Details for Patent: 7,902,206

Summary for Patent: 7,902,206

Title:	Polymorphic forms α, β and γ of rifaximin
Abstract:	Crystalline polymorphous forms of rifaximin (INN) antibiotic named rifaximin α and rifaximin β, and a poorly crystalline form named rifaximin γ, useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization carried out by hot-dissolving the raw rifaximin in ethyl alcohol and by causing the crystallization of the product by addition of water at a determinate temperature and for a determinate period of time, followed by a drying carried out under controlled conditions until reaching a settled water content in the end product, are the object of the invention.
Inventor(s):	Giuseppe Claudio Viscomi, Manuela Campana, Dario Braga, Donatella Confortini, Vincenzo Cannata, Paolo Righi, Goffredo Rosini
Assignee:	Alfasigma SpA
Application Number:	US12/119,600
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,902,206
Patent Claim Types: see list of patent claims	Composition; Compound; Process; Dosage form;

US Patent 7,902,206 (Rifaximin Polymorph α/β/γ): Scope, Claim Coverage, and US Patent Landscape

US 7,902,206 claims rifaximin polymorphs defined by X-ray powder diffraction (XRPD) peak positions and controlled water content, plus process routes that generate or interconvert polymorphs by water-content control, and solid oral dosage compositions formulated with the specified polymorphic forms. The patent estate is structurally built around three claim “pillars”: (1) substance-by-form polymorph identity (α, β, γ), (2) process-by-parameters for polymorph selection and conversion (water absorption/release control during crystallization or post-treatment), and (3) formulation-by-polymorph, including specific excipient classes and oral dosage form types.

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What does US 7,902,206 claim about rifaximin polymorph Form α, β, and γ?

Core answer: The patent defines rifaximin Forms α, β, and γ by XRPD peak sets plus water content limits, and it prohibits products that are “not derived” from the specified polymorph via water absorption or release.

Claim 1: Form α as a defined XRPD plus “not derived” constraint

Form α XRPD peaks: about 7.4°; 19.7°; 21.0°; 22.1° (2-θ)
Identity constraint: “polymorphic form α free from other polymorphic forms … not derived from Form α by water absorption or release.”

That “free from other polymorphic forms” language tightens the claim from “predominantly α” to “no other forms present,” and the “not derived” limitation adds a provenance test tied to whether the starting material was transformed by water absorption/release.

Claims 2, 3, 9: Form α water-content limits

• Claim 2: water content 3.0%
• Claim 3: water content 4.5%
• Claim 9: water content between 3.0%–4.5%

These dependent claims create enforceable sub-ranges that can be targeted in infringement arguments using Karl Fischer or equivalent water-content assays.

Claim 4: Form β XRPD plus “not derived” constraint

Form β XRPD peaks: about 5.4°; 9.0°; 20.9° (2-θ)
Identity constraint: “polymorphic form β free from other polymorphic forms … not derived from Form β by water absorption or release.”

Claims 5, 10: Form β water-content limits

• Claim 5: water content 5.0%
• Claim 10: water content between 4.5%–5.0%

Claim 6: Form γ XRPD plus “not derived” constraint

Form γ XRPD peaks: about 5.0°; 7.1°; 8.4° (2-θ)
Identity constraint: “polymorphic form γ free from other polymorphic forms … not derived from Form γ by water absorption or release.”

Claims 7, 8, 11: Form γ water-content limits

• Claim 7: water content 0%
• Claim 8: water content 1%
• Claim 11: water content between 0%–1%

Claim 12: Process-defined polymorph “obtained by crystallizing… controlling water content”

Core concept: Even if the product is not produced by the exact conversion steps of later claims, the patent captures polymorph production where the polymorph is obtained by crystallizing rifaximin from a solvent and selecting the polymorph by controlling:

• water content of the polymorph,
• crystallization temperature,
• length of crystallization time.

Claim 12 then repeats the XRPD peak sets for α, β, or γ and ties them to the controlled water-content selection.

Claims 13–17: Interconversion by decreasing or increasing water content

These claims define bidirectional transformation:

• Claim 13: Form β → Form α via decreasing water content “sufficient to convert”
• Claim 14: Form α → Form β via increasing water content “sufficient to convert”
• Claims 15–17: product-by-process wrappers selecting the resulting form (α or β or γ)

Claims 18–19: Conversion of specific XRPD-identified forms by water-content adjustment

• Claim 18: Form β (given XRPD peaks) transformed to Form α (given XRPD peaks) by reducing water content
• Claim 19: Form α transformed to Form β by increasing water content

These claims are narrower than Claim 13/14 by tying both starting and ending polymorph identities to explicit XRPD peak sets.

Technical note for infringement mapping: Because the claims rely on XRPD peak positions and water content, the patent is unusually “analytical” for a pharmaceutical polymorph patent. Claim scope will often turn on whether accused rifaximin meets the specific peak set and whether it falls within the precise water-content range, not just on whether it is “a polymorph.”

