Patent: 9,056,110

Summary for Patent: 9,056,110

Title:	Substituted pyrimidinone-phenyl-pyrimidinyl compounds
Abstract:	The present disclosure provides pyrimidinone-phenyl-pyrimidinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and inflammatory disease, having the structure of Formula (I): ##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.
Inventor(s):	Selness; Shaun R. (Chesterfield, MO), Devadas; Balekudru (Chesterfield, MO), Hockerman; Susan L. (Kirkwood, MO), Monahan; Joseph B. (St. Louis, MO)
Assignee:	CONFLUENCE LIFE SCIENCES, INC. (St. Louis, MO)
Application Number:	13/707,326
Patent Claims:	see list of patent claims

United States Patent 9,056,110: Claims, Claim-Value, and US Patent Landscape

US Patent 9,056,110 is a multi-tier chemical patent built around a generic Markush framework (Formula (I)) that narrows through dependent claim chains to enumerated concrete analogs, then expands to broad formulation coverage. The claims are written to capture a large combinatorial space of substituent variants (R1-R5 and multiple aryl/heteroaryl substituents), while the dependent claims anchor enforceability on a small number of specific exemplified structures and stereoisomeric pairs.

What is actually claimed (high-level claim taxonomy)?

The patent includes four core layers:

1. Compound claims (claims 1-24): a generic structure (Formula (I) and related formulae II-V and VI-like sub-structures), narrowed by dependent claim parameter sets, and then directed to specific compound embodiments (claim 12 and others).
2. Stereochemical embodiments (part of claim 12): explicit (+)/(–) pairs are included in the enumerated list.
3. Pharmaceutical compositions (claims 25-47): composition claims covering:
   • monotherapy with the claimed compound (claim 25),
   • combination therapy with a second active ingredient chosen from long lists across therapeutic areas (claims 26-47).
4. Carrier language: standard pharmaceutically acceptable carrier language without additional functional limitations.

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How broad are the compound claims, and where do they narrow in practice?

Claim 1 is broad Markush chemistry with extensive substitution latitude

Claim 1 defines “A compound, or pharmaceutically acceptable salt” of Formula (I) with these main degrees of freedom:

• R1: H, alkyl, halo
• R2: alkyl or alkoxy, optionally substituted by cyclic/aromatic groups (C3-6 cycloalkyl, phenyl, 5/6-membered heterocycle), and those cyclic/aromatic rings can be substituted by a wide “decorating” set (alkyl/alkoxy, alkyl-O-alkyl, hydroxyl/hydroxyalkyl, amido, carboxy, acyl/carbamido, cyano, aminoalkyl, thiolalkyl, halo/haloalkyl).
• R3 and R4: independently H/alkyl/halo
• R5: carbonyl or cyclic/aromatic ring systems, where carbonyl is substituted with an additional group (shown as a structural placeholder) or is “alkynyl”; the cyclic/aromatic ring can be further substituted by the same decorating set.

Practical breadth impact: Claim 1 covers a very large chemical search space. It is not constrained to one target site, one ring system, one substituent class, or one substitution pattern. This type of claim tends to be commercially valuable for infringement coverage but becomes fragile if:

• the specification does not support the breadth with enablement across the full Markush set, or
• prior art exists for the core scaffold plus at least some of the high-probability substitutions.

Dependent claims 2-11 tighten R1-R5 ranges and restrict core aryl/heteroaryl

The tightening is systematic:

• Claim 2 restricts:

  • R1 to H/C1-5 alkyl and specific halogens (bromo, chloro, fluoro),
  • R2 to C1-5 alkoxy with optional substitution via cyclic/aryl rings (or R2 = hydroxyl),
  • R3/R4 to narrower H or C1-5 alkyl and specific halogens,
  • R5 to a 5/6-membered heterocycle substituted within a similar set.

• Claim 3 further restricts:

  • R1 to methyl/ethyl and bromo/chloro,
  • R2 to C1-3 alkoxy (or hydroxyl),
  • R3 and R4 each to narrower allowed sets,
  • R5 to heteroaryl with specified substituent classes.

• Claims 4-11 progressively narrow to a specific “six-membered heteroaryl” placement in claim 5 and then to a restricted set of enumerated heteroaryl ring types in claim 5.

Practical breadth impact: The dependent chain is doing two things:

• reducing enforceability risk by tightening permissible substituents, and
• creating a “last mile” of defined embodiments that can be mapped to competitor analogs.

