Details for Patent: 6,916,802

Summary for Patent: 6,916,802

Title:	Amino ceramide-like compounds and therapeutic methods of use
Abstract:	The present invention provides amino ceramide-like compounds which inhibit glucosyl ceramide (GlyCer) formation by inhibiting the enzyme GlyCer synthase, thereby lowering the level of glycosphingolipids. The compounds of the present invention have improved GlcCer synthase inhibition activity and are therefore useful in therapeutic methods for treating various conditions and diseases associated with altered glycosphingolipid levels.
Inventor(s):	James A. Shayman, David J. Harris, Craig Siegel, Carol A. Nelson, Diane P. Copeland
Assignee:	Genzyme Corp , University of Michigan System
Application Number:	US10/839,497
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,916,802
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 6,916,802 Landscape Analysis: Claim Scope, Likely Claim Construction Boundaries, and US Patent Estate Risks

US 6,916,802 is a composition-of-matter and broad therapeutic-use patent anchored on “Formula I” compounds with tunable substituents at three variable positions (R1, R2, R3). The independent claim scope is wide on structural variability (broad genus at R1, defined alkyl length at R2, and a defined set of cyclic amine “R3” rings), and it also covers multiple downstream medical indications via method claims. In US practice, the main enforceability leverage comes from (1) how narrowly “Formula I” is actually limited by the patent’s specification for the “kernel,” (2) whether dependent claims add meaningful narrowing limitations or mainly restate the same genus, and (3) whether competitors can design around by altering R1/R2/R3 boundaries that are not supported as interchangeable embodiments in the specification.

What is US Patent 6,916,802 claiming in plain terms?

Direct answer: It claims a genus of stereoisomeric “Formula I” compounds (and salts/mixtures) plus methods of treating cancer, drug-resistant tumors, tumor angiogenesis, and selected glycosphingolipidoses tied to glucosylceramide.

What are the independent claim elements?

The independent claim language appears in two parallel sets (Claims 1 and 8 are composition claims; Claims 3-7 and 10-14 are method claims). The scope is driven by:

• A compound of “Formula I” (stereoisomer/salt/mixture included)
• R1:
  • phenyl or substituted phenyl, or
  • branched aliphatic group, or
  • C7–C15 alkyl chain or C7–C15 alkenyl chain with a double bond next to the kernel
• R2: alkyl group C6, C7, or C8
• R3:
  • pyrrolidine, azetidine, morpholine, or piperidine (in claim 1)
  • and pyrrolidine in claim 8, with nitrogen attached to the kernel

This structure reads as a lipophilic tail (R1) + short linker/alkyl (R2) + cyclic amine headgroup (R3) scaffold.

What do the dependent claims narrow?

Claims 2 and 9 narrow R1 substituents to phenyl functionalization patterns:

• p-methoxy
• hydroxyl
• methylenedioxy
• ethylenedioxy
• trimethylenedioxy
• cyclohexyl

Claims 7 and 14 narrow glycosphingolipidosis indications to a defined list:

• Gaucher disease
• Fabry disease
• Tay-Sachs
• Sandhoff disease
• GM1 gangliosidosis

How does the “double bond next to the kernel” limit R1?

The claim requires that for C7–C15 alkenyl substituents, the double bond is adjacent to the kernel. That means a competitor who uses a terminal or internal double bond not adjacent to the kernel is potentially outside the literal R1 definition even if the carbon count overlaps.

How does nitrogen attachment to the kernel limit R3?

For the cyclic amines, the claim states that the nitrogen atom is attached to the kernel. That limits isomeric placement for substituted rings and may exclude formulations where the amine is not connected through the claimed attachment pattern, even if the same ring exists.

How broad are the genus parameters for infringement?

Direct answer: R1 is the broadest driver (multiple classes plus C7–C15 length), R2 is moderately constrained (C6–C8), and R3 is tightly constrained to specific ring types (with a more limited R3 set in Claim 8). The dependent claims then tighten R1 substituent identity (for the phenyl series) and indication lists (for glycosphingolipidosis).

Practical claim-construction pressure points

1. What counts as “kernel”
   The phrase “next to the kernel” and “nitrogen atom is attached to the kernel” depends on how Formula I defines the core scaffold in the spec. In litigation, this is usually where the specification and drawings drive construction.

2. “Branched aliphatic group” ambiguity risk
   “Branched” is not quantified. If the specification only exemplifies certain branching motifs, courts may effectively narrow interpretive scope through intrinsic evidence. That does not eliminate literal coverage but increases design-around value.

3. Stereoisomer coverage
   Both independent composition claims explicitly include stereoisomers. That generally blocks competitors from arguing that a different stereochemistry avoids coverage if the stereochemistry is still a “stereoisomer of Formula I.”

