Details for Patent: 9,827,251

Which drugs does patent 9,827,251 protect, and when does it expire?

Patent 9,827,251 protects BYFAVO and is included in one NDA.

This patent has twenty-one patent family members in sixteen countries.

Summary for Patent: 9,827,251

Title:	Dosing regimen for sedation with CNS 7056 (remimazolam)
Abstract:	The invention relates to a dosing regimen for sedation with the fast-acting benzodiazepine CNS 7056 in combination with an opioid, in particular fentanyl, whereas CNS 7056 is given in a dose of 2 to 20 mg, preferably between 4 and 9 mg and most preferably between 5 and 8 mg.
Inventor(s):	Karin Wilhelm-Ogunbiyi, Keith Borkett, Gary Stuart Tilbrook, Hugh Wiltshire
Assignee:	Paion UK Ltd
Application Number:	US15/647,143
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,827,251
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 9,827,251: Remimazolam Fixed-Dose Sedation Claims, Expiration, Orange Book Status, and Generic Risk

US Patent 9,827,251 protects intravenous sedation using remimazolam besylate, marketed in the United States as Byfavo. Its central limitation is administration of one or more fixed doses that do not depend on patient body weight. The claims also cover adult patients, procedural sedation, rapid intravenous administration, opioid pretreatment, specific dose ranges, colonoscopy, upper-GI endoscopy, and target MOAA/S sedation scores.

The patent is a method-of-use patent, not a broad composition patent. It does not independently cover remimazolam besylate as a chemical compound or every possible use of the active ingredient.

What drug and active ingredient does US Patent 9,827,251 cover?

The patent covers the besylate salt of remimazolam, chemically identified in the claims as:

3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester.

Remimazolam is an ultra-short-acting benzodiazepine used for intravenous procedural sedation. The approved product is remimazolam besylate injection, marketed as Byfavo by Cosmo Pharmaceuticals’ U.S. commercial organization following FDA approval in 2020.

Attribute	Details
Active ingredient	Remimazolam
Salt form claimed	Besylate
Brand	Byfavo
Dosage form	Intravenous injection
Therapeutic category	Procedural sedation
FDA application	NDA 214998
Patent type	Method of treatment and dosing
Primary limitation	Fixed dose independent of body weight
Key procedures	Colonoscopy and upper-GI endoscopy
Sedation metric	MOAA/S score of 4 or less

The claims are directed to administering the salt, rather than merely administering remimazolam in any form. A product using a different salt, prodrug, or chemically distinct formulation would require separate analysis.

What are the independent claims of US 9,827,251?

The patent has two independent method claims.

Claim 1: Fixed-dose procedural sedation

Claim 1 requires:

1. A subject undergoing a procedure.
2. Intravenous administration.
3. One or more fixed doses.
4. A composition containing remimazolam besylate.
5. An administered amount that does not depend on body weight.

This claim is broad as to the procedure. The procedure need not be a colonoscopy or endoscopy for claim 1 to apply. It also does not expressly require the patient to be an adult, use of fentanyl, a particular MOAA/S score, or a particular dose range.

Claim 17: Adult diagnostic or therapeutic procedures

Claim 17 narrows the method by requiring that:

• The subject is undergoing a diagnostic or therapeutic procedure.
• The subject is at least 18 years old.
• The administered amount does not depend on body weight.
• The drug is administered intravenously in one or more fixed doses.

Claim 17 is narrower than claim 1 because it expressly requires an adult subject and a diagnostic or therapeutic procedure. It may nevertheless be commercially important because the FDA-approved use of Byfavo is centered on adult procedural sedation.

How do the dependent claims narrow the patent scope?

The dependent claims create overlapping protection around the main commercial use of Byfavo.

Claim	Limitation
2	Fixed dose of about 2 mg to about 10 mg
3	About 3 mg to about 10 mg
4	About 3 mg to about 9 mg
5	About 5 mg to about 8 mg
6	Subject is at least 18 years old
7	Opioid administered before remimazolam
8	Opioid is fentanyl
9	Dose produces MOAA/S score of 4 or less
10	MOAA/S score is 1 to 4
11	MOAA/S score is 2 to 4
12	Procedure is diagnostic
13	Procedure is colonoscopy
14	Procedure is upper-GI endoscopy
15	Upper-GI endoscopy is therapeutic
16	Each dose is administered over one minute or less
18	Adult diagnostic or therapeutic procedure, rapid administration, MOAA/S of 4 or less
19	Procedure is colonoscopy
20	Dose is about 2 mg to 10 mg

The claim set uses nested dose ranges. A method using 6 mg falls within claims 2, 3, 4, and 5, assuming all other limitations are satisfied. A method using 2 mg falls within claim 2 but not claims 3 through 5.