Claim 12 is the enforceability anchor: a list of concrete compounds

Claim 12 states “Compound of claim 11, selected from the group consisting of:” followed by a long enumerated list of specific structures (including benzyl-oxy substituted, pyrimidinyl substituted, and oxazolyl/thiazolyl substituted variants). It includes both racemate-resolved entries (e.g., “(-)” and “(+)” prefixed analogs) in the list.

What this means in litigation terms:

• If prosecution history or claim construction limits are involved, courts can more confidently treat enumerated structures as supported embodiments.
• Enumerated entries are also useful for mapping competitor products if their structures match.

Claims 6-10 and 13-24 introduce additional formula frames (II-V) that capture closely related structural variants

• Claim 6: “wherein the compound has the structure of Formula (II).” It restricts R1, R3, R4, R20, R50, R51.
• Claim 7-10: specify R20 to “phenyl substituted with” defined sets or a broad list of heteroaryl ring types (thienyl, furyl, imidazolyl, pyrazolyl, oxadiazolyl, triazolyl, pyridyl, pyrazinyl, etc.) with substituent sets.
• Claim 11 then narrows R20 to a further restricted set and adds R50 = methyl and R51 = methyl and/or hydroxyl.
• Claims 13-15 and 16-18 and 19-24 similarly add formula-based constraints and then converge on enumerated structures (claim 15 is a single specific compound).

Practical breadth impact: These additional formula frames reduce “single point of failure” risk. If one Markush reading is attacked, other formula frames can still capture structurally adjacent embodiments.

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How much of the claim set is composition-enforcement versus chemistry-enforcement?

Composition claims 25-47 are broad and cross-therapeutic

Claim 25: pharmaceutical composition comprising therapeutically effective amount of a compound of claim 6 (or salt) and pharmaceutically acceptable carrier.

Claim 26: composition with first API = compound of claim 6 and second API selected from broad therapeutic classes:

• anti-inflammatory drugs,
• anti-neoplastic drugs,
• anti-atherosclerotic drugs,
• drugs for airway tissue hypersensitivity.

Claims 27-47 expand second API lists with named examples.

Strength:

• Combination coverage is extensive. It does not require mechanistic pairing or a specific dosing ratio in the claim language you provided.
• The second API lists include very common blockbuster classes across multiple indications.

Weakness/fragility:

• Composition claims usually require the exact combination of actives. If a competitor uses the same first API (compound of claim 6) but avoids the listed second API actives, composition infringement drops sharply.
• If an accused product markets the first API alone, composition claims become irrelevant.

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Claim-by-claim value: what a competitor would most likely map

Most attractive compound-mapping targets

For competitor structure-to-claim mapping, the most actionable hooks are:

• Claim 12’s enumerated structures: direct literal targets, including stereoisomer-marked members.
• Claim 15’s single explicit compound: strong literal capture if any candidate matches.
• Claims 22-23 and similar near-endpoint dependent claims: narrow R1-R4 and restricted R20 sets.

Most attractive combination-mapping targets

For product-market mapping, the composition layer is the easiest to anticipate:

• If the competitor runs a combination regimen with the claimed first API plus:
  • NSAID set (ibuprofen, naproxen, acetaminophen, aspirin, celecoxib, etc.) (claim 28),
  • TNF-alpha blockers (etanercept, infliximab, adalimumab) (claim 30),
  • statins (atorvastatin, rosuvastatin, etc.) (claim 39),
  • airway tissue hypersensitivity drugs (beta2 agonists, anticholinergics, corticosteroids, PDE inhibitors, leukotriene modulators, methyl xanthines, anti-infectives) (claims 40-47), then the composition claims create a broad infringement net.

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Critical assessment of claim drafting: where patent defensibility is likely strongest or weakest

1) Markush breadth is high; defensibility depends on written description and enablement

Claim 1’s structure is a classic high-combinatorics Markush framework. The patent likely captures many analogs without needing to enumerate each. That improves commercial coverage, but it also increases vulnerability if:

• the specification does not provide adequate support for the full range of “decorating substituents,”
• the biological activity data (if any) does not cover the breadth, or
• a prior-art teaching points to the core scaffold plus the “most likely” substituent patterns.

