Scope and Claims of US Patent 9,192,576 (Bromocriptine Mesylate Oral Tablet)

US Patent 9,192,576 is directed to oral solid dosage forms of bromocriptine mesylate, with tightly constrained performance parameters tied to (i) particle size distribution, (ii) dissolution in simulated gastric fluid conditions, (iii) implied gastric/intestinal mucosal absorption, and in some claims (iv) pharmacokinetic timing (Tmax) for bromocriptine under fasting vs high-fat fed conditions. It also includes composition, use (improving glycemic control in type 2 diabetes), and manufacturing process claims focused on producing a defined micronized particle distribution and then blending and compressing into tablets.

The claim set is structurally built around three “design levers” that repeatedly appear across independent and dependent claims:

Micronization / particle size distribution (Dv90 thresholds, span thresholds, and a small-particle cap).
Dissolution release kinetics in 0.1 N HCl at 37°C using USP <711> Apparatus 2 (paddle) at 50 rpm (release percentages at 7, 10, 20, and 30 minutes).
In vivo performance proxies (absorption through gastric and/or intestinal mucosa; Tmax windows for fasting vs fed).

The net effect is an estate that is not limited to “bromocriptine mesylate tablets” broadly. It is limited to tablets that meet a specific physical particle distribution and a specific dissolution release profile in a specific test method and conditions.

What does claim 1 of US 9,192,576 cover in plain claim-scope terms?

Claim 1 is the first core composition claim. It requires all of the following elements:

1) Dosage form type

“Oral tablet” dosage form.

2) Active ingredient and strength

Bromocriptine mesylate in an amount that provides a dose of at least about 0.8 mg of bromocriptine per tablet.

3) Absorption mechanism language

Tablet provides for absorption of a “substantial amount” of bromocriptine “through the gastric and/or intestinal mucosa” when administered.

4) Particle size distribution parameter

Bromocriptine mesylate has a particle size distribution with a span of about 2 or lower.

5) Dissolution release specification

In USP Apparatus Type 2 paddle at 50 rpm, in 500 mL of 0.1 N HCl at 37°C:
- At least about 80% released at about 30 minutes.

Key scope implication

Any product that uses bromocriptine mesylate but does not meet both:

span ≤ ~2, and
≥80% release by ~30 minutes in the specified dissolution test,
falls outside claim 1, even if it has micronized bromocriptine and a similar mg strength.

How do the dependent particle-size claims narrow eligibility?

Multiple dependent claims add hard numeric particle-size cutoffs layered onto claim 1 (or on later independent claim families). The numeric parameters include Dv90 and an “ultrafine fraction” cap.

Dv90 thresholds

Claim 2: Dv90 < ~10 µm.
Claim 4: Dv90 < ~20 µm.
Claim 46: Dv90 about 15 µm or lower.
Claim 47: Dv90 < ~10 µm (within claim 46 dependency).
Claim 50: Dv99 < ~15 µm (within claim 50 dependency).

These are not interchangeable. A formulation with Dv90 of, for example, 14 µm may meet claim 46 (Dv90 ≤ 15 µm) but not claim 2 (Dv90 < 10 µm).

Ultrafine cap

Claim 5: volume-based distribution where not more than ~20% of particles are < ~1 µm.
Claim 21: similar cap applied to a “tablet” claim dependent chain.
Claim 26: explicitly limits not more than about 20% < ~1 µm alongside additional dissolution limits.

The inclusion of this cap targets formulations that achieve speed via extreme fine grinding that increases ultrafines. Even if dissolution improves, a higher ultrafine fraction can move the product outside the claim.

Span requirement repetition

“Span about 2 or lower” appears in multiple places:
- Claim 1 (span ≤ 2)
- Claim 5 (paired with ultafine cap)
- Claim 22
- Claim 30 (explicit Dv90 < 10 µm + span ≤ 2)
- Claim 48 (span ≤ 2 within claim 46 chain)

This creates a “shape” constraint on the distribution beyond just Dv90.

