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Patent landscape, scope, and claims: |
United States Patent 5,457,105: Scope, Claim Architecture, and US Landscape
US Patent 5,457,105 is a broad chemical and use patent built around quinazoline derivatives having a defined core structure (“formula I”) with extensive “variable-group” substitution definitions, plus explicit carve-outs that exclude a short list of specific anilino-quinazolines. The claims then broaden into compositions and methods for anti-cancer and receptor tyrosine kinase (RTK) inhibition in warm-blooded animals.
This is not a single-compound patent. It is a platform-style Markush claim set that covers a large substitution space defined by:
- the position variable m (1, 2, or 3),
- substituent sets R1 and R2 with long enumerations and generic (1–4C) / (2–4C) substituent classes,
- salts,
- plus a method-of-use backbone tied to RTK-driven malignancies and proliferative disease.
What is actually claimed in US 5,457,105? (Core chemical scope)
Formula-definition backbone (chemical claims 1-6 and dependent narrowing)
The independent chemical claim sets the product as:
- “A quinazoline derivative of the formula I”
- with:
- m = 1, 2 or 3
- each R1 selected independently from a very large list of substituents (phenolic, amino, carboxy, carbamoyl, ureido, alkoxycarbonyl, carbamoyl-containing variants, halogenated ether variants, alkyl/alkoxy classes, alkylene-dioxy, thioether/sulfinyl/sulphonyl, bromomethyl/dibromomethyl, and extensive substituted anilino/phenoxy/phenylthio/cyano/halogeno-alkoxy patterns)
- n = 1 or 2
- each R2 independently selected from another large list, including hydrogen and a broad set of heteroatom-bearing and halogenated alkyl/alkoxy, plus sulfone/sulphinyl variants and nitro/cyano/trifluoromethyl.
Salts are included via “pharmaceutically acceptable salt thereof.”
Exclusions carve-outs (hard boundaries)
Claim 1 includes an explicit “except that” exclusion list. The excluded structures are:
- 4-(4'-hydroxyanilino)-6-methoxyquinazoline (and hydrochloride salt)
- 4-(4'-hydroxyanilino)-6,7-methylenedioxyquinazoline
- 6-amino-4-(4'-aminoanilino)quinazoline
- 4-anilino-6-methylquinazoline (and hydrochloride salt)
- 4-anilino-6,7-dimethoxyquinazoline (and hydrochloride salt)
These carve-outs are repeated in multiple claim tiers, shifting slightly depending on which R1/R2 option sets apply in the dependent claims (claims 4-6 use the same carve-out logic in condensed form).
Claims 1-6 define breadth; claims 7-9 identify exemplars
The claim set has a clear escalation:
- Claims 1-6 define a broad Markush chemical genus with substitution variables and carve-outs.
- Claims 7-9 then list specific selected quinazoline derivatives (named chemical examples) inside the genus boundaries:
- claim 7 lists 7 named compounds (e.g., 4-(3'-chloro-4'-fluoroanilino)-6,7-dimethoxyquinazoline; 6,7-diethoxy-4-(3'-methylanilino)quinazoline; 4-(3'-methylanilino)-6-ureidoquinazoline, etc.)
- claim 8 provides another list with a different selection of R1 patterns (e.g., 6,7-di-(2-methoxyethoxy)-4-(3'-methylanilino)quinazoline appears later too)
- claim 9 gives 3 selected compounds.
How broad is claim 1 in practice? (R1/R2 substitution mechanics)
Claim 1 is written as a wide chemical Markush structure. Its practical scope is determined by the interaction of:
- Core substitution location controlled by m = 1–3
- Multiplicity controlled by n = 1 or 2
- The substituent sets:
- R1 list: includes aromatic-like substituents (anilino, phenoxy, phenylthio), heteroatom-rich groups (hydroxy, amino, carboxy, carbamoyl, ureido), alkyl/alkoxy and functionalized alkyl variants; includes “methyl amino,” “dimethylamino,” “piperazin-1-yl” patterns, and many ether-linked motifs.
- R2 list: includes a shorter but still broad set with hydrogen plus halogen and pseudo-halogen (fluoro/chloro/bromo by “halogeno” and explicit R2 options in dependent claims), nitro, cyano, trifluoromethyl, amino-containing groups, alkyl/alkoxy and thioether and sulfinyl/sulphonyl.