Enforcement consequence: Even if novelty is established for the broad scaffold, invalidity challenges often focus on the enablement and written description of the full Markush scope.

2) Dependent narrowing to concrete exemplars reduces risk, but does not eliminate it

The existence of:

• an enumerated list in claim 12 and
• a single explicit compound in claim 15 helps show that the applicant could concretely make and define at least part of the claimed space.

Enforcement consequence: In litigation, these embedded exemplars often become the practical “survival path” for claim meaning and evidence.

3) Composition claims are broad on partner drugs, but conditional on combination use

Claims 26-47 include long lists of named actives. That increases the chance that a marketed combination lands inside the claim boundaries.

Enforcement consequence: The best defense for a competitor is often to choose actives not listed, or to position the regimen as not including the claimed first API compound of claim 6.

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US patent landscape: what the landscape implies for freedom to operate (FTO)

What can be asserted from the claim set alone

From the claim text provided, the patent is not a “one-compound, one-use” family. It is a scaffold-based chemistry patent plus combination composition claims. That typically creates a landscape where:

• Competitors making closely related analogs must evaluate literal infringement for the Markush ranges, not just the exact enumerated examples.
• Competitors using combination regimens must evaluate whether their second API is one of the listed actives.

Landscape gaps you should assume

Even without external citation, the claim language itself implies three common landscape pressure points:

1. Core scaffold prior art risk: Generic scaffolds with similar substitution patterns are common in medicinal chemistry; novelty often hinges on specific linkage geometry or substituent placement.
2. Late-stage substitution permutations: The claim includes numerous ring systems and substituent sets; competitors can design around by excluding one required substituent class or altering heteroaryl selection.
3. Combination list risk: Many of the listed second actives are extremely common. If the claimed first API becomes commercially used, many combinations in standard of care could fall inside the claim lists, depending on local/regional label and study design.

What to monitor in prosecution history (critical for landscape interpretation)

Although not provided, prosecution history can critically affect claim interpretation, especially for Markush claim construction. The landscape assessment should therefore treat:

• claim 1 reading expansively or narrowly,
• the definition of Formula (I) and internal structural placeholders,
• and whether the dependent chains constrain breadth enough to avoid prior-art reads

as decisive FTO variables.

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Key Takeaways

1. US 9,056,110 is scaffold-centric with very broad Markush compound coverage at claim 1, followed by systematic dependent narrowing (claims 2-11) and hard enumerated exemplars (notably claim 12 and claim 15).
2. Formula re-framing across claims 6-24 (Formula (II), (III), (IV), (V)) creates multiple claim pathways to capture close analogs, reducing reliance on a single claim interpretation.
3. Composition coverage is broad on combination partners (claims 25-47) and spans multiple drug classes (NSAIDs, TNF-alpha blockers, statins, airway hypersensitivity drugs).
4. For enforcement and FTO mapping, the most actionable targets are claim 12’s listed structures, the specific compound in claim 15, and the named partner drug lists in claims 28-47.

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FAQs

1) What is the most enforceable part of the chemistry claims?

Claim 12 and claim 15 are the highest-confidence enforceability anchors because they list concrete structures rather than relying solely on broad Markush ranges.

2) Does the patent cover salts?

Yes. Claim 1 states “compound, or pharmaceutically acceptable salt.”

3) How do the composition claims expand risk?

Claims 26-47 allow combination use with many named drug actives across multiple therapeutic categories, making infringement more likely if the first API is used in combinations that match the listed partners.

4) Can a competitor avoid infringement by changing only the second active drug?

Yes. If the competitor uses the same first API but pairs it with an unlisted second active (or uses the regimen outside what is claimed), composition infringement can be reduced.

5) Where should FTO work focus first?

Structure mapping against claim 12 / claim 15 exemplars and the endpoint-dependent parameter sets (claims 10-11, 21-23), then product-label mapping for combination partners against claims 28-47.

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References

[1] United States Patent 9,056,110 (claims text provided in prompt).

Details for Patent 9,056,110

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	November 26, 1997	9,056,110	2032-12-06
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	February 19, 2002	9,056,110	2032-12-06
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	August 24, 1998	9,056,110	2032-12-06
Immunex Corporation	ENBREL	etanercept	For Injection	103795	November 02, 1998	9,056,110	2032-12-06
Immunex Corporation	ENBREL	etanercept	For Injection	103795	May 27, 1999	9,056,110	2032-12-06