Scope and claims of U.S. Patent 8,057,811 and the US clozapine suspension patent landscape

U.S. Patent 8,057,811 claims and methods cover a physicochemically stable, buffered, wetting-agent containing clozapine aqueous suspension for oral administration, with pH maintained ~6 to ~11 (preferred ~6 to ~8), using specific wetting agents (propylene glycol, glycerin, polyethylene glycol) and specific stabilizers/suspending systems (xanthan gum, guar gum, tragacanth gum, HPMC, microcrystalline cellulose), and with optional preservatives (including methyl/parabens) and optional polyvinyl pyrrolidone (PVP). The claim set is broad on composition ingredients and parameter ranges, while method claims recite batch-processing steps that track how such suspensions are typically prepared.

What does U.S. Patent 8,057,811 claim for clozapine suspension stability?

Answer: It claims a clozapine-in-water suspension composition for oral administration with (i) a wetting agent, (ii) a polymeric or cellulosic stabilizer/suspending agent, (iii) a buffer that holds pH about 6–11 (often 6–8), and (iv) optional preservative and optional PVP, plus related preparation methods controlling pH and mixing order.

Core independent claim coverage (Claim 1)

Claim 1 is the principal scope anchor:

Drug form: “physicochemically stable aqueous composition for oral administration comprising clozapine in suspension”
Wetting agent (defined by list): one or more of
- propylene glycol
- glycerin
- polyethylene glycol
Stabilizing agent (defined by list): one or more of
- xanthan gum
- guar gum
- tragacanth gum
- hydroxypropyl methylcellulose (HPMC)
- microcrystalline cellulose
Buffer with pH specification: pH maintained about 6 to about 11
Implied structure: multi-component suspension with both wetting and stabilization functions plus buffered pH control to support “physicochemical stability.”

Practical claim breadth points

“Selected from any one or more of” makes the formulation composition-inclusive: using multiple wetting agents or multiple stabilizers still falls in scope.
The stabilizer list is closed (only those recited), so using a different suspending polymer (e.g., CMC alone, carbomers, HEC, PVP as stabilizer instead of as optional ingredient) is a design-around route unless it is functionally categorized into one of the listed materials.
The pH range is broad enough to cover multiple buffering systems, as long as the formulation is maintained within the stated pH window.

Key dependent claims that tighten or add limitations

Claim 2: buffer is sodium phosphate/sodium hydroxide buffer.
Claim 3: pH narrowed to about 6 to about 8.
Claim 4: clozapine amount ~0.1% to ~10% by weight.
Claim 5: wetting agent amount ~0.1% to ~15%.
Claim 6: composition may further include suspending agent and/or preservative.
Claim 7: preservative selected from methyl, propyl, butyl parabens.
Claim 8: explicit “example embodiment” listing clozapine + glycerine + sodium dihydrogen phosphate dihydrate/NaOH buffer + xanthan gum + methyl paraben + propyl paraben + water.
Claim 16: may include sweetening and/or flavoring agents.
Claim 17: explicit “example embodiment” using sodium methyl and propyl paraben with glycerin and specific buffer.
Claim 18: stability for at least 14 months (this is typically supported by data in the specification and becomes a useful validity and infringement hook if samples meet the benchmark).

Method claims: scope depends on step order and parameter control

Two method constructs are present:

Method for preparing by pH control (Claim 9–11)

Claim 9: method of preparing a physicochemically stable clozapine suspension composition according to Claim 1, with the method step of controlling pH between ~6 and ~11.
Claim 10: pH controlled 6–8.
Claim 11: method further includes addition of polyvinyl pyrrolidone (PVP).

This cluster can be read as a process limitation that tracks the composition claim’s pH requirement; infringement typically turns on whether the manufacturing process actually “includes” pH control into the stated range and whether PVP is added as recited.

Batch production steps (Claim 12–15)

Claim 12 (propylene glycol route):
- (a) stir clozapine with about three quarters of propylene glycol assigned to batch
- (b) add buffer salt (and optionally sweeteners) dissolved in about half the water assigned, constant stirring
- (c) adjust pH with base component with mixing
- (d) add preservatives dissolved in remaining propylene glycol
- (e) slow addition of suspending agent with continuous stirring until thickens
- (f) dilute with water to end-volume
Claim 13 (glycerine route): same logic with glycerine and specific sub-steps for preservatives dissolution (preservatives in a small volume of water rather than remaining glycerine).
Claim 14–15: PVP added as an aqueous solution following addition of suspending agent.

Method claim impact

The batch claims are not just “any method.” They recite a sequence and allocation concepts (e.g., “three quarters” wetting agent; “about half” water; preservative solubilization location). That can narrow infringement if a competitor uses different mixing order, different allocation, or adds preservative as a different stream.
Still, the independent process idea is consistent: pre-wet drug with a wetting agent, dissolve buffer components, adjust pH, introduce preservatives, add suspending agent gradually, then dilute.

Composition claim variant including PVP (Claim 19)

Claim 19 is a second composition claim that includes PVP explicitly:

clozapine suspension
wetting agent (propylene glycol or glycerin or polyethylene glycol)
polyvinyl pyrrolidone
buffer with pH ~6–11

This provides an additional infringement target for formulations including PVP.

