US Patent 10,195,210: Remimazolam Sedation Claims, Orange Book Scope, Expiry and Generic Risk

US Patent 10,195,210 protects procedure-specific use of intravenous remimazolam, particularly fixed-dose sedation administered before or during upper gastrointestinal endoscopy and colonoscopy. The patent does not claim remimazolam as a chemical compound, a general pharmaceutical composition, or a manufacturing process. Its commercial significance is tied to Byfavo, the FDA-approved remimazolam besylate product marketed by PAION and its U.S. commercial partners.

The strongest claim concentration is in three independent method claims:

Claim 1: intravenous fixed-dose remimazolam sedation combined with passage of an endoscope.
Claim 19: the same method using the besylate salt and a 2 mg to 10 mg fixed dose.
Claim 32: administration of 5 mg remimazolam followed by passage of a colonoscope.

The patent is therefore a method-of-use patent directed to procedural sedation, with dependent claims narrowing the scope by patient age, opioid pretreatment, procedure type, dose, administration time, sedation score and salt form.

What drug does US Patent 10,195,210 protect?

US Patent 10,195,210 covers remimazolam, specifically the compound 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.

The active pharmaceutical ingredient is remimazolam. Claim 18 and independent claim 19 expressly include the besylate salt, which is the form used in Byfavo.

Patent element	Commercial relevance
Active ingredient	Remimazolam
Salt expressly claimed	Remimazolam besylate
Product	Byfavo
FDA sponsor at approval	Acacia Pharma Inc.
Current commercial rights context	PAION remimazolam franchise and licensed U.S. commercialization
Dosage form	Intravenous injection
Therapeutic use	Procedural sedation
Covered procedures	Endoscopy, upper GI endoscopy and colonoscopy
Patent type	Method of treatment and method of use
Biologic or small molecule	Small molecule

The claims do not cover every use of remimazolam. A manufacturer using remimazolam for general anesthesia, intensive-care sedation or another procedure would need to analyze separate patents and claims.

What are the independent claims in US Patent 10,195,210?

Claim 1: intravenous fixed-dose endoscopic sedation

Claim 1 requires all of the following:

A subject undergoing a procedure involving sedation.
Intravenous administration.
One or more fixed doses.
An amount sufficient to sedate the subject.
A pharmaceutical composition containing remimazolam or a pharmaceutically acceptable salt.
Passage of an endoscope into the subject.

The claim is broad as to the precise endoscopic procedure. Claims 5 and 6 narrow it to upper GI endoscopy and colonoscopy, but claim 1 itself is not limited to those two procedures.

The term “fixed dose” is commercially important. The claim is directed to predetermined dose units rather than an open-ended titration protocol. The claim does not state that only one dose may be used. It covers one or more fixed doses.

Claim 19: remimazolam besylate and a 2 mg to 10 mg dose

Claim 19 narrows claim 1 in two material ways:

The pharmaceutical composition must contain remimazolam besylate.
Each fixed dose must contain approximately 2 mg to approximately 10 mg of the besylate salt.

The claim still requires intravenous administration and passage of an endoscope. It also retains the broad “procedure involving sedation” language.

For an authorized generic or ANDA applicant copying the Byfavo formulation and labeled endoscopic use, claim 19 is the principal direct-use claim of concern.

Claim 32: 5 mg colonoscopy method

Claim 32 requires:

One or more doses;
Each dose containing 5 mg of remimazolam or a pharmaceutically acceptable salt; and
Passage of a colonoscope into the subject.

Unlike claims 1 and 19, claim 32 does not expressly recite intravenous administration. It also does not expressly repeat the phrase “amount sufficient to sedate the subject” in the body of the claim, although the preamble describes a procedure involving sedation.

Claim 32 is narrower as to procedure and dose but potentially broader as to route of administration. Its practical relevance is highest for a 5 mg remimazolam colonoscopy protocol.

How do the dependent claims narrow patent 10,195,210?

The dependent claims create several alternative infringement paths.

Claims	Limitation	Scope
2, 20	Subject is at least 18 years old	Adult procedural sedation
3, 21	Opioid administered before remimazolam	Combination protocol
4, 22	Opioid is fentanyl	Common endoscopy regimen
5, 23	Upper GI endoscopy	Esophagogastroduodenoscopy-type procedures
6, 24	Colonoscopy	Lower GI endoscopy
7, 25	Dose administered over one minute or less	Rapid IV administration
8, 26	Approximately 2 mg to 10 mg per fixed dose	Broad dose range
9, 27	Approximately 3 mg to 10 mg	Intermediate range
10, 28	Approximately 3 mg to 9 mg	Narrower range
11	Approximately 5 mg to 9 mg	Clinically relevant range
12-15	Alternative dose wording and ranges	Formulation or dose-unit variants
16, 30	Approximately 5 mg	Core initial-dose use
17, 31	MOAA/S score of 4 or less	Sedation-depth limitation
18	Besylate salt	Byfavo-specific salt limitation
33-35	Diagnostic procedure	Diagnostic endoscopy use

The patent has a deliberate claim ladder. A competitor may avoid one dependent claim while still facing claim 1, claim 19 or claim 32. For example, eliminating fentanyl pretreatment does not avoid the core endoscopy claims. Changing the dose from 5 mg to 6 mg may avoid claim 16 but remain within claims 8 through 11.

