Details for Patent: RE47301

Which drugs does patent RE47301 protect, and when does it expire?

Patent RE47301 protects LEXISCAN and is included in one NDA.

This patent has twenty-eight patent family members in eighteen countries.

Summary for Patent: RE47301

Title:	Process for preparing an A2A-adenosine receptor agonist and its polymorphs
Abstract:	Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.
Inventor(s):	Jeff Zablocki, Elfatih Elzein, Robert Seemayer, Travis Lemons
Assignee:	Gilead Sciences Inc
Application Number:	US15/653,860
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE47301
Patent Claim Types: see list of patent claims	Composition; Compound; Process;

Executive summary RE47301 is a reissue patent that, based on the provided claims, is tightly scoped to a specific active ingredient form (a crystalline monohydrate of the named A2A adenosine receptor agonist compound) and to composition/process controls that define that form’s impurities, purity, and X-ray powder diffraction (XRPD) signature. The claim set is not a broad “any crystalline form” estate. It is a “monohydrate with a defined solid-state identity and controlled 2-hydrazinoadenosine impurity” estate, with additional dependent claim layers for (i) exclusion of other hydrates/amorphous forms, (ii) a minimum purity threshold (≥ about 99.6%), and (iii) XRPD peak location constraints (peaks at about 2θ of ~6, 9, 11, 13, 14.5, 16.5, and 18 by Cu-Kα1). Design-around space exists primarily through using different solid-state forms, different impurity profiles, or different crystalline identity characterization that does not meet the asserted XRPD “peak-at” limitations.

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RE47301 patent analysis: What claims cover crystalline monohydrate XRPD, purity, and 2-hydrazinoadenosine controls for an A2A adenosine receptor agonist?

What is RE47301’s practical claim scope from the independent claim language?

Core independent claim concept (Claim 1, per provided text):
A pharmaceutical composition prepared from the named compound in a specific crystalline monohydrate form plus at least one pharmaceutically acceptable carrier.

From that language, the scope is defined by two pillars:

1. Form/solid-state identity: “crystalline monohydrate form of the compound (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide.”
2. Composition context: it is made into a pharmaceutical composition with at least one carrier.

No dosage, route, or specific formulation excipients are stated in the claim text you provided, so the carrier selection is broad. The real narrowing comes from dependent claims that lock in impurity and solid-state purity/identity evidence.

How do dependent claims narrow the scope?

Dependent claims (2–5, 11–15, 4–5 etc.) layer in:

• Impurity exclusion: “substantially free of 2-hydrazinoadenosine” (Claims 2 and 11).
• Solid-state exclusivity: monohydrate “substantially free of other hydrates or amorphous form” (Claims 3 and 12).
• Purity threshold: purity ≥ about 99.6% (Claims 4 and 13).
• XRPD limitation: defined peak set at specific 2θ values measured by Cu-Kα1 (Claims 5 and 14).
• Figure-specific XRPD: claim versions referring to “FIG. 3” (Claims 10 and 15).

What is the process-related coverage?

RE47301 includes a process-style composition claim (Claim 6) that ties infringement risk to a manufacturing step:

• dissolving a crystalline monohydrate form (as defined by being substantially free of 2-hydrazinoadenosine) in a pharmaceutically acceptable carrier.

This does not appear to claim crystallization conditions explicitly (no seeding temperatures, solvent systems, residence times, or humidity controls are present in the text you supplied). Instead, it claims an end-state composition made using a defined form that is defined by its purity/identity characteristics. That means the key evidentiary battle in litigation would likely be:

• Does the accused material qualify as the claimed crystalline monohydrate?
• Is it substantially free of 2-hydrazinoadenosine?
• Does it meet the XRPD peak constraints if those dependent claims are asserted?

How broad is Claim 17 compared with Claims 1–5?

Claim 17 is an explicit concentration statement:

• “99.6% pure” named compound dissolved in a pharmaceutically acceptable carrier.

This claim tightens the “purity” element and still ties to dissolution in carrier. It is narrower than the generic “prepared from” language in Claim 1 because it includes a specific purity wording (99.6%) rather than “at least about 99.6%” depending on interpretation.

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How do the XRPD and purity limitations work as claim boundaries for infringement risk?

Which limitations are likely to be dispositive in practice?

The XRPD and purity thresholds are the most litigation-relevant because they convert a “form” concept into measurable analytical criteria:

• Purity: ≥ about 99.6% (Claims 4 and 13).
• Impurity: substantially free of 2-hydrazinoadenosine (Claims 2 and 11).
• XRPD: peaks around specified 2θ values for Cu-Kα1 (Claims 5 and 14).
• Exclusion of other solid states: “substantially free of other hydrates or amorphous form” (Claims 3 and 12).
• Figure-based XRPD: “as shown in FIG. 3” (Claims 10 and 15).