Claim 1 scope constraint: genus is large but anchored
Claim 1 does not cover “any quinazoline.” It requires the formula I architecture and then restricts substitution types through R1/R2 sets. It also imposes named exclusions that carve out at least five “anchor” members that would otherwise sit within common “anilino-quinazoline” space.
What do the dependent claims do to the chemical scope?
Claim 2: slightly different R2 option set and additional R2 members
Claim 2 is still broad, but it alters the R2 list and the allowed “R1” and “benzamido / benzenesulphonamido optional substitution” framing. It maintains the same exclusion list for the same key members:
- excludes 4-(4'-hydroxyanilino)-6-methoxyquinazoline (and HCl salt),
- 4-(4'-hydroxyanilino)-6,7-methylenedioxyquinazoline,
- 6-amino-4-(4'-aminoanilino)quinazoline,
- 4-anilino-6-methylquinazoline (HCl salt),
- 4-anilino-6,7-dimethoxyquinazoline (HCl salt).
Claim 3 and Claim 4: narrower R1 sets by removing many groups
These dependent claims progressively narrow the allowed R1 substituent types while retaining the same exclusion concept.
- Claim 3 narrows R1 list substantially compared with claim 1 (notably removing many R1 categories such as ureido appears only selectively; many bulky substituent variants are removed; the remaining options still include amino, carboxy, carbamoyl, many alkoxyalkyl patterns, and benzamido/benzenesulphonamido families).
- Claim 4 narrows further:
- it restricts R1 to a smaller set (hydroxy/methoxy type features, alkyl/alkoxy, limited amino variants, carboxy/alkoxycarbonyl, limited ureido/benzenesulphonamido)
- it keeps n = 1 or 2 and R2 as a set of hydrogen and halogenated or nitro/cyano/trifluoromethyl and alkyl/alkoxy classes.
Claim 5 and Claim 6: “product subset” definition by enumerated R1/R2
- Claim 5 is a refined genus subset. It specifies explicit R1 options like methoxycarbonyl/ethoxycarbonyl, a set of (6- or 7-) methoxy/ethoxy/propoxy/isopropoxy/butoxy groups, methylenedioxy/ethylenedioxy, and many named side-chain types such as:
- “methoxymethyl,” “piperidinomethyl,” “morpholinomethyl,” “piperazin-1-ylmethyl,” “methoxyethoxymethyl,” “carbamoylmethoxy,” “2-dimethylaminoethoxy,” “2-methoxyacetoxy,” etc.
- Claim 6 is a still tighter selector:
- it defines (R1)m as a fixed list of possible R1 substitution patterns and
- (R2)n as a list of explicit aryl-aniline-substituent-like variants (hydrogen and a set of primed substituents, including fluoro/chloro/bromo/dichloro/trifluoromethyl/nitro/methyl),
- and allows acid-addition salts.
Claims 7-9: named compounds within the genus
These claims effectively lock in:
- a set of discrete members that are still within the broader genus but function as additional claim coverage for known exemplars.
What is claimed beyond chemistry? (Compositions and methods)
Pharmaceutical compositions (claims 10-11)
- Claim 10: “A pharmaceutical composition which comprises a quinazoline derivative of the formula I …” with the same genus scope as claim 1, salts included, and a narrower exclusion in the text provided (“except that 4-anilino-6,7-dimethoxyquinazoline or the hydrochloride salt thereof are excluded”).
- Claim 11: similar composition claim with a different exclusion statement: “except that 4-anilino-6,7-dimethoxyquinazoline or the hydrochloride salt thereof are excluded” (as shown in the excerpted claim text, though the claim text you provided contains internal variations like “4-anilino-6,7-dimethoxyquinazoline” vs “4-anilino-6,7-dimethoxyquinazoline or the hydrochloride salt thereof” depending on claim number).
Methods of treatment (claims 12-21)
There is a clear typology:
- Anti-cancer effect in a warm-blooded animal via administering an effective amount of the formula I compound (claim 12).
