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:
- 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-dihydroxyanthraquinone
- 1,4-Bis[(2-diethylaminoethyl)amino]-5,8-dihydroxyanthraquinone
- the dihydrochloride salt of 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquininone
- 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.
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.
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.
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
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.
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.
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.
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.
References
[1] United States Patent and Trademark Office. US Patent 4,820,738. https://patents.google.com/patent/US4820738A