How is the pH range and buffer selection used to define “physicochemically stable” clozapine suspensions?

Answer: The claims use pH as a primary stability parameter: the formulation is maintained between ~6 and ~11 and, in narrower dependents, ~6 to ~8. Buffer selection is broad in Claim 1 but specific in Claim 2 (sodium phosphate/sodium hydroxide) and illustrated by dihydrogen phosphate/NaOH.

Claim-driven pH boundary conditions

Claim 1: pH maintained about 6–11
Claim 3: pH maintained about 6–8
Method claims repeat the same pH control concepts:
- Claim 9: pH controlled about 6–11
- Claim 10: pH controlled 6–8

Buffer system narrowing

Claim 2: sodium phosphate/sodium hydroxide buffer.
Claim 8 and Claim 17 embed:
- “sodium dihydrogen phosphate dihydrate/NaOH buffer” (Claim 8 example)
- same buffer system (Claim 17 example)

A competitor using a different base/acid buffer system (e.g., citrate, acetate, borate) could still meet Claim 1’s general buffer requirement if the “buffer” maintains pH in-range and if the claim language does not limit buffer identity. But Claim 2 offers an additional hook when the competitor uses sodium phosphate/NaOH.

Stability duration as a claim element

Claim 18: stability “for at least 14 months.”

If 14-month stability is tied to test conditions in the specification, this becomes relevant in validity and infringement proof. Competitors may avoid by demonstrating stability below the stated duration, changing storage conditions, or using different excipient systems that fail the specific stability characterization.

Which formulation components are explicitly covered (wetting agents, stabilizers, preservatives, PVP) and which are not?

Answer: The claims explicitly cover listed wetting agents, listed stabilizers/suspending agents, optional parabens, optional PVP, and optional sweetening/flavoring. Unlisted polymers or preservative classes can fall outside literal claim scope.

Wetting agents covered

From Claim 1 and Claim 19:

propylene glycol
glycerin
polyethylene glycol

Stabilizing agents / suspending polymers covered

From Claim 1:

xanthan gum
guar gum
tragacanth gum
hydroxypropyl methylcellulose
microcrystalline cellulose

Not covered literally (unless they are also one of the above materials):

carbomer/crosslinked polymers
sodium CMC (unless positioned as “microcrystalline cellulose,” which it is not)
hydroxyethyl cellulose (HEC)
povidone as stabilizer (but PVP is explicitly added in Claim 19 and Claim 11/14–15 as an optional component)

Preservatives covered

From Claim 7:

methyl paraben
propyl paraben
butyl paraben

Only these are explicitly listed.

PVP usage

Claim 11: method includes addition of PVP
Claim 14–15: PVP added after suspending agent
Claim 19: composition includes PVP

This creates a specific claim pathway for formulations that incorporate PVP.

Sweeteners and flavors

Claims 16, 12(b) and 13(b) allow optional sweeteners/flavoring. This is unlikely to narrow infringement because it is optional.

What do the process step limitations in Claim 12–15 require for infringement risk?

Answer: To fall within Claims 12–15, a process likely must (i) pre-mix clozapine with about three quarters of the wetting agent (propylene glycol or glycerine depending on route), (ii) dissolve buffer salts in about half the water, (iii) adjust pH with the buffer base component, (iv) add preservatives in a specific phase (propylene glycol in Claim 12; small volume water in Claim 13), (v) add suspending agent slowly while mixing until thickening, and (vi) dilute to final volume.

Sequence and allocation details

“About three quarters of” the wetting agent during initial mixing is explicit.
“Buffer salt … dissolved in about half the volume of water” is explicit.
Preservatives are dissolved in:
- remaining propylene glycol (Claim 12)
- a small volume of water (Claim 13)
PVP addition is specifically after suspending agent in Claims 14–15.

Design-around patterns based on this claim language

Changing mixing order (for example, adding buffer fully before wetting drug, or adding suspending agent before pH adjustment) can break literal infringement of the method claims, though composition claims could still be implicated.
Altering preservative solubilization medium could break literal reading of the batch step claims.
Removing or relocating PVP addition could avoid Claims 14–15 but not necessarily Claim 19 if PVP is still present in the finished product.

What patent estate surrounds U.S. Patent 8,057,811 for clozapine oral suspensions in the US?

Answer: The claim focus aligns with a likely cluster of related patent types around clozapine suspension: excipient-stabilized liquid formulations, buffer/pH stabilization, suspending agent selection, preservative systems, and process methods for making such suspensions. However, without the publication number, filing dates, and prosecution history tied to 8,057,811 in your input, a complete US “landscape” mapping (other US patents, assignees, and expiration schedules) cannot be generated from the provided information alone.

Scope anchor for landscape mapping

Formulation theme: physicochemically stable buffered clozapine suspension with wetting + stabilizer + parabens and optionally PVP.
Likely adjacent claim families:
- alternative stabilizers (within xanthan/guar/tragacanth/HPMC/MCC list or close substitutes)
- alternative buffers that keep pH within 6–11
- preservative system variations within parabens
- process mixing-step patents tied to pH adjustment and thickening behavior

When does U.S. Patent 8,057,811 lose exclusivity and how does that affect generic entry risk?

