Details for Patent: 6,331,635

Summary for Patent: 6,331,635

Title:	Taxoids, their preparation and pharmaceutical compositions containing them
Abstract:	New taxoids of general formula (I): their preparation and pharmaceutical compositions containing them.The new products of general formula (I) in which Z represents a radical of general formula (II): display noteworthy antitumour and antileukaemic properties.
Inventor(s):	Hervé Bouchard, Jean-Dominique Bourzat, Alain Commerçon
Assignee:	Sanofi Mature IP
Application Number:	US09/066,929
Patent Claim Types: see list of patent claims	Composition; Compound;

Scope and Claim Coverage of US Patent 6,331,635 (Taxoids) and the U.S. Patent Landscape for Generic or Biosimilar Entry

US 6,331,635 is a broad “taxoid” IP patent framed around a Markush-style taxoid structural formula (Formula I), downstream ester variants (Formulas V and VII), and specific exemplified taxoid esters combined with cisplatin in pharmaceutical compositions. The claim set uses wide substituent ranges for three major substitution sites (via Z, R1/R2 and R3, plus linker/alkoxy groups R4 and R5) and then narrows in dependent claims to particular embodiments (including explicit named taxoid structures) and to combination therapy with cisplatin.

What is US Patent 6,331,635 actually claiming? (taxoid Formula I, ester formulas V/VII, and cisplatin compositions)

Core independent claim architecture: Formula (I) taxoid scaffold

Independent Claim 1 is a taxoid “of formula (I)” defined through:

• Z as either hydrogen or a radical of Formula (II).
• Formula (II) defines:
  • R1 as a benzoyl radical (optionally substituted) or a thenoyl/furoyl radical or an acyl/oxycarbonyl radical R2–O–CO– (with R2 being highly variable).
  • R2–O–CO– where R2 spans large families of alkyl/alkenyl/alkynyl/cycloalkyl/cycloalkenyl/bicycloalkyl, plus heteroatom- and functional group-substituted variants (halogens, hydroxyl, alkoxy, dialkylamino, piperidino, morpholino, piperazinyl, cyano, carboxyl, alkoxycarbonyl, etc.).
• R3 as an additional substituent on the taxoid scaffold with similarly broad permissible ranges:
  • unbranched/branched alkyl and alkenyl/alkynyl,
  • cycloalkyl,
  • phenyl or α/β-naphthyl (optionally substituted),
  • 5-membered heteroaromatic or saturated heterocycles (4–6 membered).
• R4 and R5 as alkoxy chains (each alkoxy radical containing 1–6 carbons, unbranched or branched).

Practical claim takeaway: Claim 1 covers a very wide genus of taxoid esters/derivatives by allowing broad combinatorial variation at multiple substituent positions. This kind of Markush breadth increases coverage probability against multiple “nearby” analogs and salts/variants that keep the same core scaffold but alter acyl/oxycarbonyl groups, ring substituents, and alkoxy sidechains.

Dependent claim narrowing: explicit embodiment restrictions (Claims 2–6 and 3-tert-butyl/heteroaryl variants)

Claims 2–4 progressively restrict the genus:

• Claim 2 narrows Formula (II) options:
  • Z is H or Formula (II) where R1 is benzoyl or an oxycarbonyl radical with R2 = tert-butyl.
  • R3 restricted to alkyl (1–6C), alkenyl (2–6C), cycloalkyl (3–6C), optionally substituted phenyl or specific heteroaryl rings (furyl, thienyl, thiazolyl positional set).
• Claim 3 further specifies a tighter list of R3 substituents (including specific furyl/thienyl/thiazolyl) and restricts R4/R5 to methoxy/ethoxy/propoxy.
• Claim 4 narrows further when R2 is a 5-membered aromatic heterocycle to furyl/thienyl.

Practical claim takeaway: These dependent claims give “fallback” positions that will often be easier to prove in infringement than Claim 1’s full breadth because they map onto discrete chemical design choices (benzoyl vs tert-butyl oxycarbonyl; specific heteroaryl R3; methoxy/ethoxy/propoxy R4/R5).

Explicit chemical exemplars: named taxoid structures (Claims 5–6, 12, and 13 plus ester exemplars implied)

Claims 5 and 6 recite two specific taxoid molecules by name-like stereochemical descriptors (across taxen core elements) including:

• “4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-10β-ethoxy-…-7β-methoxy-…”
• “4α-acetoxy-2α-benzoyloxy-…-10β-(1-propyl)oxy-…”
• Both include the “13α-yl(2R,3S)-3-…-2-hydroxy-3-phenylpropionate” substituent details, including tert-butoxycarbonylamino protection.

Claim 12 and the later numbered exemplars also recite additional explicit taxoid/ester structures, including a more complex oxazolidine and methoxyphenyl variant.

Practical claim takeaway: The presence of explicit enumerated compounds is key for infringement risk assessments. Even if a candidate design tries to stay within the core Markush genus but changes stereochemistry, those enumerated examples can anchor literal infringement arguments for at least those specific molecules.