What formulations are protected by US Patent 10,195,210?

The patent protects use of a pharmaceutical composition containing remimazolam or a pharmaceutically acceptable salt. Claim 19 is more commercially specific because it requires remimazolam besylate.

The claims do not appear to require a particular excipient, vial size, concentration, pH, preservative system or reconstitution solvent. The protection is therefore not a conventional formulation patent in the narrow sense. It is a use patent that reaches a formulation when the formulation is administered in the claimed procedural-sedation method.

Salt protection

Claim 18 covers a pharmaceutically acceptable salt through claim 1. Claim 19 independently specifies the besylate salt. A product containing a different remimazolam salt may avoid claim 19 but could remain within claim 1, depending on whether the salt is pharmaceutically acceptable and the other limitations are met.

Dose-unit protection

The principal dose ranges are:

Approximately 2 mg to 10 mg;
Approximately 3 mg to 10 mg;
Approximately 3 mg to 9 mg;
Approximately 5 mg to 9 mg;
Approximately 5 mg to 8 mg;
Approximately 5 mg.

These overlapping ranges make dose redesign a limited design-around strategy. A dose outside the stated ranges would still need to be tested against claim 1, which does not impose an express numerical dose limitation.

Does the patent cover fentanyl and remimazolam combination sedation?

Yes, claims 3, 4, 21 and 22 cover protocols in which an opioid is administered before remimazolam, including fentanyl.

The fentanyl limitation is dependent. Fentanyl pretreatment is not required for infringement of the independent claims. A procedure using remimazolam without fentanyl can still fall within claims 1, 19 or 32 if the remaining limitations are met.

The claims also do not require a particular fentanyl dose, route, timing interval or formulation. The relevant language is administration of one or more opioid doses before remimazolam.

What procedures are covered by the patent?

The patent’s direct procedural focus is endoscopy.

Upper GI endoscopy

Claims 5 and 23 cover upper GI endoscopy. These claims address procedures in which an endoscope is passed through the upper gastrointestinal tract.

Colonoscopy

Claims 6 and 24 expressly cover colonoscopy. Claim 32 separately targets passage of a colonoscope with 5 mg remimazolam.

Diagnostic procedures

Claims 33, 34 and 35 add diagnostic procedures to the independent claim structures. This is significant because it removes a possible distinction between therapeutic endoscopy and diagnostic endoscopy.

The patent does not appear limited to procedures performed in a hospital operating room. The claim language is functional and procedure-based. Ambulatory endoscopy centers, hospital outpatient departments and similar facilities may fall within the commercial risk analysis when the claimed remimazolam protocol is used.

What is the role of the MOAA/S score limitation?

Claims 17 and 31 require a Modified Observer’s Assessment of Alertness/Sedation score, or MOAA/S score, of less than or equal to 4.

This limitation narrows the claims to a defined level of sedation. It may be relevant in litigation because the patentee would need to establish that the claimed sedation endpoint was achieved. A protocol could raise factual issues if:

Sedation depth is not measured;
The patient remains at a MOAA/S score above 4;
The score is recorded only intermittently;
The protocol uses a different sedation scale; or
The dose is administered for analgesia or anxiolysis without achieving the claimed endpoint.

The MOAA/S limitation does not restrict the independent claims. It is an added limitation available for narrower enforcement.

When does US Patent 10,195,210 expire?

The patent issued on February 5, 2019. Its statutory term is generally measured from the effective nonprovisional or international filing date, subject to patent-term adjustment and any terminal disclaimer. The patent’s Orange Book-listed expiry should control Hatch-Waxman planning rather than an unadjusted term calculation.[1][2]

For commercial planning, the patent is generally treated as an approximately 2034-2035 remimazolam use patent, subject to the USPTO-calculated patent-term adjustment and the FDA Orange Book entry.

Milestone	Date or status
Patent grant	February 5, 2019
Patent number	US 10,195,210
FDA Byfavo approval	July 1, 2020
Primary indication	Induction and maintenance of procedural sedation in adults
Expected patent protection period	Through the mid-2030s, subject to official term calculation
Regulatory exclusivity	NDA exclusivity is separate from patent term

The patent should not be confused with the FDA’s five-year new chemical entity exclusivity. FDA approval of Byfavo occurred in 2020, while the patent term extends beyond the initial regulatory exclusivity period.

