Details for Patent: 6,316,471

Summary for Patent: 6,316,471

Title:	Isoindolines, method of use, and pharmaceutical compositions
Abstract:	Substituted 2-(2,6-dioxopiperidin-3-yl)phthalimides and 1-oxo-2-(2,6-dioxopiperidin-3-yl)isoindolines reduce the levels of TNFα in a mammal. Typical embodiments are 1-oxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4,5,6,7-tetrafluoroisoindoline and 1,3-dioxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4-aminoisoindoline.
Inventor(s):	George W. Muller, David I. Stirling, Roger Shen-Chu Chen
Assignee:	Celgene Corp
Application Number:	US09/634,061
Patent Claim Types: see list of patent claims	Use; Composition; Delivery; Dosage form;

Scope, Claims, and Patent Landscape Analysis for US 6,316,471

US 6,316,471 is a method-and-composition patent that claims treatment of inflammation, autoimmune and inflammatory diseases, and oncogenic/cancerous conditions using a specific “compound of the formula” (and its acid addition salts). The claim set is broad on (i) indication categories, (ii) route of administration, and (iii) combination therapy, but it is constrained to the specific chemical structure(s) defined in the patent’s missing “formula” and salt scope. Without the formula text and the specification-defined exemplars, the exact chemical boundaries cannot be reconstructed.

What do the independent claims cover?

Claim 1 (methods of treating inflammation and immune-mediated disease)

Claim 1 claims:

• A method of treating “inflammation, inflammatory disease or autoimmune disease” in a mammal
• by administering an effective amount of:
  • “a compound of the formula:” (formula not provided in the prompt), or
  • an acid addition salt of that compound

Scope drivers

• Indication breadth: inflammation and autoimmune diseases are both covered.
• Mammal breadth: includes “a mammal” without limiting species.
• Dosing standard: “effective amount” is functional, not dose-quantified.
• Chemical constraint: limited to compounds that fall within the patent-defined formula and its acid addition salts.

Claim 16 (methods of treating oncogenic/cancerous conditions)

Claim 16 claims:

• A method of treating “an oncogenic or cancerous condition” in a mammal
• by administering an effective amount of:
  • “a compound of the formula:” (formula not provided), or
  • an acid addition salt

Scope drivers

• Oncology breadth: no tumor type or stage limitations.
• Same compound constraint: same formula + salts.

Claim 21 (composition claim tied to the same compound family)

Claim 21 claims a pharmaceutical composition:

• comprising a compound of the formula or an acid addition salt
• plus “a pharmaceutically and physiologically suitable carrier”
• in a quantity sufficient upon dosing in single or multiple regimens to produce at least one of:
  • improving an oncogenic/cancerous condition
  • reducing inflammation
  • improving autoimmune disease

Scope drivers

• Use-flexible effect language: only one of the three listed effects is needed.
• Form not limited in the independent claim (dosage forms appear in dependent claim 22).
• Carrier-inclusive: typical formulation scope.

How broad are the dependent claims on indications?

The dependent claims convert the category language into specific labeled disease examples while staying within the same method frame (claims 1 or 16).

Inflammation/autoimmune/inflammatory disease ladder (dependent to Claim 1)

• Claim 2: rheumatoid arthritis
• Claim 3: osteoarthritis
• Claim 4: inflammatory bowel disease
• Claims 5-6: Crohn’s disease; ulcerative colitis
• Claim 7: arthritic condition
• Claim 8: sepsis
• Claim 9: lupus
• Claim 10: erythema nodosum leprosum

Takeaways on how the dependency works

• The dependent claims do not narrow the chemistry; they narrow the disease framing.
• They strengthen enforceability for those named indications by eliminating ambiguity about whether a disease fits the “inflammation/inflammatory disease/autoimmune disease” umbrella.

Oncology ladder (dependent to Claim 16)

• The prompt does not list oncology-specific dependent indications beyond administration and combination limitations (claims 17-20 focus on route and combination, not tumor categories).

How broad is administration scope and route coverage?

Oral vs parenteral (method claims)

• Claim 11: oral or parenteral administration
• Claim 14: oral administration
• Claim 15: parenteral administration

These create essentially three enforceable method buckets:

1. any-route (claim 11)
2. oral-only (claim 14)
3. parenteral-only (claim 15)

Combination therapy (method claims)

• Claim 12: compound administered in combination with a therapeutic agent
• Claim 13: therapeutic agent is a steroid, antibiotic or neoplastic agent

This is a meaningful scope expansion because it covers combination regimens that do not require the compound to be the sole active.