Independent claims on ester families: Formulas V and VII (Claims 10–11)

Claims 10 and 11 claim “an ester” of Formula (V) and Formula (VII), respectively, again with:

• R1 and R2 oxygen-carbonyl acyl substituent diversity,
• R3 diversity,
• R4 and R5 alkoxy diversity,
• plus extra features in Claim 10:
  • either R6 = hydrogen and R7 is a protecting group for hydroxyl function, or
  • R6 and R7 together form a saturated 5- or 6-membered heterocycle.

Practical claim takeaway: The “ester” claims can capture prodrugs, protected intermediates, or formulation-related derivatives that may not be identical to the “taxoid” Claim 1 compound, depending on what protec groups or cyclic protecting groups are retained in the marketed entity.

Combination therapy claims: taxoid + cisplatin (Claims 7, 8, 16–25)

Claim 7 introduces a pharmaceutical composition:

• “A pharmaceutical composition comprising at least one product according to claim 1… in combination with one or more pharmaceutically acceptable diluents… and optionally one or more compatible and pharmacologically active compounds.”

Claims 8–9 narrow to Claim 5 and Claim 6 embodiments.

Claims 16–25 specifically add cisplatin:

• Claim 16: pharmaceutical composition where the compatible pharmacologically active compound is cisplatin.
• Claims 20–22 and 23:
  • compositions containing specific named taxoid esters plus cisplatin.
• Claims 25:
  • cisplatin is present in a composition based on Claim 24’s structure/conditions.

Practical claim takeaway: If any generic or “design-around” product uses the same taxoid (or a covered genus member) in a cisplatin combination, the combination claims create a second line of infringement exposure even if the taxoid-only coverage is contested.

How broad is the structural scope? (substituent freedom at Z, R1/R2, R3, R4/R5)

Z variable: hydrogen vs acyl/oxycarbonyl radical (Formula II)

Z being H or substituted by Formula (II) is a “branch point”:

• If Z = H, the taxoid retains one set of functional group patterns.
• If Z = Formula (II), then R1 is benzoyl/thenoyl/furoyl/oxycarbonyl-acyl type and R2 drives substantial acyl diversity.

The breadth here is substantial: R1 includes benzoyl (optionally substituted) and thenoyl/furoyl plus R2–O–CO– variants; R2 includes diverse carbon frameworks and functional substituents.

R1 freedom and “acyl-like” coverage

R1 allows:

• benzoyl radicals with halogen/alkyl/alkoxy/trifluoromethyl substitutions,
• thenoyl and furoyl radicals,
• and an oxycarbonyl radical R2–O–CO–.

Infringement implication: Many medicinal chemistry modifications that swap acyl groups (benzoyl vs other aromatic acyl, or change the oxycarbonyl R2) can stay within the claim set if they retain:

• the same taxoid core and stereochemical framework,
• the same connection points and general radical definitions.

R3 freedom: aryl/heteroaryl and saturated heterocycles

R3 includes large families:

• hydrocarbyl (alkyl, alkenyl, alkynyl),
• cycloalkyl,
• phenyl/naphthyl optionally substituted with halogen/alkyl/alkoxy,
• 5-membered aromatic heterocycles,
• saturated heterocycles (4–6 members).

Infringement implication: If a competitor keeps the “R3 attachment logic” but changes the aromatic/heteroaryl ring identity or adds modest substituents, Claim 1 and its dependent variants may still cover.

R4 and R5: alkoxy chain lengths capped at C6

R4 and R5 are alkoxy (1–6 carbons) unbranched or branched. Dependent claims often restrict them to methoxy/ethoxy/propoxy.

Infringement implication: The highest design-around leverage is likely here. If a candidate product uses longer alkoxy groups or changes to non-alkoxy substituents at those positions, it may fall outside R4/R5 definitions. But staying within those ranges maintains claim coverage.

What claim elements likely matter most in infringement analysis? (literal infringement targets)

For taxoid-only products

A typical infringement mapping would check:

1. Whether the marketed “taxoid” has the taxoid core with the relevant scaffold captured by Formula (I).
2. Whether Z is hydrogen or bears the specific acyl/radical pattern of Formula (II).
3. Whether R1/R2/R3 correspond to any allowed members.
4. Whether R4 and R5 are alkoxy (1–6 carbons) and, for dependent claims, whether they are restricted to methoxy/ethoxy/propoxy.
5. Whether stereochemical configuration matches the exemplified named claims (for Claims 5–6, 12, 20–22, etc.), since those are explicitly defined.

For combination products

Even if the taxoid structure is contested, combination claims require:

• a taxoid covered by the referenced claim (Claim 1 genus or particular exemplars) being administered in a pharmaceutical composition,
• with cisplatin as the pharmacologically active compound (Claim 16 and the specific composition claims).