What dissolution profile limitations protect in vitro release performance?

Dissolution limitations are written as discrete acceptance windows at specific timepoints using a single test protocol.

Core dissolution baseline

Claim 1: ≥80% released at ~30 min (USP 2 paddle, 50 rpm, 500 mL 0.1 N HCl, 37°C).

Higher early-to-mid dissolution

Claim 3: ≥90% at ~30 min.
Claim 6: ≥90% at ~20 min.
Claim 7: at ~7 min, ≥50% released, and at ~10 min, not more than 75% released (a constrained window).

Tighter “release-at-early timepoints” performance

Claim 24 (dependent on claim 16):
- at ~7 min: not more than ~50% released
- at ~10 min: not more than ~75% released
  This one is notable because it caps early release, which is inconsistent with a naive “faster is always better” formulation approach. It defines an early-release ceiling rather than a floor.

Additional “fast by 30 min” plus early cap

Claim 26 combines multiple dissolution constraints:
- at ~7 min: ≤ ~50%
- at ~10 min: ≤ ~75%
- at ~30 min: ≥ ~80%

Dissolution tests recur in manufacturing and use claims

The same dissolution method appears:

in tablet composition claims,
in method-of-manufacture claims (claims 34 and 38),
and in therapeutic method claims (claims 37, 41, 43, 45, 49, 54).

What about pharmacokinetic (Tmax) restrictions does US 9,192,576 impose?

Tmax limitations appear in composition claim 8, and then in dependent claims tied to claim 1 and later micronized embodiments.

Claim 8 (pharmacokinetic profile)

Requires:

All elements of claim 1 (tablet, dose ≥0.8 mg bromocriptine, absorption through gastric/intestinal mucosa, span ≤2, dissolution release ≥80% at ~30 min)
plus Tmax windows:
- Fasting: Tmax between ~30 and ~60 min, or
- High-fat fed: Tmax between ~90 and ~120 min.

Claim 25 and claim 52

Both repeat the same pharmacokinetic timing windows within dependent structures.

Additional morning administration linkage

Claims 44 and 54 incorporate:

“administered in the morning within about two hours after waking”
plus composition constraints including the Tmax timing and/or dissolution.

This matters for enforcement because it creates method-of-use specificity: even if a tablet has the same dissolution and particle specs, a time-of-day dosing regimen may fall outside a method claim that requires morning-within-2-hours administration.

What therapeutic use do the claims cover (and how is it constrained)?

Method claims for type 2 diabetes glycemic control

Claim 10: administering an oral dosage form according to claim 1 to improve glycemic control in a type 2 diabetes patient.
Claim 14: similarly, according to claim 8 (includes Tmax).
Claims 27, 31, 34, 39, 42, 43, 44, 45, 53, 54: multiple parallel method claims tied to different dependent composition claim families.

Timing of administration

Claim 13/15/28/32/36/40/42/44/45/48/54 (as applicable to the dependent chain) include:
- tablet administered in the morning within about two hours after waking.

Scope implication

The estate supports both:

composition infringement theories (product is made/sold with the claimed specs), and
method infringement theories (how it is administered in a dosing regimen, and potentially under fasting vs fed conditions if the claim requires Tmax).

What manufacturing/process claims exist, and what do they require?

US 9,192,576 contains process claims that can be used to attack production routes even where product form is otherwise similar.

Claim 34: method for manufacture

Requires:

Processing bromocriptine mesylate to reduce average particle size to:
- Dv90 < ~10 µm
- and not more than ~20% < ~1 µm after processing
Blending processed bromocriptine mesylate with excipients so bromocriptine is “substantially evenly distributed”
Compressing mixture to form a tablet
Tablet produced must meet:
- dose ≥ ~0.8 mg bromocriptine per tablet
- dissolution: ≥80% released at ~30 min (USP 2 paddle conditions defined)

Claim 38: method via “determining” particle-size distribution

Claim 38 is a variation that shifts emphasis:

determining bromocriptine mesylate has an equivalent particle size distribution meeting:
- Dv90 < ~10 µm
- not more than ~20% < ~1 µm
then blending and compressing under the same dissolution performance requirements.