Answer: This requires the patent’s filing date and statutory regime to compute expiration (and any patent term adjustment). Those data are not included in the prompt, so a valid exclusivity timeline cannot be produced from the provided input.

Is U.S. Patent 8,057,811 more about drug product protection or manufacturing process protection?

Answer: It covers both, with stronger product-coverage impact through Claim 1 and Claim 19, and more process-specific narrowing through Claim 12–15.

Product coverage (broader)

Claim 1 is a wide formulation claim because it does not constrain manufacturing steps.
Claim 19 adds the specific presence of PVP plus the same pH and buffer concept.

Process coverage (narrower)

Claim 12–15 provide specific step sequencing, making them comparatively easier to design around for manufacturing unless the finished product still meets the composition claims.

How do the explicit examples in Claims 8 and 17 affect enforcement strategy?

Answer: Claims 8 and 17 are formulation embodiments that can be used as “clean targets” for infringement and validity support if accused products match the listed ingredient set.

Example sets

Claim 8: clozapine + glycerine + sodium dihydrogen phosphate dihydrate/NaOH buffer + xanthan gum + methyl paraben + propyl paraben + water
Claim 17: clozapine + glycerin + sodium dihydrogen phosphate dihydrate/NaOH buffer + xanthan gum + sodium methyl paraben + sodium propyl paraben + water

These embodiments are often persuasive in litigation because they reduce interpretive ambiguity about what ingredient combinations satisfy the claim.

Key claim matrix for assessing an accused clozapine suspension (literal infringement checklist)

Claim element	Literal requirements	In-scope if product matches
Clozapine suspension	clozapine in suspension, aqueous, oral	Yes if liquid suspension form
Wetting agent	one or more of propylene glycol, glycerin, polyethylene glycol	Yes if uses any of these
Stabilizer/suspending agent	one or more of xanthan gum, guar gum, tragacanth gum, HPMC, microcrystalline cellulose	Yes if uses any listed polymer/cellulose
Buffer + pH	pH maintained about 6–11 (Claim 1) and optionally narrowed to 6–8 (Claim 3)	Yes if stability maintained in stated window
Clozapine wt%	about 0.1–10% (Claim 4)	Trigger depends on label strength/concentration
Wetting agent wt%	about 0.1–15% (Claim 5)	Trigger depends on formulation
Preservative	methyl/propyl/butyl parabens (Claim 7)	Yes if any paraben in list
PVP	optional in Claim 1/6 but explicit in Claim 19	Yes for Claim 19 exposure
Stability duration	at least 14 months (Claim 18)	Evidence-driven, may depend on testing conditions
Process steps	specific batch order and allocations (Claims 12–15)	Typically product-related but step sequence matters

Key Takeaways

U.S. Patent 8,057,811 is built around a buffered, wetting-agent-containing aqueous clozapine suspension with explicit coverage of (i) listed wetting agents, (ii) listed stabilizer polymers/cellulose, (iii) pH maintained ~6–11, and (iv) optional parabens and PVP.
Claim 1 provides the broadest product scope; Claim 19 adds explicit PVP presence exposure.
Process claims (12–15) are comparatively narrower because they recite batch sequence and solubilization/volume allocation details tied to achieving pH and thickening behavior.
The enforceability and infringement analysis in practice should focus on whether an accused product uses (a) any of the claimed wetting agents and stabilizers, (b) a buffer that maintains pH within 6–11 (and potentially 6–8), and (c) whether parabens and/or PVP are present.

FAQs

What excipients design around U.S. Patent 8,057,811 while keeping clozapine suspension stability?
Does adding a different buffer system than sodium phosphate/NaOH avoid all claims or only Claim 2?
If a generic uses the same pH and polymers but different mixing order, which claim types remain most relevant?
How does inclusion of PVP change infringement risk under Claim 19 versus Claim 1?
If a product matches the ingredient list but fails the “14 months” stability benchmark, which claim elements become contested?

References (APA)

No citable sources were provided in the prompt, and no publication number, assignee, filing date, or Orange Book listing details are included to support accurate citation.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Douglas Pharms	VERSACLOZ	clozapine	SUSPENSION;ORAL	203479-001	Feb 6, 2013		RX	Yes	Yes	8,057,811	⤷ Start Trial	Y				⤷ 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

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
New Zealand	527142	Jul 23, 2003

PCT Information
PCT Filed	July 22, 2004	PCT Application Number:	PCT/NZ2004/000158
PCT Publication Date:	January 27, 2005	PCT Publication Number:	WO2005/007168

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2004257556	⤷ Start Trial
Canada	2532648	⤷ Start Trial
European Patent Office	1646393	⤷ Start Trial
Spain	2436213	⤷ Start Trial
New Zealand	527142	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,057,811

Which drugs does patent 8,057,811 protect, and when does it expire?

Summary for Patent: 8,057,811