Details for Patent: 4,820,738

Summary for Patent: 4,820,738

Title:	1,4-bis(substituted-amino)-5,8-dihydroxy-anthraquinones and leuco bases thereof
Abstract:	This disclosure describes symmetrical 1,4-bis(substituted-amino)-5,8-dihydroxyanthraquinones useful as chelating agents and for inducing regression and/or palliation of cancer diseases in mammals.
Inventor(s):	Keith C. Murdock, Frederick E. Durr
Assignee:	Immunex Corp
Application Number:	US06/823,265
Patent Claim Types: see list of patent claims	Use;

Scope, Claims, and U.S. Patent Landscape for US 4,820,738

What is claimed in US 4,820,738 at a claim-by-claim level?

US 4,820,738 claims methods of using specific anthraquinone-derived compounds (including leuco forms, tautomers, and pharmacologically acceptable acid-addition salts) to achieve (i) inhibition of solid tumor growth and (ii) regression of leukemia cell growth in a mammal. The claims are drafted as medical-method claims tied to defined chemical formula sets.

Claim 1: Broad method of inhibiting solid tumor growth

Claim 1 is the broadest “platform” method claim.

Core elements

• Act: “The method of inhibiting growth of solid tumors in a mammal”
• Administration: administering an “amount effective” to inhibit growth
• Compound selection: compound must be “capable of inhibiting growth of solid tumors” and must be selected from a group of compounds defined by formulae
• Q substituent definition: Q is a divalent moiety from a specified set of moieties (formula set)
• n constraint: n is 2 to 4 inclusive
• R1/R2 substituent set:
  • hydrogen
  • alkyl C1-C4
  • monohydroxyalkyl C2-C4
  • with a positional restriction: “the carbon atom alpha to the nitrogen atom may not bear an hydroxy group”
• Form coverage: includes leuco bases and tautomers and pharmacologically acceptable acid-addition salts
• Tumor susceptibility: “solid tumors being those that are susceptible to growth inhibition in said mammal by administration of said compound”

Practical scope note Claim 1 is broad on:

• indication endpoint (solid tumors broadly defined by susceptibility)
• treatment form (leuco, tautomer, salts)
• substituent variability (n 2-4; R1/R2 within defined sets)

It is constrained by the chemical formula set and the structural prohibitions on hydroxy placement alpha to nitrogen.

Claims 2 and 3: Narrowing by Q selection and listing exemplars

• Claim 2: narrows Q to —CH2CH2—
• Claim 3: identifies specific compounds within the broader formula set, listing six items:
  1. Leuco-1,4-bis[(2-dimethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
  2. 1,4-Bis[(2-dimethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
  3. Leuco-1,4-bis[(2-diethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
  4. 1,4-Bis[(2-diethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
  5. the dihydrochloride salt of 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquininone
  6. 1,4-Bis(2-aminoethylamino)-5,8-dihydroxyanthraquinone or its dihydrochloride salt

Key commercial implication Claim 3 is a “claim-to-product” bridge: it anchors the formula-based claim to named chemical species that can map cleanly to candidate drug development programs.

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How is leukemia addressed in the second claim family?

Claim 4: Broad method of inducing regression of leukemia cell growth

Claim 4 mirrors Claim 1 but swaps the endpoint:

• Act: “inducing regression of leukemia cell growth in a mammal”
• Administration: “amount effective” to induce regression
• Compound selection: same style of formula-based selection, constrained by:
  • Q divalent moiety from defined moiety set
  • n = 2 to 4
  • R1/R2 permitted sets and alpha-hydroxy restriction
  • includes leuco bases, tautomers, pharmacologically acceptable salts

Claims 5-7: Narrowing to Q and enumerated exemplars

• Claim 5: narrows Q to —CH2CH2—
• Claim 6: specifies 1,4-bis(2-aminoethylamino)-5,8-dihydroxyanthraquinone or its dihydrochloride salt
• Claim 7: provides a five-item list of specific exemplars, including:
  • Leuco-1,4-bis[(2-dimethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
  • 1,4-Bis[(2-dimethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
  • Leuco-1,4-bis[(2-diethylaminoethyl)amino]-5,8-dihyroxyanthraquinone
  • 1,4-Bis[(2-diethylaminoethyl)amino]-5,8-dihyroxyanthraquinone
  • dihydrochloride salt of 1,4-Bis[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquinone

Claims 8-11: Single-compound dependent claims

Each claim further narrows Claim 7’s list:

• Claim 8: Leuco-1,4-bis[(2-dimethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
• Claim 9: 1,4-bis[(2-dimethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
• Claim 10: Leuco-1,4-bis[(2-diethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
• Claim 11: 1,4-bis[(2-diethylaminoethyl)amino]-5,8-dihydroxyanthraquinone

Claim 12: Mammal species fallback

• Claim 12: mammal is a mouse

Practical scope note Species narrowing exists, but the core coverage is not species-limited. Claim 12 reads as a “fallback” dependent claim that can support narrower enforcement if broader mammal language faces validity or infringement arguments.

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What is the effective infringement “scope” from a chemistry-to-claim mapping?