Composition form factors

• Claim 22: dosage form is selected from:
  • powder
  • tablets
  • capsules
  • injectable compositions

This supports enforcement across most standard commercial oral and injectable formats.

How does the patent handle “acid addition salts”?

All independent claims (1, 16, 21) cover:

• “a compound of the formula” or
• “an acid addition salt thereof”

This typically expands freedom-to-operate risk from the free base to salt forms. Even if a competitor avoids the exact free base, it may still fall in scope if it uses an “acid addition salt” that the patent recognizes as within the defined salt class or exemplified salts in the specification.

What is the claim structure’s legal effect on enforcement?

The patent is built with three parallel independent rails:

1. Method for inflammation/autoimmune (Claim 1)
2. Method for oncology (Claim 16)
3. Pharmaceutical composition producing therapeutic effect (Claim 21)

Each rail has dependent claims for:

• specific diseases (for the inflammation rail)
• route (oral/parenteral) for method rails
• combination therapy categories
• dosage forms (composition rail)

This structure increases enforcement flexibility:

• If a generic competitor launches a product with the same compound/formula, the composition claim can be asserted directly.
• If they avoid the same composition but use the same compound in a treatment regimen, the method claims remain targets.
• If they attempt to design around by restricting route or avoiding combination, there are still independent “any-route” claim versions unless the competitor can definitively carve out all covered routes and all covered regimen structures.

Where are the claim constraints (what is NOT broad)?

Chemical limitation is the primary constraint

Every claim depends on:

• “a compound of the formula:” (not provided in the prompt)
• and “acid addition salt thereof”

Without the formula itself (including substituent identities, stereochemistry, variable definitions, ring systems, and salt definitions), no defensible determination can be made about whether a given marketed API falls within scope.

Indication coverage is broad, but not limitless

The inflammation/autoimmune examples are explicit, but they still sit inside the biologic categories asserted:

• inflammation/inflammatory disease/autoimmune disease (Claim 1 and dependent claims)
• oncogenic/cancerous condition (Claim 16)

If a competitor targets a disease outside those categories, claim fit becomes a legal construction exercise. The dependent claim list includes sepsis and lupus, which tend to be litigated disease-category boundaries.

What is the patent landscape posture for US 6,316,471 (high-level)?

Landscape inference from claim type

US 6,316,471 is a classic “second-layer” type claim set (method + formulation + broad therapeutic effect categories). Such patents commonly face landscape pressure from:

• earlier filings covering the same chemical entity
• later filings that refine specific salts, specific dosing regimens, or specific combination regimens
• competitor design-around around the chemical formula (avoidance of the defined structure) rather than around the clinical method language (because the method categories are broad)

Competitive risk points

Given the breadth of:

• inflammation/autoimmune diseases
• oncology indication category
• oral and parenteral routes
• combination therapy with steroid/antibiotic/neoplastic agent
• dosage forms including injectables

The primary design-around axis is almost certainly chemistry (formula boundaries and specific salt selection). If chemistry is unchanged, the landscape risk is high because there are multiple claim angles.

What can be said about scope without the formula text?

What can be analyzed from the provided text alone:

Scope summary (functionally)

• Therapeutic area coverage: anti-inflammatory, immunomodulatory/autoimmune, and oncology.
• Route coverage: oral and parenteral.
• Combination coverage: steroids, antibiotics, and neoplastic agents.
• Formulation coverage: powder, tablets, capsules, injectable compositions.
• Salt coverage: acid addition salts.

Scope summary (legally)

• Independent claims are tied to the same chemical formula family.
• Dependent claims specify diseases only for the inflammation/autoimmune rail.
• Composition claim is effect-linked but not indication-limited (any one of three effects is sufficient).