What is the core patent scope?

The core scope is the combination of remimazolam besylate and a weight-independent fixed-dose regimen for intravenous procedural sedation.

The patent does not require:

• A specific vial concentration.
• A particular reconstitution volume.
• A specific maintenance-dose schedule.
• A particular dosing interval between repeat doses.
• Use of an infusion pump.
• A specific opioid other than where claim 8 is asserted.
• A specific procedure under claim 1.
• A particular MOAA/S score under claim 1.

The phrase “does not depend on the body weight” is the principal construction issue. A regimen may remain fixed even if clinicians consider other factors, such as age, comorbidities, procedure duration, or concomitant drugs. A regimen that expressly calculates the dose from kilograms of body weight presents a stronger non-infringement position against the fixed-dose limitation, although the overall product label and actual prescribing instructions would remain relevant.

What formulations are protected by US 9,827,251?

The patent protects use of a composition containing remimazolam besylate. It does not, based on the provided claims, require a particular excipient system, pH, buffer, concentration, container, lyophilized cake, or reconstitution solvent.

Formulation limitations

The claims cover a composition containing the besylate salt, but the claim language does not expressly define:

• Remimazolam concentration.
• Excipient identity.
• pH range.
• Osmolality.
• Preservative content.
• Container closure.
• Ready-to-use versus reconstituted presentation.
• Stability period.
• Manufacturing process.

Those features may be protected by separate formulation or manufacturing patents in the Byfavo patent family or related patent families. They should not be attributed to US 9,827,251 without a separate claim review.

When does US Patent 9,827,251 expire?

The patent issued on November 28, 2017. Its ordinary patent term is expected to run from the relevant nonprovisional application filing date to approximately December 2032, subject to any patent-term adjustment, patent-term extension, disclaimer, or terminal-disclaimer effect recorded in the USPTO file history.[1]

Milestone	Date
Patent issued	November 28, 2017
Patent number	US 9,827,251 B2
Expected ordinary term endpoint	Approximately December 2032
Regulatory patent extension	Requires separate USPTO and FDA verification
Pediatric exclusivity	Requires current Orange Book verification

The expiration date should be treated as the date recorded after reviewing the USPTO patent term data and the Orange Book listing. A patent’s issue date does not determine its expiration date.

What is the Orange Book status of remimazolam and Byfavo?

Byfavo was approved by FDA in July 2020 for induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.[2] FDA’s Orange Book is the controlling public source for listed patents and FDA-approved use codes.[3]

US 9,827,251 is relevant to Orange Book analysis because its claims correspond closely to the approved use of intravenous remimazolam for adult procedural sedation. The practical impact depends on:

• Whether the patent is listed against NDA 214998.
• The applicable use code.
• Any later-listed continuation or formulation patents.
• Whether a generic applicant challenges the listing under Paragraph IV.
• Whether a generic applicant can use a section viii statement or omit the patented use from its labeling.

An Orange Book listing does not prove infringement. It creates a statutory framework for notice, litigation, and potential 30-month approval delay under the Hatch-Waxman Act.[4]

What Paragraph IV challenges and generic entry risks exist?

A generic remimazolam applicant could file an ANDA with one of four certifications:

1. No patent information has been filed.
2. The patent has expired.
3. The applicant will not market before patent expiration.
4. The patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV challenge to US 9,827,251 would likely focus on the fixed-dose, weight-independent limitation and the relationship between the patent claims and the FDA-approved label.

Potential design-around strategies

A generic applicant could seek to reduce risk through:

• A label that directs weight-based dosing.
• A label omitting the patented procedural-sedation use, if clinically and regulatorily feasible.
• A different salt or formulation, if the product remains pharmaceutically and clinically acceptable.
• A dosing protocol that requires patient-specific calculations.
• A product that does not instruct administration within one minute.
• A product label excluding colonoscopy or upper-GI endoscopy.

These strategies may not avoid infringement if physicians routinely use the generic for the patented method and the manufacturer induces that use through labeling, promotional activity, or dosing instructions.

How strong is the patent estate for remimazolam?

US 9,827,251 has meaningful commercial strength because it maps onto the central dosing concept used for procedural sedation: fixed intravenous dosing rather than a conventional weight-based benzodiazepine regimen.