What is the Orange Book status of US Patent 10,195,210?

US Patent 10,195,210 is associated with Byfavo’s procedural-sedation protection and is the type of method-of-use patent that may be listed in the FDA Orange Book with a use code tied to procedural sedation.

An Orange Book listing does not automatically block every generic remimazolam product. It affects ANDA certification and labeling strategy:

A Paragraph III certification accepts the listed patent and delays approval until patent expiry.
A Paragraph IV certification asserts that the patent is invalid, unenforceable or not infringed.
A section viii statement may seek approval with the patented method omitted, if the remaining label does not promote the protected use.

Because the claims are directed to endoscopic sedation, a generic applicant may attempt a skinny label excluding colonoscopy and upper GI endoscopy. That strategy would be commercially meaningful only if the proposed labeling, promotional materials and distribution practices do not encourage the patented use.

Which companies are challenging US Patent 10,195,210?

No publicly established Paragraph IV litigation against US Patent 10,195,210 is identified in the cited FDA and public patent records. The absence of an identified case does not establish that no ANDA certification has been filed; ANDA certifications are not always fully visible before litigation.

The likely challenger categories are:

Generic injectable-drug manufacturers filing ANDAs for remimazolam.
Contract manufacturers seeking an abbreviated or 505(b)(2) pathway.
Sponsors pursuing remimazolam for non-endoscopy indications.
Licensees seeking territory-specific rights outside the U.S.

A 505(b)(2) applicant may face patent-listing consequences similar to an ANDA applicant, but its strategy may differ if it relies on a different clinical indication, dosage regimen or route.

What Paragraph IV risks exist for remimazolam generics?

A Paragraph IV challenge would likely focus on four issues.

Claim construction

A challenger could contest the meaning of:

“fixed dose”;
“amount sufficient to sedate”;
“procedure involving sedation”;
“passing an endoscope”; and
“each fixed dose.”

The scope of claim 32 may receive particular attention because it does not expressly recite intravenous administration in the claim body.

Anticipation

A challenger would search prior art describing remimazolam administration during endoscopy or colonoscopy, especially fixed-dose protocols involving 5 mg doses, rapid administration and opioid pretreatment.

A reference would need to disclose every claim element arranged as claimed. General disclosures of remimazolam sedation, without the endoscope limitation or fixed-dose limitation, would not necessarily anticipate claims 1, 19 or 32.

Obviousness

The most plausible obviousness theory would combine:

Earlier remimazolam pharmacology;
Known benzodiazepine sedation protocols;
Endoscopy sedation practice;
Fentanyl pretreatment;
Fixed-dose IV administration; and
Dose-ranging studies.

The patentee would likely rely on clinical advantages such as rapid onset, predictable recovery and suitability for endoscopic procedures. The strength of the obviousness defense would depend on the specific prior art available before the relevant priority date and the evidence concerning dose selection and procedural performance.

Written description and enablement

The patent claims multiple dose ranges, salt forms, procedures and sedation endpoints. A challenger could argue that the specification does not adequately support the full breadth of the claims, particularly if the disclosure is concentrated on particular doses or procedure types.

The enablement analysis would consider whether a skilled person could practice the full claimed range without undue experimentation.

How strong is the patent estate for Byfavo?

The patent estate is strongest against a product that copies all of the following:

Remimazolam besylate;
Intravenous administration;
Fixed-dose delivery;
Adult procedural sedation;
Colonoscopy or upper GI endoscopy; and
A 5 mg or nearby dose.

The estate is weaker against products that pursue:

General anesthesia;
ICU sedation;
Pediatric sedation;
Non-endoscopic procedures;
A different route of administration;
A non-besylate salt; or
A label that omits the patented endoscopic use.

The patent is not a composition-of-matter patent. That distinction matters. Once the core compound patent and regulatory barriers expire or are overcome, a competitor may be able to commercialize remimazolam for unclaimed uses while still facing liability for a labeled endoscopic use.

How does this patent compare with compound and manufacturing patents?

Patent category	Typical protected subject matter	Relevance to US 10,195,210
Composition of matter	Remimazolam molecule	Not the subject of the asserted claims
Salt or solid form	Besylate, polymorph or crystalline form	Only salt use is expressly incorporated here
Formulation	Concentration, excipients, stability and reconstitution	Not specifically claimed in the supplied claims
Method of use	Endoscopic procedural sedation	Core subject of US 10,195,210
Manufacturing	Synthesis, purification and scale-up	Not claimed
Regulatory use	FDA-labeled procedural sedation	Aligns with Byfavo’s approved indication

A generic manufacturer may avoid manufacturing and composition claims but still face the method-of-use patent if its label includes procedural sedation for endoscopy.