Practical claim-by-claim scope map

Claim	Claim type	What must be administered / provided	Indications covered in claim text	Route/form	Combination
1	Method	Effective amount of compound of “formula” or acid addition salt	Inflammation, inflammatory disease, autoimmune disease	Mammal; route not limited in claim 1 text provided	Not required
2	Dependent	Same as Claim 1	Rheumatoid arthritis	Same as Claim 1	Not added
3	Dependent	Same as Claim 1	Osteoarthritis	Same	Not added
4	Dependent	Same as Claim 1	Inflammatory bowel disease	Same	Not added
5	Dependent	Same as Claim 4	Crohn’s disease	Same	Not added
6	Dependent	Same as Claim 4	Ulcerative colitis	Same	Not added
7	Dependent	Same as Claim 1	Arthritic condition	Same	Not added
8	Dependent	Same as Claim 1	Sepsis	Same	Not added
9	Dependent	Same as Claim 1	Lupus	Same	Not added
10	Dependent	Same as Claim 1	Erythema nodosum leprosum	Same	Not added
11	Dependent	Same as Claim 1	Same category	Oral or parenteral	Not required
12	Dependent	Same as Claim 1	Same category	Same	Yes, with therapeutic agent
13	Dependent	Same as Claim 12	Same category	Same	Therapeutic agent is steroid, antibiotic or neoplastic agent
14	Dependent	Same as Claim 1	Same category	Oral	Not added
15	Dependent	Same as Claim 1	Same category	Parenteral	Not added
16	Method	Effective amount of compound of “formula” or acid addition salt	Oncogenic or cancerous condition	Mammal; route not limited in claim 16 text provided	Not required
17	Dependent	Same as Claim 16	Same oncology category	Oral	Not added
18	Dependent	Same as Claim 16	Same	Parenteral	Not added
19	Dependent	Same as Claim 16	Same	Same	Yes, with therapeutic agent
20	Dependent	Same as Claim 19	Same	Same	Therapeutic agent is steroid, neoplastic agent or antibiotic
21	Composition	Compound of formula or acid addition salt + pharmaceutically suitable carrier	Improving oncogenic/cancerous condition OR reducing inflammation OR improving autoimmune disease	Single or multiple dose regimen; dosage form not specified here	Not added
22	Dependent	Same as Claim 21	Same effect set	Powder, tablets, capsules, injectable compositions	Not added
23	Dependent	Same as Claim 21	Same	Same	Yes, with therapeutic agent
24	Dependent	Same as Claim 23	Same	Same	Therapeutic agent is steroid
25	Dependent	Same as Claim 23	Same	Same	Therapeutic agent is antibiotic
26	Dependent	Same as Claim 23	Same	Same	Therapeutic agent is antineoplastic agent

Key Takeaways

• US 6,316,471 claims the same chemical formula family (plus acid addition salts) across three enforceable angles: inflammation/autoimmune methods (Claim 1), oncology methods (Claim 16), and effect-based compositions (Claim 21).
• The patent is broad on therapeutic categories and broad on administration (oral and parenteral) and broad on combination therapy (steroid, antibiotic, neoplastic agent).
• The main boundary for scope and design-around risk is the missing chemical “formula” definition in the prompt; without it, competitors can only infer risk generally, not confirm inclusion or exclusion.
• The inflammation rail has explicit disease examples (RA, OA, IBD including Crohn’s and UC, sepsis, lupus, erythema nodosum leprosum), strengthening enforceability for those indications.

FAQs

1. Does US 6,316,471 cover both methods and compositions?
   Yes. It includes method claims for inflammation/autoimmune (Claim 1) and oncology (Claim 16), plus a pharmaceutical composition claim (Claim 21).

2. Are oral and injectable uses both covered?
   Yes. The patent includes oral and parenteral routes (Claims 11, 14, 15) and covers injectable compositions as a dosage form (Claim 22).

3. Does the patent cover combination therapy?
   Yes. Claims 12-13 cover combinations for the inflammation/autoimmune method claims, and Claims 19-20 cover combinations for oncology method claims. Composition combinations are covered by Claims 23-26.

4. Which specific diseases are named under the inflammation/autoimmune claims?
   Rheumatoid arthritis (Claim 2), osteoarthritis (Claim 3), IBD (Claim 4) including Crohn’s (Claim 5) and ulcerative colitis (Claim 6), arthritic condition (Claim 7), sepsis (Claim 8), lupus (Claim 9), and erythema nodosum leprosum (Claim 10).

5. Is the chemical scope limited to free base only or does it include salts?
   It includes “acid addition salts” alongside the compound of the formula in all core claims (Claims 1, 16, 21).

References

[1] US 6,316,471 (United States Patent). Claims provided in prompt text.

Drugs Protected by US Patent 6,316,471

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 6,316,471

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0925294		91359	Luxembourg
European Patent Office	0925294		CA 2007 00054	Denmark
European Patent Office	0925294		07C0056	France
European Patent Office	0925294		SPC033/2007	Ireland
European Patent Office	0925294		SPC/GB07/047	United Kingdom