- Same idea but further specified:
- receptor tyrosine kinase sensitive cancers (claim 15),
- “selected RTK sensitive cancer” across a list of malignancies (claim 16),
- anti-proliferative and RTK inhibition mediated by receptor tyrosine kinase (claims 17-18),
- disease/condition mediated by enzyme RTK (claim 21).
A key legal feature is that the method claims do not require a specific cancer type in the earliest method claims. They progressively introduce specificity:
- claim 15 ties to “receptor tyrosine kinase sensitive cancer,”
- claim 16 lists leukemia, breast, lung, colon, rectal, stomach, prostate, bladder, pancreatic, ovarian.
RTK inhibitory effect and therapeutic framing (claims 19-21)
- claim 19: method for treating malignant cell proliferation characterized by inhibition of RTK
- claim 20: method for producing RTK inhibitory effect
- claim 21: method for treating a disease/medical condition mediated alone or in part by enzyme RTK
These claims align the therapeutic theory tightly with RTK inhibition, supporting broad enforcement across RTK-driven oncology settings.
Do any dependent method claims lock in specific named compounds?
Yes. Claims 23-29 provide additional coverage by naming individual quinazoline derivatives tied to anti-cancer effect administration. Examples shown include:
- claim 23: 6-amino-4-(3'-methylamino)quinazoline
- claim 24: 6-acetamido-4-(3'-methylanilino)quinazoline
- claim 25: 6-(2-methoxyethylamino)-4-(3'-methylanilino)quinazoline
- claim 26: 6-methoxy-7-(2-methoxyethoxy)-4-(3'-methylanilino)quinazoline
- claim 27: 4-(3'-chloro-4'-fluoroanilino)-6,7-dimethoxyquinazoline
- claim 28: 6-(2-chloroacetamido)-4-(3'-methylanilino)quinazoline
- claim 29: 6-methylamino-4-(3'-methylanilino)quinazoline
These are enforceable even if the generic genus coverage is attacked, depending on claim construction and prosecution history not provided here.
What is the likely patent landscape structure around US 5,457,105? (Landscape logic from claim design)
Without prosecution history, assignee, priority details, or bibliographic identifiers beyond the claim text, the landscape can be mapped only by scope mechanics visible in the claims:
1) Competitor targets will likely cluster around the excluded “anchor” quinazolines
Because the claims explicitly exclude:
- 4-(4'-hydroxyanilino)-6-methoxyquinazoline
- 4-(4'-hydroxyanilino)-6,7-methylenedioxyquinazoline
- 6-amino-4-(4'-aminoanilino)quinazoline
- 4-anilino-6-methylquinazoline
- 4-anilino-6,7-dimethoxyquinazoline
(and hydrochloride salts for at least some),
a common freedom-to-operate pattern is:
- either design around by selecting members of the genus that remain inside the platform substitutions but do not match excluded members,
- or choose compounds outside the platform (different quinazoline core substitution logic, different ring systems, different kinase binding modes, or different scaffold classes).
2) The breadth invites “substituent switching” design-arounds
Claim 1 allows extremely wide switching of R1 and R2 substitution types:
- amino to carbamoyl to ureido to alkoxycarbonyl and to thioether/sulfonyl/halomethyl variants,
- alkoxy and alkylenedioxy ring patterns,
- anilino/phenoxy/phenylthio and substituted versions,
- plus a large “alkyl/alkoxy (1-4C)/(2-4C)” range.
So the landscape competitive pressure is likely on:
- pinning down which specific substitution combinations correspond to actual commercial candidates,
- determining whether those candidates fall into the genus or match exclusions.
3) Methods of use are broad, but still structurally tied to the genus
Even if chemical design-arounds land outside genus coverage, competitors still face:
- method claims tied to “administering a quinazoline derivative of formula I” (and its named dependents in claims 23-29),
- RTK-mediated and RTK sensitive cancer framing.
That means landscape risk is not only compound-level but also:
- whether an at-risk product is a “quinazoline derivative of formula I” as construed.