What is the effective “claim map” of solid-state requirements?

Based on the claim set you supplied, the minimum “high-confidence infringement” set is:

• Use the claimed crystalline monohydrate of the named compound (Claims 1, 6, 11).
• Ensure the solid is substantially free of 2-hydrazinoadenosine (Claims 2, 6, 11).
• If asserted, meet additional narrowing elements:
  • No meaningful other hydrates/amorphous (Claims 3, 7, 12).
  • Purity threshold (Claims 4, 8, 13, 17).
  • XRPD peak list (Claims 5, 9, 14).
  • XRPD pattern matching FIG. 3 (Claims 10, 15).

What does “substantially free” imply operationally for challengers?

The claim text does not quantify “substantially free,” so infringement is likely anchored to whatever analytical threshold the patentee used in prosecution and whatever acceptance criteria the accused manufacturer can show or refute. Still, the inclusion of both “substantially free” and an explicit ≥99.6% purity suggests the patentee intended measurable impurity control and a tightly controlled solid-state form.

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Which other claims appear functionally redundant or overlapping in RE47301’s provided claim set?

Claims 11–15 are largely a mirror of Claims 1–5

• Claim 11 includes the same two-ingredient elements: crystalline monohydrate and carrier, plus “substantially free of 2-hydrazinoadenosine.”
• Claims 12–15 parallel Claims 3–5 and 10 (figure reference), respectively.

Claim 6 overlaps Claim 1 but adds an A2A process framing

Claim 6 explicitly characterizes the composition as an “A2A-adenosine receptor agonist produced by a process comprising” dissolving the defined crystalline monohydrate in carrier.

This can matter in enforcement because it asserts a therapeutic function (A2A receptor agonist) tied to a process step. Still, because the active ingredient is the same defined compound and the step is dissolution, the infringement battle is still expected to pivot on whether the accused material meets the solid-state and impurity constraints.

Claim 10 and Claim 15 add “FIG. 3” narrative constraints

The “X-ray diffraction pattern as shown in FIG. 3” provisions likely act as an alternative method to establish that the XRPD peak constraints are met, depending on claim construction of “as shown” and how strictly courts treat the visual figure vs. the numeric peak list.

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What is the likely patent estate coverage beyond RE47301 for the same molecule and solid-state form?

What this claim set signals about the likely wider landscape

RE47301’s claim architecture is typical of estates that also include:

• earlier patents covering the molecule itself (structure, synthesis, intermediates),
• separate patents covering specific solid-state forms (polymorphs, hydrates, solvates),
• and additional patents on impurity control, purification, and solid-state transformation steps.

Even without additional patent numbers provided here, the claim text itself indicates that at least one earlier patent family member likely claimed:

• the preparation of the crystalline monohydrate, and/or
• the XRPD “fingerprint” and impurity control (2-hydrazinoadenosine).

Where competitors should focus if RE47301 is being asserted

If RE47301 is asserted, competitors generally need to assess:

1. Whether their active pharmaceutical ingredient (API) qualifies as the same crystalline monohydrate.
2. Whether their purification process removes 2-hydrazinoadenosine to a comparable extent.
3. Whether any “other hydrate” or “amorphous” co-content exists that might take the product outside “substantially free of other hydrates or amorphous.”

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How strong is RE47301’s patentability position based on the claim structure provided?

Strength drivers

The claims are anchored to objective, testable characteristics:

• XRPD peak locations for Cu-Kα1,
• explicit minimum purity (about 99.6%),
• explicit impurity identity (2-hydrazinoadenosine),
• and exclusion of other hydrates/amorphous.

Such features tend to withstand broad novelty/obviousness attacks better than “product by result” claims that are not tied to measurable properties, assuming the specification supports the measured characteristics.

Vulnerability drivers

The same objectivity can create invalidity arguments around:

• whether the XRPD peaks are reproducible under ordinary variation (instrument, sample preparation, preferred orientation, humidity history),
• whether prior art solid-state forms overlap sufficiently,
• whether “substantially free” is indefinite or overly functional without clear numerical boundaries.

Still, on the information provided, the strongest reading for the patentee is that the measured XRPD and purity threshold convert the claim into a narrow, form-specific control that is less likely to be anticipated by a generic “hydrate” disclosure.

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What generic entry risks exist under RE47301 for products using the monohydrate API form?

High-risk scenario for generics

A generic that launches with:

• API that is the claimed crystalline monohydrate,
• impurity profile containing sufficiently low 2-hydrazinoadenosine,
• and meets the XRPD peak set at the required 2θ values,

faces direct risk against dependent claims (and potentially independent claim 1) even if the generic formulation otherwise differs.

