Details for Patent: 5,821,236

Summary for Patent: 5,821,236

Title:	Tumor treatment with arabinofuranosyl purine derivatives
Abstract:	6-Alkoxy derivatives of Ara-G, and pharmaceutically acceptable esters thereof, are described as being useful in tumor therapy. Novel pharmaceutically acceptable esters, their preparation and pharmaceutical formulations containing them are also disclosed.
Inventor(s):	Thomas Anthony Krenitsky, Devron Randolph Averett, George Walter Koszalka
Assignee:	Novartis AG , Novartis Pharma AG
Application Number:	US08/449,078
Patent Claim Types: see list of patent claims	Use;

US Patent 5,821,236 Landscape: What the Claims Cover, How Broad the Method-of-Use Scope Is, and Where Generics/Biosimilars Face Patent Barriers

US Patent 5,821,236 (method for inhibition of susceptible tumors by administering a specific substituted purine nucleoside analog with a methoxy (R1) substituent, including multiple protected ribose/arabinofuranosyl forms) is a claims-driven, method-of-use patent focused on anti-tumor administration and specific compound structures. The claim set is narrow-to-medium in practice because it hinges on the compound formula (I) with a defined R1 identity (C1-5 alkoxy or a pharmaceutically acceptable ester/salt of that moiety) and then funnels into a limited set of enumerated exemplified compounds and one explicit compound in dependent claims.

Scope at a glance

• Independent claim (claim 1): method of inhibiting susceptible tumors in a mammal by administering an effective tumor-inhibiting amount of a compound of formula (I) with R1 = C1-5 alkoxy (or its pharmaceutically acceptable ester or salt).
• Dependent claims (claims 2–4): specify methoxy and enumerate specific nucleoside analogs with 2-amino-6-methoxy-9H-purine plus arabinofuranosyl protecting group patterns (acetyl, isobutyryl), and single out one exact compound: 2-amino-6-methoxy-9-(5-O-acetyl-β-D-arabinofuranosyl)-9H-purine (claim 4).

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What does US 5,821,236 claim scope cover for tumor inhibition methods (formula I, R1 alkoxy)?

Direct answer: Claim 1 covers a method-of-treatment (method-of-use) for tumor inhibition in mammals where the treatment is administered as an effective amount of a compound matching formula (I), with R1 defined as a C1-5 alkoxy or an ester/salt thereof.

Claim-1 elements that define infringement risk

Claim 1 is structured as:

1. “A method for inhibition of susceptible tumours in a mammal”
2. “administering … an effective tumour inhibiting amount”
3. “a compound of formula (I)”
4. “wherein R1 is a C1-5 alkoxy group or a pharmaceutically acceptable ester or salt thereof.”

Practically, infringement analysis turns on three technical matches:

• Disease state / biological target: “susceptible tumours” is broad conceptually (any tumor susceptible to the compound’s activity), but it still requires the therapeutic context to be consistent with “tumour inhibition.”
• Species: “a mammal” spans humans plus veterinary species.
• Active structure match: the formula (I) must match including the R1 substitution definition.

How “R1 = C1-5 alkoxy (or ester/salt)” impacts breadth

The R1 term is a classic leeway for formulation and salt/ester derivatives, but the claim still anchors to a specific substitution class:

• R1 limited to alkoxy within C1–C5: that is narrow compared with “any alkoxy.”
• R1 includes pharmaceutically acceptable ester or salt: this broadens to prodrug/derivative forms where the alkoxy moiety is converted to an ester, and to pharmaceutically acceptable salt forms of the compound.

Key consequence for freedom-to-operate: a competitor cannot avoid claim 1 by using a different alkoxy carbon-length beyond C1–C5. They also cannot easily avoid claim 1 by moving to an ester/salt that still preserves the underlying R1 identity in claim language.

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How do dependent claims 2–4 narrow US 5,821,236 (methoxy and enumerated arabinofuranosyl purines)?

Direct answer: Claims 2–4 narrow claim 1 to a methoxy R1 and then further constrain the drug candidate to specific enumerated nucleoside analogs with 2-amino-6-methoxy-9H-purine and arabinofuranosyl sugar protection patterns.

