.
- Claims 6 and 7 add wet granulation, compression, and coating-process limitations.
- Claim 4 excludes povidone and crospovidone, while claim 5 defines the most specific lactose/corn-starch/microcrystalline-cellulose embodiment.
- The strongest generic design-around options involve changing the binder, lubricant, disintegrant, coating system, pigments, or manufacturing route.
- A non-infringing manufacturing process does not avoid liability if the finished tablet infringes claim 1.
- Orange Book listing and Paragraph IV status must be determined from the current FDA and litigation records, not from the patent claims alone.
- The patent has meaningful product-specific value but does not prevent all brexpiprazole formulations.
- Generic launch risk depends on the relationship between the ANDA formulation and the claimed inactive-ingredient and coating architecture.
FAQs
Does Patent 10,307,419 cover all Rexulti tablets?
No. It covers tablets that satisfy the patent’s combined active-ingredient, excipient, binder, disintegrant, lubricant, coating, pigment, and PEG-exclusion limitations.
Can a generic avoid the patent by using povidone?
Povidone may avoid dependent claim 4 and could also avoid claim 1 if it replaces the required hydroxypropyl cellulose binder. The complete formulation must still be compared against every limitation.
Does the patent cover brexpiprazole capsules or liquid formulations?
The supplied claims are directed to tablets and tablet-production methods. Capsules and liquid formulations fall outside the literal scope of these claims unless another claim or legal theory applies.
Is polyethylene glycol required in the generic coating?
No. The patent requires that the coating substantially not contain polyethylene glycol. A generic using polyethylene glycol may avoid that limitation, subject to the technical meaning of “substantially” and the remaining claim elements.
Can direct compression avoid the patent?
Direct compression can potentially avoid the wet-granulation process claims. It does not necessarily avoid claim 1, which covers the composition of the finished coated tablet.
References
- U.S. Patent and Trademark Office. (2019). U.S. Patent No. 10,307,419, tablet comprising 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one.
- U.S. Food and Drug Administration. (2015). Rexulti (brexpiprazole) prescribing information.
- U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- U.S. Food and Drug Administration. (n.d.). Hatch-Waxman amendments and abbreviated new drug applications.
- United States Code. 35 U.S.C. §§ 154, 271, 271(g), and 271(e).