Claim 35 and 39: treatment via preparation

These tie manufacturing to patient treatment:

preparing at least one tablet by the process claim
providing tablet for oral administration for glycemic control
and then include the “morning within two hours after waking” and dissolution refinements through dependent layers.

How broad is the claim estate across bromocriptine particle-size and dissolution design space?

The claims create at least three overlapping “clusters” of product eligibility:

Cluster A: claim 1 baseline

span ≤2
≥80% release at 30 min
dose ≥0.8 mg bromocriptine per tablet
absorption language

Cluster B: micronized and tighter dissolution/PK

Dv90 thresholds (often <10 µm)
optional ultrafine caps (<1 µm fraction ≤20%)
multiple dissolution targets:
- ≥90% by 30 min, or ≥90% by 20 min
- or early release windows with early caps at 7 and 10 min
optional Tmax windows (fasted 30-60 min; fed 90-120 min)

Cluster C: alternative Dv90 ceiling embodiment (claim 46 family)

Dv90 ≤ about 15 µm
plus ≥80% release at 30 min
and optionally Dv90 <10 µm (claim 47), span ≤2 (claim 48), and PK constraints (claim 52)

This cluster structure means a competitor can avoid one set by failing a specific particle or dissolution parameter, but may still overlap with another cluster if only one metric differs.

Where are the highest-risk “design-around” choke points?

The claims most strongly constrain:

Dissolution testing conditions and acceptance thresholds
- Same apparatus, rpm, fluid volume, acid normality, and temperature.
- A product that meets in another medium or with different agitation may avoid literal infringement.
Particle distribution “span” and ultrafine fraction
- Span ≤2 is a distinct descriptor that is not reducible to a single Dv90 number.
- The “not more than 20% < 1 µm” cap is a second independent descriptor that blocks aggressive ultrafine milling strategies.
Tmax windows
- Where claimed (not in every independent claim), the PK requirement creates an in vivo performance barrier that is hard to prove without bridging studies.
Morning administration within two hours
- For method-of-use claims that include this requirement, time-of-day dosing is a potential non-infringement lever.

What would a hypothetical generic or follow-on tablet need to match or avoid? (Claim-by-claim infringement logic)

If the product matches claim 1 elements

A follow-on oral tablet with bromocriptine mesylate at ≥0.8 mg, span ≤2, and ≥80% dissolution by 30 minutes in the defined USP test would be within the claim 1 baseline even if other attributes differ (unless dependent claims also required).

To avoid broader capture

A product can attempt to avoid at least one required element in each relevant claim family:

Use a particle distribution with span >2 and/or Dv90 above specific cutoffs where those dependent claims are asserted.
Adjust processing so that the fraction <1 µm exceeds 20% (to avoid claims with the ultrafine cap) while maintaining or changing dissolution behavior.
Change dissolution behavior so that release at a specific timepoint fails (for example, fail the ≥90% at 20 minutes claim 6, or fail the “≤50% at 7 minutes” constraints in claim 24/26 families).
Where Tmax is required, shift exposure timing outside the claimed windows through formulation changes or food effects.

Key structured claim matrix (what must be true simultaneously?)