4. Salt/mixture coverage
   Including “pharmaceutically acceptable salt or mixture” increases capture of formulation-stage salt selection and mixed stereochemistry manufacturing, assuming the base compound falls within Formula I.

Comparison: Claim 1 vs Claim 8

• Claim 1 R3 set is broader: pyrrolidine, azetidine, morpholine, or piperidine.
• Claim 8 R3 set is narrower: pyrrolidine only.

So, Claim 1 is the bigger composition net on headgroup choice. Claim 8 functions as a narrower subset focused on pyrrolidine analogs.

What do the method claims cover, and where are the enforceability chokepoints?

Direct answer: The method claims are broad on therapeutic indication framing and do not require a specific mechanism, dose, or regimen beyond “therapeutically effective amount” and that the cells are “sensitive.” The enforceability hinges on whether “sensitive” is satisfied by the competitor’s patient selection and whether “drug-resistant tumor” and “angiogenesis” are supported by the patent’s disclosure.

Cancer growth inhibition (Claims 3 and 10)

• Administer a therapeutically effective amount of the compound/composition
• Requires that “cancer cells are sensitive”

Chokepoints:

• “Sensitive to” typically invites debate on whether sensitivity is phenotypic and objective or depends on assays or biomarker presence. Competitors may attempt to steer use toward populations where sensitivity is not established.

Drug-resistant tumor treatment (Claims 4 and 11)

• Same administration concept
• Adds the tumor is “drug resistant”

Chokepoints:

• “Drug resistant” is not tied to a specific prior drug or mutation status in the claim text. Still, in practice, claim scope often turns on how intrinsic evidence defines this term in the specification and examples.

Tumor angiogenesis reduction (Claims 5 and 12)

• Requires reduced angiogenesis “in a patient”
• Again ties to “angiogenesis is sensitive”

Chokepoints:

• “Angiogenesis” endpoints are usually assay- or marker-based. Patent validity and infringement arguments can turn on what the specification discloses as measurable angiogenesis inhibition.

Glycosphingolipidosis treatment (Claims 6-7 and 13-14)

• Requires disorder associated with glucosylceramide
• Dependent claims list disease entities

Chokepoints:

• The claim ties the disorder to glucosylceramide association. This supports a mechanism-linked indication, which can narrow the patient population relative to purely symptom-based indications.
• Competitors who position their therapy for a different glycosphingolipid target or a different mechanistic axis can seek to avoid “associated with presence of glucosylceramide” limitations.

What patents protect this scaffold in the US? (Landscape based on typical estate structure)

Direct answer: Without Orange Book/FDA linkage data and without the full family/patent citation list, an exhaustive “all covering US patents” map cannot be produced from the claim text alone.

That said, for a composition genus patent like US 6,916,802, the US estate risk profile in practice usually includes:

• Continuation or divisionals: narrower R1/R2/R3 subsets, specific stereoisomers, or specific salts and intermediates.
• Method-of-use follow-ons: assays, patient selection criteria (“sensitivity” tests), and specific indication subtypes.
• Formulation/process patents: specific dosage forms, salt hydrates, particle-size control, and manufacturing intermediates.

The litigation and design-around value typically comes from whether any follow-on claims are positioned as stronger “anchor” claims against close variants (for example, by locking in more precise R1 tail structures or exact R3 substitution patterns).

How does claim scope translate into design-around options?

Direct answer: The most direct design-arounds target R1 carbon count/classes, the location of the double bond adjacent to the kernel, R2 chain length, and the R3 ring type set.

R1 design-arounds

1. Change alkyl/alkenyl chain length
   Claim requires C7–C15. C6 or C16 should avoid literal R1 alkyl/alkenyl coverage.

2. Alter alkenyl double bond position
   For C7–C15 alkenyl, the double bond must be next to the kernel. Shifting the double bond away can be a literal design-around.

3. Avoid branched aliphatic interpretation traps
   Using a straight-chain aliphatic tail instead of branched aliphatic (if “branched aliphatic” is interpreted narrowly) can avoid that branch of R1, though it may still fall under alkyl chain coverage if carbon count and class overlap.

4. If relying on phenyl substitution, avoid the enumerated set
   Claims 2 and 9 enumerate specific substituents. Using other phenyl substituents may remain within Claim 1/8 (if “substituted phenyl group” is broad and not limited by the enumerated list), but it can help avoid dependent claim constraints.

R2 design-arounds

• Claim constrains R2 to C6, C7, or C8. Using C5, C9, or higher/lower length is a clean literal path.

R3 design-arounds

• Claim 1 allows multiple amine rings. Claim 8 is pyrrolidine-only.
• Moving to azetidine/morpholine/piperidine would still be within Claim 1 if those match “R3” definitions.
• Moving outside the listed ring types is the cleanest path.

What does the claim set suggest about therapeutic intent and breadth?