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Which formulations are protected by US 7,902,206 for rifaximin solid oral dosage?

Core answer: The patent covers solid pharmaceutical compositions where rifaximin is in polymorphic Form α, β, or γ with the same XRPD peak sets, and where the formulation is oral and made with specified excipient categories.

Claim 20: Solid composition with Form α

• Composition: solid + rifaximin in Form α
• Form α XRPD peaks: 7.4°; 19.7°; 21.0°; 22.1°
• Plus pharmaceutically acceptable excipient/carrier

Claim 21–22: Form α water constraints in the composition

• Claim 21: Form α water content < 4.5%
• Claim 22: water content 2.0%–3.0%

These are tighter than claim 1’s 3.0% and 4.5% endpoints because they introduce both upper and range limitations in composition context.

Claim 23: Excipients as a selected list

Excipients are defined by functional categories: diluting agent, binding agent, lubricating agent, disintegrating agent, coloring agent, flavoring agent, sweetening agent.

Claim 24: Oral dosage forms list

Oral solid dosage forms include:

• coated or uncoated tablets
• hard or soft gelatin capsules
• sugar-coated pills
• lozenges
• wafer sheets
• pellets
• powders in sealed packet

Claims 25–31: Example excipient add-ons

These claims add optional excipients:

• colloidal silicon dioxide (25)
• hydroxypropyl methylcellulose (26)
• cellulose (27)
• microcrystalline cellulose (28)
• propylene glycol (29)
• sodium starch glycolate (30)
• talc (31)

Claim 32–33: Multi-polymorph composition add-ons

• Claim 32: includes Form β as additional polymorph
• Claim 33: includes Form γ as additional polymorph

This matters: it suggests compositions may include multiple polymorphs as long as the primary Form α condition remains satisfied (and the additional forms meet their own XRPD definitions in the dependent claims).

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Does US 7,902,206 cover Form β or Form γ compositions as separate claim “islands”?

Core answer: Yes. The patent contains parallel composition families for Form β (Claims 34–46) and Form γ (Claims 47–57), with distinct XRPD and water-content ranges.

Form β compositions: Claims 34–46

• Claim 34: solid pharmaceutical composition with rifaximin Form β and Form β XRPD peaks: 5.4°; 9.0°; 20.9°
• Claim 35: Form β water content ≥ 4.5%
• Claim 36: Form β water content 4.5%–40%
• Claim 37: excipient category list (same functional categories as claim 23)
• Claim 38: oral dosage forms list (same as claim 24)
• Claims 39–45: optional excipient add-ons identical in structure to α claims (colloidal silicon dioxide, hydroxypropyl methylcellulose, cellulose, microcrystalline cellulose, propylene glycol, sodium starch glycolate, talc)
• Claim 46: composition further comprises Form γ with specified XRPD peaks (5.0°; 7.1°; 8.4°)

Form γ compositions: Claims 47–57

• Claim 47: solid pharmaceutical composition with rifaximin Form γ and Form γ XRPD peaks: 5.0°; 7.1°; 8.4°
• Claim 48: water content 0%–2%
• Claim 49: excipient category list
• Claim 50: oral dosage forms list
• Claims 51–56: optional excipient add-ons (colloidal silicon dioxide, hydroxypropyl methylcellulose, cellulose, microcrystalline cellulose, propylene glycol, sodium starch glycolate)
• Claim 57: talc

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How broad are the claims: what is actually required for infringement?

A. Substantive product elements

To infringe substance claims (e.g., Claim 1, 4, 6), an accused rifaximin must satisfy:

1. Polymorphic identity via XRPD peak sets (specific 2-θ values).
2. Purity/prohibition on other polymorphs (“free from other polymorphic forms”).
3. Water-content (for dependent claim targets; core claim 1/4/6 still defines form without explicit water number).
4. Provenance limitation (“not derived … by water absorption or release”) for the base claims.

B. Dosage form and excipient elements

For composition claims (e.g., Claim 20, 34, 47), infringement additionally requires:

• the product is a solid formulation intended for oral use (depending on the specific dependent claim), and
• excipients fit the specified categories or listed examples.

C. Process claims: parameter-driven

Process scope hinges on:

• crystallizing from a solvent with controlled water content, temperature, and time (Claim 12),
• and/or water-content increasing/decreasing sufficient to convert between specific XRPD-defined polymorphs (Claims 13–14, 18–19).

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What is the practical litigation and “Paragraph IV risk” profile created by this claim structure?

Core answer: The claim architecture favors infringement theories that are achievable through comparative analytics (XRPD + water content) and through manufacturing provenance evidence (whether accused material is “derived” by water absorption/release) and process records (crystallization conditions, water control, interconversion steps).