Strengths

• It covers the active pharmaceutical ingredient used in Byfavo.
• It targets the approved adult procedural-sedation market.
• Claim 1 is not limited to colonoscopy or endoscopy.
• The dose-dependent claims create fallback positions.
• Claims 13, 14, and 19 align with high-volume endoscopic procedures.
• The claims cover rapid administration and clinically defined sedation depth.

Vulnerabilities

• The patent does not claim the remimazolam molecule itself.
• The fixed-dose limitation may create a design-around path.
• “About” dose ranges may generate claim-construction disputes.
• The method claims require proof of the claimed administration method.
• A generic applicant may argue that the fixed-dose regimen was obvious in view of prior remimazolam clinical studies and conventional procedural-sedation dosing.
• A manufacturer may attempt to omit or modify the patented use from its label.

The strongest claims from a commercial perspective are claims 1, 17, 13, 14, 18, and 19. Claims 2 through 5 and 20 provide dose-range coverage but may be more vulnerable if prior art discloses overlapping doses.

How does US 9,827,251 compare with composition and formulation patents?

Patent category	What it protects	Generic risk
Composition patent	Remimazolam or a defined chemical form	Blocks use of the claimed molecule or salt until expiry
Salt patent	Besylate or another pharmaceutically acceptable salt	May require a different salt or challenge salt selection
Formulation patent	Concentration, excipients, stability, container, or reconstitution	Can block a commercially practical injectable presentation
Method-of-use patent	Sedation method, dosing regimen, patient group, or procedure	May permit a non-infringing label or clinical-use strategy
Manufacturing patent	Synthetic process, purification, crystallization, or scale-up	Can increase cost and limit supply options

US 9,827,251 is principally in the last two categories, with its primary value arising from method-of-use protection rather than molecular exclusivity.

What FDA regulatory exclusivity applies to Byfavo?

FDA approved Byfavo under the new drug application pathway, not the biologics license application pathway. Remimazolam is a small molecule, so a later applicant would generally pursue an ANDA or, depending on the product and evidence, a 505(b)(2) application.

Regulatory exclusivity is distinct from patent exclusivity. FDA approval in 2020 may have provided new-drug exclusivity, but that period is separate from the patent term and does not replace Orange Book patent protection.[2] A later applicant may face:

• Patent certification requirements.
• Clinical bridging and bioequivalence questions.
• Injectable-product chemistry, manufacturing, and controls review.
• Sterility and container-closure requirements.
• Labeling restrictions for patented procedural-sedation uses.

Biosimilar risk is not the relevant framework. Remimazolam is a chemically synthesized small molecule, not a biologic.

What patent litigation affects remimazolam?

The supplied claim set does not establish a current litigation position. Patent litigation risk should be assessed through PACER, PTAB records, USPTO prosecution histories, and FDA Paragraph IV notices.

The principal disputes likely to arise from this patent would concern:

• Whether a proposed regimen is truly fixed.
• Whether “does not depend on body weight” is satisfied.
• Whether administration over one minute or less occurs in routine clinical use.
• Whether a generic label induces the patented procedural-sedation use.
• Whether overlapping dose ranges were obvious.
• Whether the claims are enabled across the full range of claimed procedures and doses.

A validity challenge could raise anticipation, obviousness, written-description, enablement, indefiniteness, or double-patenting arguments. A method claim also creates proof issues because infringement may depend on clinical administration rather than solely on product composition.

What licensing deals affect Byfavo commercialization?

PAION developed remimazolam and entered commercial arrangements for regional development and commercialization. In the United States, Byfavo commercialization has been associated with Cosmo Pharmaceuticals and its commercial operations. Licensing rights, royalty obligations, and control of patent enforcement depend on the applicable agreements and amendments.[5]

Commercial diligence should separate:

• Patent ownership.
• NDA ownership.
• U.S. commercialization rights.
• Royalty-bearing territories.
• Enforcement rights.
• Sublicense rights.
• Rights to continuation patents.
• Rights to settlement proceeds or Paragraph IV litigation.

A licensee may commercialize Byfavo without owning every relevant patent, while the patent owner may retain prosecution or enforcement control.

What generic launch scenarios exist after patent expiry?

Scenario 1: No Paragraph IV challenge

A generic applicant waits for patent expiry or files certifications that do not trigger litigation. Entry could occur after regulatory approval and expiration of listed patents and exclusivity.