Lower-risk scenario

Risk drops if a generic can demonstrate at least one of the following:

• the API is not the claimed monohydrate (for example, a different hydrate form or a different crystalline polymorph),
• the API is not “substantially free” of 2-hydrazinoadenosine,
• the product contains meaningful other hydrates/amorphous form (if that dependent limitation is asserted),
• XRPD does not match the required peak list or FIG. 3 pattern.

Why formulation changes may not be enough

Because Claim 1 only requires “a pharmaceutical composition” with at least one carrier, generic formulation excipient swaps do not avoid infringement if the API solid-state identity and impurity controls remain within the claimed envelope.

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How does RE47301 compare with typical solid-state patents: what is the design-around strategy?

Design-around levers implied by the claim limitations

A challenger can target:

1. Solid-state form: move from the crystalline monohydrate to another hydrate, solvate, or amorphous.
2. Impurity strategy: keep 2-hydrazinoadenosine above the “substantially free” concept, if safe for bioequivalence and acceptable for regulatory purposes.
3. Purity endpoint: drop below ≥ about 99.6% (harder because it can be unsafe and also undermines stability).
4. XRPD match failure: ensure the XRPD peak list is not satisfied.

Of these, the cleanest regulatory-aligned design-around is usually a different solid-state form, if it still yields equivalent exposure and stability.

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What is the likely Orange Book status impact of RE47301-type claims?

What would these claims cover on an Orange Book listing?

These claims look like they are intended to cover:

• API that is manufactured and characterized by XRPD/purity,
• plus finished dosage forms that include the composition with carriers.

On an Orange Book listing, a patent like this would typically be tied to:

• the drug product’s active ingredient monohydrate form,
• and possibly to specific dosage forms if the carrier or formulation aspects are tied to approved labeling.

Because the provided claim text does not specify dosage form (tablet, capsule, solution, etc.), Orange Book linkage would depend on how the reference-listed drug (RLD) and manufacturing description were framed in the patent assignment/Orange Book submission.

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Key Takeaways

• RE47301 is a solid-state form-focused estate built around a crystalline monohydrate of a specific A2A adenosine receptor agonist compound plus carrier-based pharmaceutical compositions.
• The claim set narrows infringement risk through objective analytical limitations: “substantially free of 2-hydrazinoadenosine,” ≥ about 99.6% purity, and XRPD peak constraints (Cu-Kα1 peaks at ~2θ 6, 9, 11, 13, 14.5, 16.5, 18) and/or matching FIG. 3.
• A2A framing appears in Claim 6, but the enforceable boundary still centers on the defined monohydrate identity and impurity/purity profile rather than on dosing or specific excipient recipes.
• Generic and biosimilar-style entry risk is primarily driven by whether an accused API is the same monohydrate and whether analytical testing meets the defined impurity/purity/XRPD gates. Formulation changes alone are unlikely to be sufficient to avoid infringement if the API still meets the claimed identity constraints.

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FAQs

1) Can a product avoid RE47301 by using a different hydrate or polymorph of the same compound?

Yes. The dependent claims require the API to be a crystalline monohydrate and, if asserted, “substantially free of other hydrates or amorphous form.” Switching solid-state form is the clearest pathway implied by the claim language.

2) What is the practical importance of “as measured by Cu-Kα1” in the XRPD claims?

It locks the XRPD measurement method to Cu-Kα1, making infringement and non-infringement more testable and reducing arguments based on alternative radiation sources.

3) Does RE47301 require a specific dosage form (tablet, capsule, injection)?

Not in the provided claims. The claims require a pharmaceutical composition with a pharmaceutically acceptable carrier, without tying to a particular finished dosage form.

4) What is the strongest claim limitation for competitors to dispute?

The most litigation-leveraged disputes are typically the XRPD peak set (Claims 5 and 14) and impurity status for 2-hydrazinoadenosine (Claims 2 and 11), because both are analytically defined in the claim set.

5) How do “FIG. 3” XRPD references change the infringement analysis?

They create an additional path to establish the XRPD signature by reference to a disclosed pattern, potentially lowering the need for strict peak-by-peak numerical proof depending on claim construction.

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References

1. RE47301 (provided claim text in user prompt).

Drugs Protected by US Patent RE47301

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astellas	LEXISCAN	regadenoson	SOLUTION;INTRAVENOUS	022161-001	Apr 10, 2008	AP	RX	Yes	Yes			Y

International Family Members for US Patent RE47301

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007212542
Canada	2640089
Canada	2787759
China	101379073
China	102260311
European Patent Office	1989214