Even without the drawings, the claim language supplies a clear structure-to-scope logic:

1) The “must-hit” scaffold

All covered compounds are anthraquinone derivatives with:

• 5,8-dihydroxy substitution
• 1,4-bis(…amino…) substitution pattern
• leuco/tautomer/salt coverage

2) The variable linker: Q and the n parameter

• Q: divalent moiety from a specified set
• n: integer 2 to 4 inclusive These two parameters define the linker region and govern whether an analog lies inside or outside.

3) The terminal amine substituents: R1/R2 set and hydroxy restriction

R1 and R2 can be:

• H
• alkyl C1-C4
• monohydroxyalkyl C2-C4, with an explicit limitation: the carbon atom alpha to nitrogen cannot bear an hydroxy group.

This is a precise medicinal-chemistry constraint. It creates an “edge” around hydroxy-substituted alkyl amines.

4) Included forms: leuco bases, tautomers, and acid-addition salts

The claims expand effective coverage beyond a single oxidation state:

• leuco forms
• tautomers
• acid-addition salts (including exemplified dihydrochlorides)

From an IP standpoint, a development program that uses different salt forms or relies on leuco interconversion has higher chance of remaining within claim coverage.

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How broad is the claim set relative to typical U.S. method-of-use drafting?

This is a classic U.S. approach for functional treatment endpoints with formula-based selection:

• Method of treatment claims (not compositions-of-matter)
• Endpoint breadth:
  • Solid tumor growth inhibition in susceptible tumors
  • Leukemia regression of cell growth
• Chemical breadth:
  • a formula-defined genus with enumerated dependent exemplars
  • explicit form coverage (leuco/tautomers/salts)

The structure means:

• infringement arguments likely hinge on whether a candidate compound falls within the formula-defined genus (Q, n, R1/R2, and alpha-hydroxy restriction)
• and whether it is used at an effective amount to achieve the claimed biological endpoint

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What does the dependent-claim hierarchy accomplish?

Solid tumor branch (Claims 1-3)

• Claim 1: broad genus for “solid tumors susceptible to growth inhibition”
• Claim 2: Q fixed to —CH2CH2—
• Claim 3: locks in specific compounds, including dimethylaminoethyl and diethylaminoethyl variants and a hydroxyethylaminoethyl variant as a dihydrochloride salt

Leukemia branch (Claims 4-12)

• Claim 4: broad genus for “regression of leukemia cell growth”
• Claim 5: Q fixed to —CH2CH2—
• Claims 6-7: narrower named compound sets
• Claims 8-11: individual named compounds
• Claim 12: mouse species

This pattern is enforcement-oriented: if the genus is challenged, the named compounds retain footholds; if leukemia-in-mammal breadth is challenged, species-specific dependent claim 12 provides an additional narrow angle.

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Key practical takeaways for the patent landscape strategy

1) Expect “formula boundary” scrutiny

Because claim coverage is governed by Q, n, and R1/R2 rules, competitive compounds that modify linker type, linker length, or the terminal substituent hydroxy pattern face non-infringement arguments on structural grounds.

2) Leuco/tautomer/salt coverage reduces design-around options

A competitor cannot easily avoid infringement by switching between:

• leuco base vs parent oxidation state
• tautomeric state
• acid-addition salt (including dihydrochloride variants)

3) Named exemplars in dependent claims matter

Claims 3 and 7-11 enumerate specific candidates. If a developer’s lead maps to one listed species, the infringement risk does not depend on litigating the full formula genus.

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Key Takeaways

• US 4,820,738 claims method-of-treatment uses of anthraquinone-derived bis-amino-substituted dihydroxyanthraquinones for solid tumor growth inhibition and leukemia cell growth regression.
• The chemical scope is defined by formula sets with Q (divalent moiety), n (2 to 4), and R1/R2 (H, C1-C4 alkyl, monohydroxyalkyl C2-C4) plus a strict “alpha carbon to nitrogen cannot bear hydroxy” rule.
• The claims explicitly include leuco bases, tautomers, and pharmacologically acceptable acid-addition salts, reducing avoidance via salt/oxidation-state variation.
• The dependency ladder (Q fixed to —CH2CH2—, then named compound lists, then individual species, then mouse) supports multiple enforcement fallback positions.

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FAQs

1) Is US 4,820,738 a composition-of-matter patent?
No. It claims methods of treating (inhibiting solid tumors; inducing leukemia regression) via administering formula-defined compounds.

2) What biological outcomes are claimed?

• Solid tumors: “inhibiting growth” of solid tumors in a mammal (tumors must be susceptible by administration of the compound).
• Leukemia: “inducing regression” of leukemia cell growth in a mammal.

3) Does the patent cover leuco forms and salts?
Yes. Claim language includes leuco bases, tautomers, and pharmacologically acceptable acid-addition salts.

4) Which dependent claims enumerate specific chemical species?

• Solid tumor branch: Claim 3 enumerates six specific compounds/salts.
• Leukemia branch: Claims 7-11 enumerate specific compounds; Claim 6 isolates one aminoethylamino compound or its dihydrochloride salt.

5) Is the claimed Q-linker flexible?
Yes under Claim 1/4 via the Q divalent moiety set, but dependent claims narrow it to —CH2CH2— (Claims 2 and 5), and the named compounds in Claims 3 and 7-11 correspond to that narrower configuration.

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References

[1] United States Patent and Trademark Office. US Patent 4,820,738. https://patents.google.com/patent/US4820738A

Drugs Protected by US Patent 4,820,738

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 4,820,738

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	225884
Austria	359484
Austria	A590678