What generic launch scenarios exist?

Scenario 1: Full-label generic launch

A generic product seeks the same procedural-sedation indication, including colonoscopy and upper GI endoscopy. This creates the highest risk of a Paragraph IV dispute and a 30-month stay if the statutory requirements for patent litigation are met.

Scenario 2: Skinny-label launch

The applicant removes patented endoscopic uses from the label. This reduces direct inducement risk but does not eliminate all risk. Marketing, distributor communications, clinical materials and physician instructions can affect an induced-infringement analysis.

Scenario 3: Non-endoscopy indication

A sponsor develops remimazolam for general anesthesia or another use. The product may avoid the supplied claims, but separate remimazolam patents must be reviewed.

Scenario 4: Alternative dose or salt

A different dose or salt may avoid certain dependent claims. It is unlikely to provide a complete design-around without separate analysis of the broader independent claims.

What licensing deals affect remimazolam commercialization?

PAION developed remimazolam and licensed regional rights to commercial partners. Acacia Pharma held U.S. commercialization rights for Byfavo at FDA approval, and PAION later became the principal corporate owner of the remimazolam commercial program after acquiring Acacia’s business in 2023.[3][4]

The licensing structure matters because patent enforcement, Orange Book strategy and settlement authority may differ from the entity named as patent assignee. A freedom-to-operate review should identify:

The current patent owner;
Exclusive U.S. licensees;
Any sublicense rights;
The NDA holder;
The entity controlling Orange Book submissions; and
Any assignment recorded with the USPTO.

Does biosimilar risk apply to Byfavo?

No. Remimazolam is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an ANDA or, in some cases, a 505(b)(2) application. Biosimilar provisions under the Public Health Service Act do not apply.

The principal regulatory and patent risks are therefore:

Paragraph IV certification;
Section viii labeling;
Patent-term timing;
Method-of-use litigation; and
Formulation or manufacturing patent review.

Key Takeaways

US Patent 10,195,210 is a method-of-use patent for remimazolam procedural sedation involving endoscope passage.
Claims 1, 19 and 32 are the core independent claims.
Claim 19 is particularly relevant to Byfavo because it expressly covers remimazolam besylate in a 2 mg to 10 mg fixed dose.
Claim 32 targets a 5 mg colonoscopy protocol.
Fentanyl pretreatment, rapid administration and MOAA/S scoring are dependent limitations, not requirements of every independent claim.
The patent does not claim remimazolam itself, a general formulation or a manufacturing process.
FDA approval of Byfavo occurred July 1, 2020 for procedural sedation in adults.
Generic risk is highest for a full-label product that includes colonoscopy and upper GI endoscopy.
A skinny-label or non-endoscopy strategy may reduce infringement exposure but requires careful review of promotional conduct.
Remimazolam has generic, not biosimilar, competitive risk.
The patent is expected to remain relevant through the mid-2030s, subject to the official USPTO and Orange Book term records.

FAQs

Is US Patent 10,195,210 a composition-of-matter patent?

No. The supplied claims are treatment-method claims. They cover specified remimazolam sedation procedures rather than the remimazolam molecule in all uses.

Does a 5 mg remimazolam dose always infringe the patent?

No. A 5 mg dose is specifically addressed by dependent claims and claim 32, but infringement also depends on the procedure, endoscope or colonoscope use, route, dosing structure and other claim elements.

Can a generic remimazolam product omit colonoscopy from its label?

Potentially. A section viii or skinny-label strategy may omit patented indications, but the resulting label and promotional conduct must be evaluated against the asserted method-of-use claims.

Does the patent cover pediatric procedural sedation?

The independent claims are not expressly limited to adults, but claims 2 and 20 add an adult limitation. FDA’s Byfavo indication is for adults, and pediatric use raises separate regulatory and infringement questions.

Does US Patent 10,195,210 cover remimazolam for general anesthesia?

Not based on the supplied claims. The claims require an endoscope or colonoscope to be passed into the subject. General-anesthesia uses without the claimed endoscopic procedure fall outside these claim limitations, subject to other remimazolam patents.

References

U.S. Patent and Trademark Office. (2019). U.S. Patent No. 10,195,210, methods for conducting a procedure involving sedation.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2020, July 1). FDA approves Byfavo for procedural sedation in adults.
PAION AG. (2023). Annual report 2023 and remimazolam commercialization disclosures.

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	10,195,210	⤷ Start Trial				USE OF REMIMAZOLAM FOR INDUCTION AND MAINTENANCE OF PROCEDURAL SEDATION IN ADULTS UNDERGOING PROCEDURES LASTING 30 MINUTES OR LESS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011328497	⤷ Start Trial
China	103347519	⤷ Start Trial
Denmark	2637662	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,195,210