What other US claims are included implicitly by the ester family? (protected hydroxyl vs cyclic R6/R7)

Claim 10’s option:

• either R6 = H and R7 is a hydroxyl protecting group,
• or R6 and R7 form a saturated heterocycle.

This is often where process/formulation or prodrug chemistry can diverge. If a marketed compound retains protecting groups or is converted into a protected intermediate before administration, ester/protecting group claims can matter.

What patent landscape questions arise from a wide Markush genus like this?

How many “coverage entry points” exist?

From the claim text alone, the patent creates multiple infringement pathways:

• Taxoid genus coverage (Claim 1).
• Dependent genus subsets (Claims 2–4 and restrictions on R2/R3/R4/R5).
• Literal coverage for enumerated structures (Claims 5–6, 12 and other explicit compounds).
• Ester/protected forms (Claims 10–11, 14–15).
• Combination with cisplatin (Claims 16–25, plus compositions defined around exemplars).

Business implication: A designer-around must avoid all relevant substitution definitions and also avoid cisplatin co-formulation if those combination claims are active and apply to the intended regimen.

Which claim strategy is most likely to survive validity challenges?

Without litigation context, the structural strategy is still clear:

• The explicit compounds (e.g., Claims 5–6 and 12 and the named cisplatin combinations) are typically easier to map to prior art and typically easier to prove infringement for.
• The broad genus can be harder to invalidate in full if at least one embodiment has strong support and the priority disclosure matches the covered genus members. This patent’s claim set includes both broad genus and specific exemplars, which often improves enforcement posture: you can assert the broad claim if you can, otherwise rely on narrower dependent claim coverage.

What is the scope of pharmaceutical composition claims with cisplatin?

How the compositions are drafted

The compositions are written to include:

• at least one product from the taxoid claims (depending on which composition claim),
• pharmaceutically acceptable diluents/adjuvants,
• optionally other pharmacologically active compounds,
• and in specific dependent claims, cisplatin is expressly identified.

Practical enforcement relevance

For business risk modeling, cisplatin combination claims usually:

• increase the number of products that can trigger infringement (any taxoid analog used with cisplatin),
• reduce freedom to alter formulation without changing active ingredient identity.

Key takeaways

• US 6,331,635 is a broad, Markush-style taxoid patent covering a wide genus of taxoid derivatives via Formula (I) with variable Z, acyl/oxycarbonyl substitution (R1/R2), and substituent diversity at R3, plus alkoxy chain definitions at R4/R5.
• The claim set includes both genus claims (Claim 1) and multiple narrower dependent claims restricting key substituent families (Claims 2–4).
• The patent also includes explicitly recited taxoid structures (Claims 5–6, 12, and other explicit embodiments) that can support literal infringement theories.
• Separate ester/protected hydroxyl claims (Claims 10–15) broaden coverage to related derivative forms and protection-state variations.
• Pharmaceutical composition claims add an enforcement lever around cisplatin combination therapy (Claims 16–25), which can capture products even when taxoid-only coverage is harder to prove.

FAQs

1) Does US 6,331,635 cover only one taxoid, or a chemical class?

It covers a chemical class: Claim 1 is a taxoid genus defined by Formula (I) with broad ranges for R1/R2, R3, R4, and R5, and Z as hydrogen or Formula (II).

2) What part of the structure can be most effective for design-around?

R4 and R5 are limited to alkoxy radicals containing 1–6 carbons, and dependent claims restrict them further to methoxy/ethoxy/propoxy. Altering those positions outside the defined alkoxy families is the clearest route suggested by the claim language.

3) Are “protected” hydroxyl forms within the scope?

Yes. The ester claim family (notably Claim 10) defines either a free hydroxyl with a protecting group (R6 = H; R7 = protecting group) or cyclic heterocycle formation via R6/R7, which expands coverage to hydroxyl-protection states.

4) If a competitor uses a different platinum drug than cisplatin, are the combination claims still relevant?

The explicitly cisplatin-identified composition claims (Claims 16 and dependent enumerated cisplatin compositions) are tied to cisplatin as the active compound. Non-cisplatin combinations would not literally match those dependent limitations, though the broader composition language that is not limited to cisplatin may still matter depending on which claims are asserted.

5) Are there multiple “infringement entry points” beyond the taxoid itself?

Yes. The patent includes taxoid genus (Claim 1), specific taxoid exemplars (Claims 5–6, 12, etc.), ester forms (Claims 10–15), and pharmaceutical compositions including cisplatin (Claims 16–25). A product can fall under one or more of these categories.

References

1. United States Patent No. 6,331,635 (claim text as provided in prompt).

Drugs Protected by US Patent 6,331,635

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: 6,331,635

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	95 03545	Mar 27, 1995
France	95 15381	Dec 22, 1995

International Family Members for US Patent 6,331,635

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	753
African Regional IP Organization (ARIPO)	785
African Regional IP Organization (ARIPO)	9701090
African Regional IP Organization (ARIPO)	9701093