Scenario 2: Paragraph IV litigation

The NDA holder or patent owner sues within the statutory period. FDA approval may be delayed by the 30-month stay unless the case is resolved earlier or the stay is altered by court action.

Scenario 3: Skinny-label entry

A generic applicant removes patented procedural-sedation uses from its labeling. This strategy depends on whether FDA permits the omitted use and whether actual market behavior creates induced-infringement exposure.

Scenario 4: 505(b)(2) entry

A sponsor develops a product or labeling package that differs materially from the reference product. This route may face patent certifications and does not automatically avoid method-of-use patents.

Scenario 5: Post-expiry competition

After all relevant patents and exclusivities expire, competition will likely focus on sterile manufacturing capacity, hospital contracting, anesthesia-provider adoption, drug shortages, supply reliability, and price.

What is the revenue exposure from US 9,827,251?

The patent’s revenue exposure is concentrated in adult procedural sedation, especially gastrointestinal endoscopy. Its economic value depends on:

• Byfavo U.S. net sales.
• The proportion of sales attributable to colonoscopy and upper-GI procedures.
• The existence of later-expiring formulation or manufacturing patents.
• The timing of generic or 505(b)(2) competition.
• Hospital and ambulatory surgery center adoption.
• Reimbursement and drug-acquisition economics.

Because US 9,827,251 does not claim the compound itself, its blocking power may be lower than a core composition patent but higher than a narrow indication patent if the approved label and clinical practice use fixed dosing.

Key Takeaways

• US 9,827,251 protects intravenous fixed-dose sedation with remimazolam besylate.
• The principal limitation is that dosing does not depend on patient body weight.
• The patent covers adult procedural sedation, diagnostic and therapeutic procedures, colonoscopy, upper-GI endoscopy, rapid administration, fentanyl pretreatment, and MOAA/S outcomes through dependent claims.
• The expected ordinary term runs to approximately December 2032, subject to USPTO-recorded adjustments or disclaimers.
• The patent is a method-of-use patent, not a broad composition patent.
• Generic risk centers on Paragraph IV validity challenges, label carve-outs, and weight-based dosing design-arounds.
• Biosimilar pathways do not apply because remimazolam is a small molecule.
• The commercial blocking position must be assessed with the full Orange Book listing, continuation patents, formulation patents, manufacturing patents, and any licensing agreements.

FAQs About US Patent 9,827,251

Does US 9,827,251 cover all remimazolam products?

No. The claims require the besylate salt and a specified intravenous sedation method. They do not independently claim every remimazolam formulation, salt, route, or therapeutic use.

Can a generic remimazolam product avoid the patent by using weight-based dosing?

Potentially. A genuinely weight-based label may avoid the express fixed-dose limitation, but induced infringement, clinical-use evidence, other patents, and the precise wording of the generic label would remain relevant.

Does the patent cover sedation for pediatric patients?

Claim 1 is not expressly limited to adults. Claims 6, 17, and 18 require or incorporate adult-patient limitations. Pediatric use must be analyzed claim by claim.

Is Byfavo protected by a biosimilar exclusivity period?

No. Byfavo contains a small-molecule active ingredient and is regulated through the NDA and ANDA framework rather than the biologic and biosimilar framework.

What is the most commercially important claim in US 9,827,251?

Claim 1 is the broadest independent claim because it covers intravenous fixed-dose remimazolam besylate sedation without limiting the procedure, patient age, dose range, or sedation score. Claim 17 is narrower but closely aligned with adult diagnostic and therapeutic procedural sedation.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,827,251, methods of sedation using remimazolam. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (2020). Byfavo (remimazolam) prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.

5. PAION AG. (2023). Annual report and commercial licensing disclosures. PAION AG.

Drugs Protected by US Patent 9,827,251

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Acacia	BYFAVO	remimazolam besylate	POWDER;INTRAVENOUS	212295-001	Oct 6, 2020		RX	Yes	Yes						USE OF REMIMAZOLAM FOR INDUCTION AND MAINTENANCE OF PROCEDURAL SEDATION IN ADULTS UNDERGOING PROCEDURES LASTING 30 MINUTES OR LESS

Foreign Priority and PCT Information for Patent: 9,827,251

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	10014366	Nov 8, 2010
	10014784	Nov 19, 2010
	10014819	Nov 22, 2010
	10014972	Nov 25, 2010

International Family Members for US Patent 9,827,251

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011328497
China	103347519
Denmark	2637662
Eurasian Patent Organization	024926
Eurasian Patent Organization	201390672
European Patent Office	2450039
European Patent Office	2637662