Enforcement-relevant claim map (quick reference)
Claim coverage types
| Claim number(s) |
Claim category |
What matters for infringement risk |
| 1-6 |
Chemical genus (formula I) |
whether product matches R1/R2/m/n substitutions and not excluded members |
| 7-9 |
Chemical subsets (named compounds) |
ensures coverage for particular embodiments even if genus elements are disputed |
| 10-11 |
Pharmaceutical composition |
same chemical match + formulation coverage |
| 12, 15-21 |
Methods of treatment / anti-cancer / anti-proliferative / RTK inhibition |
whether administered compound is within formula I (or a named dependent compound) |
| 23-29 |
Methods using named compounds |
locks in method coverage for specific embodiments |
Excluded compounds list (high leverage)
| Excluded member |
Appears as excluded in claim 1 (as provided) |
| 4-(4'-hydroxyanilino)-6-methoxyquinazoline |
yes (and hydrochloride salt) |
| 4-(4'-hydroxyanilino)-6,7-methylenedioxyquinazoline |
yes |
| 6-amino-4-(4'-aminoanilino)quinazoline |
yes |
| 4-anilino-6-methylquinazoline |
yes (and hydrochloride salt) |
| 4-anilino-6,7-dimethoxyquinazoline |
yes (and hydrochloride salt) |
What decision-use insights can be drawn from this claim set?
For R&D teams (design and candidate selection)
- The patent is designed to catch broad substitution families around an anilino/quinazoline kinase inhibitor pharmacophore. Candidate designs that only “tweak” R1/R2 within allowed classes remain at risk.
- The explicit exclusions act like “known prior art or known competitors” anchors. Engineering away from the exact excluded structures is a must, but it does not ensure safety because the surrounding genus remains wide.
For IP and portfolio teams (freedom-to-operate and licensing)
- The claim architecture includes both:
- genus chemical claims (hard to evade without full scaffold change), and
- RTK-mediated method claims (hard to evade if the product falls back into the genus).
- If a competitor product is a member of the genus or one of the named embodiments (claims 7, 9, 13, 14, 23-29), enforcement leverage increases because multiple claim categories line up (composition and method).
For investors (probabilistic landscape reading)
- A Markush-style platform claim with extensive substitution ranges suggests:
- broader coverage potential across many downstream analogs, but
- heightened dependency on claim construction and exclusion boundaries.
- The named examples (claims 7-9 and 23-29) function like “likely commercial lead” capture, increasing the chance the most relevant embodiments are inside the issued claim set.
Key Takeaways
- US 5,457,105 claims a broad Markush genus of quinazoline derivatives (formula I) using m = 1-3, n = 1-2, and extensive R1/R2 substitution enumerations plus salts.
- The patent contains explicit exclusion carve-outs for five “anchor” quinazoline members, including multiple anilino/hydroxyanilino methoxy/dimethoxy/methylenedioxy and the hydrochloride forms.
- The claim set expands into pharmaceutical compositions and methods of treating RTK-mediated cancers in warm-blooded animals, including cancer-type lists and RTK inhibition framing.
- Dependent claims name specific compounds and corresponding method embodiments, creating enforceability for both genus-level and exemplar-level products.
FAQs
1) Is US 5,457,105 limited to one compound?
No. Claim 1 defines a large substitution-space genus via R1/R2 Markush-style lists, with named sub-embodiments in claims 7-9 and method-specific exemplars in claims 23-29.
2) What are the most important “design-around” elements in the patent?
The hard exclusion list in claim 1. Any product that matches an excluded compound (including the cited hydrochloride salts where stated) falls outside at least those claim boundaries.
3) Do the method claims require a specific cancer type?
Not in the earliest anti-cancer method claims. Later claims narrow to RTK-sensitive cancers and list multiple cancer types, but all methods still depend on the administered compound being within formula I or within named dependent examples.
4) Can a composition claim be avoided by not prescribing a method?
No. If a product contains the claimed compound in a pharmaceutical composition context, composition claims can be implicated independent of method performance. Conversely, method claims also hinge on the compound identity.
5) What is the practical risk pattern for competitor programs?
Switching substituents within allowed R1/R2 classes may still land inside the genus. Risk reduction typically requires avoiding both the genus structural boundaries and the named exclusions, or using a non-quinazoline scaffold.
References (APA)
[1] United States Patent 5,457,105, “Quinazoline derivatives and pharmaceutical compositions and methods of use,” claims 1-29 (text provided in prompt).
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