Claim 2: R1 = methoxy

Claim 2 locks R1 to methoxy (a single carbon alkoxy). That matters because:

• A formula (I) compound with ethoxy/propoxy/butoxy/pentoxy could still fall within claim 1, but not claim 2.
• A compound that changes the alkoxy chain length can avoid methoxy-specific dependent claims while still potentially entering claim 1’s coverage.

Claim 3: enumerated compound set (7 members)

Claim 3 is a “select compound” dependency: it restricts claim 1 to compounds selected from the listed set, all built on a shared scaffold:

• 2-amino-6-methoxy-9H-purine
• 9-(β-D-arabinofuranosyl)-9H-purine with O-acyl substitutions at specific positions (2-O, 3-O, 5-O) and one isobutyryl example.

The listed set includes:

1. 9-(3,5-di-O-Acetyl-β-D-arabinofuranosyl)-2-amino-6-methoxy-9H-purine
2. 9-(2,5-di-O-Acetyl-β-D-arabinofuranosyl)-2-amino-6-methoxy-9H-purine
3. 9-(2-O-Acetyl-β-D-arabinofuranosyl)-2-amino-6-methoxy-9H-purine
4. 9-(2,3,5-tri-O-Acetyl-β-D-arabinofuranosyl)-2-amino-6-methoxy-9H-purine
5. 9-(5-O-isobutyryl-β-D-arabinofuranosyl)-2-amino-6-methoxy-9H-purine
6. 9-(2,3-di-O-Acetyl-β-D-arabinofuranosyl)-2-amino-6-methoxy-9H-purine
7. 2-amino-6-methoxy-9-(5-O-acetyl-β-D-arabinofuranosyl)-9H-purine

Key claim-coverage implication: claim 3 does not read on every possible protecting group pattern. It reads on the set enumerated. That makes it a significant practical limiter for competitors making close analogs with different acetyl/isobutyryl placement.

Claim 4: single explicit compound

Claim 4 further restricts to:

• 2-amino-6-methoxy-9-(5-O-acetyl-β-D-arabinofuranosyl)-9H-purine

This is the smallest-scope dependent claim and the easiest for design-around analysis: competitors targeting different O-acyl regiochemistry (for example, 2-O-acetyl rather than 5-O-acetyl) or different sugar protection patterns can avoid claim 4 while remaining potentially exposed to claim 1 or claim 3.

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What compounds are within US 5,821,236 claim scope (mapping the enumerated examples to formula I requirements)?

Direct answer: The enumerated dependent compounds all satisfy the shared structural requirements implied by claim 1’s formula (I): a purine core with 2-amino-6-methoxy-9H-purine substitution and an O-acyl arabinofuranosyl moiety.

Practical “claim chart” logic (structure-to-claim mapping)

A competitor’s compound is inside at least one dependent claim if it satisfies all of:

• Purine core has 2-amino
• Purine core has 6-methoxy
• Nucleoside has β-D-arabinofuranosyl linked at the 9-position
• O-acyl protecting group pattern matches one of the enumerated patterns in claim 3
• The therapeutic use includes tumor inhibition in a mammal by administering an effective amount

What the claims do not expressly cover

Based on the claim text provided:

• No explicit coverage is stated for non-methoxy alkoxy substituents beyond claim 1’s “C1-5 alkoxy” class.
• No explicit coverage is stated for different sugar stereochemistry (for example, alternative anomeric configuration) outside the listed β-D-arabinofuranosyl embodiments, though claim 1 could still cover them if they fall within formula (I) as written.
• No explicit coverage is stated for formulation-specific dosage forms; the claims are method-of-use, so they do not require a particular dosage unit, but they do require administration of the specified compound.

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How strong is the US 5,821,236 patent estate for method-of-use enforcement (formulation-independent vs compound-dependent)?

Direct answer: Strength is driven by compound identity and administration facts. It is a method-of-use claim, so enforcement depends on proving that a defendant administered a covered compound in an effective amount for tumor inhibition in a mammal.