Composition/Product constraints

Parameter	Claim 1	Claim 2	Claim 3	Claim 6	Claim 7	Claim 8
Dosage form	Oral tablet	Oral tablet	Oral tablet	Oral tablet	Oral tablet	Oral tablet
Dose	≥0.8 mg bromocriptine/tablet	same	same	same	same	same
Particle descriptor	Span ≤2	Dv90 <10 µm	same	same	same	Span ≤2
Dv90	not required	<10 µm	not required	not required	not required	not required (span required)
Ultrafines <1 µm	not required	not required	not required	not required	not required	not required
Dissolution test	USP 2, 0.1N HCl, 37°C, 50 rpm	same	≥90% @30 min	≥90% @20 min	≥50% @7 min; ≤75% @10 min	≥80% @30 min
PK (Tmax)	no	no	no	no	no	yes (fast: 30-60; fed: 90-120)

This shows how claim coverage tightens. The baseline claim is dissolution + span + absorption + dose. Dependent claims add Dv90, higher dissolution, early-time window constraints, and PK.

How should enforcement and freedom-to-operate be evaluated within this patent scope?

Product-level infringement is dominated by literal parameter matching:
- particle distribution descriptors (span, Dv90/Dv99, ultrafines <1 µm),
- dissolution acceptance criteria,
- and sometimes PK windows.
Method-of-use infringement depends on:
- the underlying composition (must still meet the claim-linked parameters),
- plus patient population (type 2 diabetes),
- and potentially administration timing (“morning within about two hours after waking”).

Manufacturing method claims provide a secondary litigation path: even if a defendant argues product equivalence, process claims target specific processing objectives (achieving Dv90 <10 µm and limiting ultrafines).

Key Takeaways

US 9,192,576 claims bromocriptine mesylate oral tablets with a defined particle size distribution (span ≤ ~2; and in many dependents Dv90 <10 µm and/or ultafines <1 µm ≤20%) plus a defined dissolution release profile in USP Apparatus 2 conditions (0.1 N HCl, 37°C, 50 rpm).
The most enforceable choke points are span, ultrafine fraction, and timepoint-specific dissolution limits (especially the combinations at ~7, ~10, ~20, and ~30 minutes).
Where present, Tmax windows (fasting 30-60 min; high-fat fed 90-120 min) add a high practical barrier to design-arounds.
Method claims add type 2 diabetes glycemic control and sometimes a morning dosing window (within about two hours after waking), enabling time-of-administration-based non-infringement arguments.

FAQs

What parts of US 9,192,576 can be avoided by changing dissolution media or apparatus settings?
Only claims that recite the specific USP Apparatus Type 2 paddle method with the defined conditions (0.1 N HCl, 500 mL, 50 rpm, 37°C) constrain literal scope.
Does US 9,192,576 require Dv90 in claim 1?
No. Claim 1 requires span ≤ ~2 and the dissolution acceptance threshold; Dv90 is introduced in dependent claims.
How do the “≤50% at 7 minutes” and “≤75% at 10 minutes” constraints change formulation strategy?
They cap early release, so “more dissolution earlier” can become non-compliant if it exceeds those ceilings, even if final release at 30 minutes remains high.
Are manufacturing process claims tied to in vivo pharmacokinetics?
The manufacturing claims focus on achieving specific particle size distribution targets and producing a tablet meeting the specified dissolution profile. PK is not the manufacturing-process requirement.
Can a generic avoid method claim exposure by changing dosing time of day?
For method claims that include “morning within about two hours after waking,” changing administration timing can avoid literal satisfaction of that element, assuming the product otherwise meets or fails other claim-linked parameters as required.

References

US Patent 9,192,576 (claims provided in prompt).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Veroscience	CYCLOSET	bromocriptine mesylate	TABLET;ORAL	020866-001	May 5, 2009		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y			IMPROVEMENT OF GLYCEMIC CONTROL IN INDIVIDUALS WITH TYPE 2 DIABETES	⤷ 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
Argentina	091351	⤷ Start Trial
Australia	2013256558	⤷ Start Trial
Australia	2016202572	⤷ Start Trial
Australia	2018203021	⤷ Start Trial
Brazil	112014027087	⤷ Start Trial
Canada	2872300	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,192,576