Direct answer: The patent claims multiple unrelated-looking therapeutic categories (oncology and lysosomal storage/glycosphingolipid disorders). That often signals a common molecular target or a shared pharmacologic effect across disease areas. For infringement, that generally broadens the likely ways a drug is marketed and prescribed. For litigation, it increases the importance of whether “sensitivity” and indication definitions match the specification’s actual evidence.

Key exposure scenarios for a competing product

Direct answer: Exposure is highest where a competitor launches a compound structurally inside Formula I with:

• R1 in C7–C15 class,
• R2 as C6–C8,
• R3 as a listed amine ring (or pyrrolidine for the narrower subset),
• and labels or instructions that align with claimed patient populations and endpoints (cancer, drug-resistant tumor, angiogenesis reduction, or glucosylceramide-associated glycosphingolipidoses).

Likely “high-risk” scenarios

• Generic or follow-on compound with a matched scaffold and stereochemical variants
• Clinical indication expansion that tracks the claimed method language
• Use in patient subgroups marketed as having glucosylceramide-associated disease states

Likely “lower-risk” scenarios

• Structural tail chain outside C7–C15 or R2 outside C6–C8
• Alkenyl double bond not adjacent to the kernel
• Headgroup ring type not listed, or nitrogen attachment pattern altered
• Indication positioning that is not tied to glucosylceramide association, or oncology use framed outside the “sensitive” limitation

Claim map (condensed)

Claim 1 (composition): Formula I stereoisomer/salt/mixture; R1 includes phenyl substituted/branched aliphatic/C7–C15 alkyl or C7–C15 alkenyl with adjacent double bond; R2 = C6–C8 alkyl; R3 = pyrrolidine/azetidine/morpholine/piperidine (N attached).

Claim 2 (dependent composition): R1 is phenyl substituted with one of listed functional groups.

Claim 3 (method oncology): Administer compound of claim 1/2 to inhibit cancer cell growth; cells sensitive.

Claim 4 (method oncology resistance): Administer to treat drug-resistant tumor; tumor cells sensitive.

Claim 5 (method angiogenesis): Administer to reduce tumor angiogenesis; angiogenesis sensitive.

Claim 6 (method glycosphingolipidosis): Administer to treat disorder associated with glucosylceramide.

Claim 7 (dependent glycosphingolipidosis): Disorders selected from Gaucher, Fabry, Tay-Sachs, Sandhoff, GM1 gangliosidosis.

Claim 8 (composition, narrower R3): Same as Claim 1 but R3 = pyrrolidine only.

Claims 9-14: Mirror dependent narrowing (Claim 9) and method claims (Claims 10-14) with the narrower compound of Claim 8.

Key Takeaways

• US 6,916,802 is structurally broad at the genus level through Formula I with flexible R1 (including C7–C15 alkyl/alkenyl), constrained R2 (C6–C8), and defined R3 cyclic amines.
• Enforceability will turn on how “kernel” is defined in the specification and how “sensitive” is interpreted for method claims.
• Clean design-arounds follow the claim’s numeric boundaries: R1 carbon count/class, alkenyl double bond position adjacent to the kernel, and R2 chain length (C6–C8).
• Higher infringement risk aligns with both structural match and marketing/labeling that tracks the oncology and glucosylceramide-associated glycosphingolipidosis method claim language.

FAQs

1) What structural changes most directly avoid literal infringement of US 6,916,802?
Change R1 outside C7–C15 alkyl/alkenyl classes, shift alkenyl double bond away from the kernel, change R2 outside C6–C8, or use an R3 headgroup ring type not listed (and for the narrower subset, avoid non-pyrrolidine headgroups).

2) Do method claims require a specific assay or biomarker to prove “sensitivity”?
The claim text requires sensitivity, but it is not defined in the claim language itself; practical enforcement typically depends on how sensitivity is supported by the patent disclosure and how the accused product’s use population is selected.

3) Can a competitor infringe if they use a different salt form?
Yes, if the salt is a pharmaceutically acceptable salt and the underlying free base compound is within Formula I (the claim expressly covers salts).

4) Does the patent cover stereoisomers only or also all stereochemical variants?
The claims include stereoisomers of Formula I, so different stereochemistry alone does not avoid coverage if it remains within the Formula I stereoisomer set.

5) How do the dependent glycosphingolipidosis lists affect risk?
Dependent claims narrow specific disease names, but the independent glycosphingolipidosis method claim ties to glucosylceramide association, which can still capture disease states beyond the named list if they are argued to be associated with glucosylceramide.

References

1. U.S. Patent 6,916,802.

Drugs Protected by US Patent 6,916,802

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

International Family Members for US Patent 6,916,802

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	5929600
Australia	774960
Brazil	0012318
Canada	2378600
Canada	2454453
European Patent Office	1196406
European Patent Office	1384719