Typical infringement proof paths suggested by the claim text

• Analytics: Obtain commercial samples and test XRPD and water content. Match peak sets and water ranges to dependent claims.
• Provenance and conversion: Use discovery, batch records, or supplier qualification evidence to show whether accused Form α/β/γ was made by water absorption/release steps, which could trigger the “not derived” limitations as a defense or as a counterpoint depending on the evidence posture.
• Process controls: For process claims, demonstrate crystallization from solvent with controlled water content and crystallization parameters, or show specific water-content adjustments that convert one polymorph to another.

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How many distinct claim “targets” are there for competitors trying to launch rifaximin generics or reformulations?

Core answer: US 7,902,206 creates at least three substance targets (α, β, γ), multiple water-content target variants per form, multiple composition targets per form, and multiple conversion/process targets.

Distinct target clusters by form

Form α

• XRPD: 7.4; 19.7; 21.0; 22.1
• Water-content targets: 3.0%; 4.5%; 3.0–4.5% (substance dependent) and composition water constraints (<4.5%; 2.0–3.0%)
• Process targets: β→α via decreasing water; process-defined crystallization selection

Form β

• XRPD: 5.4; 9.0; 20.9
• Water-content targets: 5.0%; 4.5–5.0% (substance dependent) and composition constraints (≥4.5%; 4.5–40%)
• Process targets: α→β via increasing water; process-defined crystallization selection

Form γ

• XRPD: 5.0; 7.1; 8.4
• Water-content targets: 0%; 1%; 0–1% (substance dependent) and composition constraints (0–2% water)
• Process targets: form γ selection through crystallization parameter control; interconversion wrapper claims

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What does this imply for a generic launch strategy: can competitors “design around” by picking other polymorphs or water levels?

Core answer: The patent makes “design around” possible by moving outside the XRPD peak sets or water-content constraints, but it also makes “design around by interconversion” risky because conversion-by-water control is explicitly claimed.

Likely design-around vectors consistent with the claim language

• Pick a different polymorph not matching α/β/γ peak sets.
• Shift water content outside the dependent claim ranges.
• Use a manufacturing route that avoids being “derived … by water absorption or release,” if that provenance limitation is treated as a strict product attribute.
• Avoid matching the explicit XRPD peak sets by ensuring different polymorphic character.

Counter-risk

Because the claims include process-by-parameters and water-content conversion (Claims 12, 13–14, 18–19), a manufacturer that controls water content during crystallization or uses water absorption/release as a step could collide with process coverage even if final composition meets some excipient variations.

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How does US 7,902,206 compare conceptually with typical polymorph patents in US practice?

Core answer: It is more granular than many polymorph patents because it combines:

• analytical identity markers (XRPD peak lists),
• water-content numerical limitations,
• “free from other polymorphs,” and
• explicit “not derived” provenance constraints, plus it extends to composition embodiments with oral dosage form and excipient category limitations.

This combination tends to raise the evidentiary bar for both sides in litigation but also sharpens infringement maps once accused material is tested.

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Key takeaways

• US 7,902,206 protects rifaximin polymorph identity (α, β, γ) defined by specific XRPD peak sets plus water-content limits in dependent claims.
• The patent also claims processes that obtain or interconvert polymorphs by crystallization parameter control and by water-content increase/decrease sufficient to convert between XRPD-defined forms.
• It covers solid oral compositions where the active ingredient is in the claimed polymorph form and includes excipient-category and oral dosage-form lists, with examples such as colloidal silicon dioxide, HPMC, microcrystalline cellulose, propylene glycol, sodium starch glycolate, and talc.
• The claim design creates multiple infringement “hooks” for generic and reformulation challengers: product testing (XRPD and water), and process/provenance evidence tied to water absorption/release and water-control crystallization steps.

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FAQs

1) Can a product avoid infringement by using the same XRPD peaks but different water content?
Designing outside the dependent water-content ranges (Claims 2–3, 5, 7–8, 9–11; and composition ranges like Claims 21–22, 35–36, 48) can be a key vector because the dependent claims tie infringement to specific water levels.

2) If a manufacturer forms α by converting β through water control, which claims are directly implicated?
Claims 13 and 18 map directly to β→α conversion by decreasing water content sufficient to convert between explicit XRPD-defined forms.

3) Does the patent require “absence” of other polymorphs or is “majority” enough?
The claims use “free from other polymorphic forms,” which reads as a purity requirement rather than a predominance threshold.

4) Are formulation-only changes (different excipients) enough to design around?
Not if the formulation claims are asserted, because the patent covers compositions with rifaximin in the specified polymorphic form and includes broad excipient categories and common excipient examples.

5) Does the patent cover process selection during crystallization from solvent?
Yes. Claim 12 captures crystallization-based polymorph selection by controlling water content, crystallization temperature, and crystallization time.

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References

1. US Patent 7,902,206, “Rifaximin Polymorphs and Methods of Preparation,” claims text as provided by user.

Drugs Protected by US Patent 7,902,206

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 7,902,206

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Italy	M12003A002144	Nov 07, 2003

International Family Members for US Patent 7,902,206

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	043547
Argentina	081991
Argentina	081992
Austria	361927