Strength drivers

1. Compound-defined claim anchor
   Claim 1 ties infringement to a compound of formula (I) and a defined R1 class. This is a cleaner target than pure behavioral claims.
2. Methoxy concentration via dependent claims
   Claims 2–4 give additional layers of coverage if the accused compound has methoxy at the purine ring.
3. Enumerated O-acyl patterns
   Claim 3 narrows to specific acyl patterns, which can help litigators argue clear chemical overlap for those variants.

Weakness / friction points

1. Method-of-use proof burden
   For method-of-use patents, accused activity must include the tumor-inhibiting therapeutic use. Generic manufacturing and sale alone may not automatically establish the claimed method absent evidence tied to use instructions and prescribing.
2. Design-around by moving outside R1 methoxy class
   Claim 1’s R1 is limited to C1–C5 alkoxy. Switching to a non-C1–C5 alkoxy (or removing the defined substitution) can reduce exposure, while still needing to maintain anti-tumor activity.
3. Design-around by moving outside enumerated sugar protection patterns
   Claim 3 and 4 give clear boundaries. Changing the acyl regiochemistry can avoid those dependents, leaving only the broad independent claim exposure if the changed compound still fits formula (I).

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What patents typically surround US 5,821,236 in similar nucleoside analog estates (claims you should expect near the same expiry window)?

Direct answer: In nucleoside analog families, close companion IP often includes: (i) synthesis/process claims, (ii) additional compound formula variants (alternative sugar protection or ring substitutions), and (iii) other tumor/indication methods. Without the full family record for 5,821,236, no firm counts or specific adjacent patent numbers can be asserted here.

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When does US 5,821,236 lose exclusivity (what are the practical expiration triggers)?

No complete and accurate exclusivity or expiration timeline can be produced from the claim text alone.

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What is the Orange Book status of US 5,821,236 (and what does it mean for generic entry)?

No complete and accurate Orange Book status can be produced from the claim text alone.

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Which Paragraph IV or §505(b)(2) challenges could implicate this patent (method-of-use and compound coverage)?

No complete and accurate listing of Hatch-Waxman filings or Paragraph IV litigations can be produced from the claim text alone.

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Key takeaways

• US 5,821,236 is a compound-defined, method-of-use patent: infringement requires administration of a covered formula (I) compound to achieve tumor inhibition in a mammal.
• Claim 1 provides broader coverage via R1 = C1–C5 alkoxy (plus ester/salt forms), which is the main lever for attacking or defending scope.
• Claim 2 narrows to methoxy and is a meaningful secondary coverage layer for methoxy-substituted analogs.
• Claim 3 confines coverage for methoxy analogs to an enumerated set of arabinofuranosyl O-acyl patterns, enabling straightforward design-around by altering protecting-group placement outside the list.
• Claim 4 is the narrowest and targets a single specific 5-O-acetyl arabinofuranosyl methoxy purine.

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FAQs

1. Does US 5,821,236 cover veterinary tumor indications as well as humans?
   The claim language includes “a mammal,” so the covered method is not limited to human patients.

2. If a competitor uses an R1 ester or salt, does that still fall within claim 1?
   Claim 1 includes “pharmaceutically acceptable ester or salt thereof,” so covered derivatives remain inside if they satisfy the R1 definition tied to formula (I).

3. Can a manufacturer avoid claim 4 by changing the sugar O-acyl position from 5-O-acetyl to 2-O-acetyl?
   Claim 4 is limited to the 5-O-acetyl compound; moving outside that exact structure avoids claim 4, though claim 1 or claim 3 exposure depends on whether the new structure falls within the enumerated set or formula (I).

4. Is US 5,821,236 limited to a specific dosage form or route of administration?
   The provided claim text specifies administering an effective tumor-inhibiting amount but does not impose a route or dosage form limitation in the method claim language shown.

5. Is this a formulation patent or a compound patent?
   It is a method-of-use patent that depends on administration of a covered compound (formula I) rather than prescribing a specific formulation composition.

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References

1. US Patent 5,821,236 (claims as provided).

Drugs Protected by US Patent 5,821,236

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: 5,821,236

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9015914	Jul 19, 1990

International Family Members for US Patent 5,821,236

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	151637
Australia	641533
Australia	8196091