Details for Patent: 8,173,663

Summary for Patent: 8,173,663

Title:	Dipeptidyl peptidase inhibitors
Abstract:	Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising: wherein M is N or CR4; Q1 and Q2 are each independently selected from the group consisting of CO, SO, SO2, and C═NR9; and each L, X, R1, R2, and R3 are as defined herein.
Inventor(s):	Jun Feng, Stephen L. Gwaltney, Jeffrey A. Stafford, Zhiyuan Zhang, Bruce J. Elder, Paul K. Isbester, Grant J. Palmer, Jonathon S. Salsbury, Luckner G. Ulysse
Assignee:	Takeda Pharmaceutical Co Ltd
Application Number:	US11/929,593
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,173,663
Patent Claim Types: see list of patent claims	Use;

United States Patent 8,173,663 (Type I/II Diabetes and Breast Cancer Method Claims): scope, claim architecture, and US patent landscape

US Patent 8,173,663 is a broad US method-of-treatment patent covering administration of a defined small-molecule chemical series (formula-based) to treat type I diabetes, type II diabetes, and breast cancer. Claim scope is driven by (i) a wide combinatorial definition of substituents around a core heterocycle (not fully shown in your excerpt), (ii) a very broad “aryl/heteroaryl” and substitution-permutation framework for R2/R4/R10/R11, and (iii) a constrained but still expansive set of allowed “-L-X” benzylaryl motifs. Dependent claims further narrow by selecting specific R3 (heterocycles or heteroaryl groups) and specific exemplified compounds (claims 25–26) that anchor the broad formula to particular marketed-style lead candidates.

High-level risk read-through: the patent’s enforceability in the US depends on whether an accused product practices the claimed method (direct or induced infringement) and whether the product contains a compound within the asserted formula scope. The claim language you supplied is structured to support infringement even when the accused drug uses salts, stereoisomer mixtures, or single stereoisomers within the defined compound genus.

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What does US Patent 8,173,663 claim: type 1 diabetes, type 2 diabetes, and breast cancer method-of-treatment?

Claim 1, claim 2, and claim 3: the independent method-of-use triad

From your claim text, the independent claims are:

• Claim 1: treating type II diabetes by administering a therapeutically effective amount of a formula-defined compound.
• Claim 2: treating breast cancer by administering a therapeutically effective amount of the same or substantially overlapping formula-defined compound.
• Claim 3: treating type I diabetes by administering the same formula-defined compound.

These are independent method-of-treatment claims. They are not formulation claims, not manufacturing claims, and not composition claims. They are written for direct infringement through administration and prescribing/using guidance.

Core structure: the claims define a compound genus, not a single active

All three independent claims are limited to compounds defined by a complex formula with substituents:

• Q1 and Q2 are each CO (implies a carbonyl-containing moiety, consistent with a dione-like motif in your later dependent definitions).
• R2 is hydrogen or a large set of alkyl/cycloalkyl/aryl/heteroaryl substituents, each substituted or unsubstituted.
• R3 comprises a second substructure described in the omitted “formula wherein R3 comprises the formula” text, later narrowed through dependent claims listing specific heterocycles/heteroaryls and specific “amine-containing” heterocycles.
• R4 is hydrogen or an extensive set of substituents (halo, perhaloalkyl, cyano, thio, alkyl/cycloalkyl/heterocycloalkyl, aryl/heteroaryl, carbonyl-group substituents, etc.).
• R10 and R11 are independently selected from an extensive substituent group, or taken together to form a 4-, 5-, 6-, or 7-membered ring.
• “L-X taken together” is selected from a long list of substituted or unsubstituted benzylaryl motifs of the form —(CH2)-(substituted phenyl) with many allowed substitutions (cyano, hydroxy, alkenyl, alkynyl, methoxy, nitro, carboxy, carboxamido, sulfonamido, tetrazolyl, aminomethyl, hydroxymethyl, phenyl substituents, halo patterns, fluoro-chloro-bromo variants, trifluoro/difluoro patterns, etc.; plus heterocycloalkyl-substituted phenyl variants).

Why the formula language matters for scope

Your supplied claim language is a classic genus claim built from:

1. broad substituent “choose-from” groups, and
2. a controlled linker-aromatic tail (“-L-X”) where the tail is constrained to the listed phenyl variants, with specific hetero substituents and halo patterns.

The result is broad capture of a structural series even if an accused compound differs at many positions, so long as it remains within the allowed genus definitions.

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How broad is the compound genus in US Patent 8,173,663 (R2, R4, R3, R10/R11, and -L-X limits)?

R2 scope: very broad

In claims 1–3, R2 is:

• hydrogen
• or a wide set: C1-10 alkyl; C3-12 cycloalkyl and cycloalkyl(C1-5)alkyl; hetero(C3-12)cycloalkyl and hetero(C3-12)cycloalkyl(C1-5)alkyl; aryl(C1-10)alkyl; heteroaryl(C1-5)alkyl; bicycloaryl variants; carbonyl/thiocarbonyl/sulfonyl/sulfinyl/imino/amino; aryl, heteroaryl; and hydroxy/alkoxy/aryloxy/heteroaryloxy; and groups can be substituted or unsubstituted.

Dependent claims then narrow R2:

• Claim 20: “R2 is a substituted or unsubstituted (C1-10)alkyl”
• Claim 21: “R2 is a substituted or unsubstituted (C1-4)alkyl”
• Claim 22 and Claim 23/24: additional more detailed linker structures (“R2 is —Y—Z… and Z is hydrogen or selected…”; or R2 defined by a more specific intermediate template with A/B/t and variable R18/R24)

R4 scope: broad aryl/alkyl substitution including cyano and halo

Claim 1–3 define R4 similarly broadly:

• hydrogen or
• halo/perhalo(C1-10)alkyl, amino, cyano, thio
• C1-10 alkyl, cycloalkyl, heterocycloalkyl
• arylalkyl, heteroarylalkyl
• aryl, heteroaryl
• carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl
• sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl
• imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy
• carbonyl group, imino group, sulfonyl group, sulfinyl group.

R10/R11 scope: substitution or ring-closure

R10 and R11 are independently selected from the same broad sets, or together form a 4-, 5-, 6-, or 7-membered ring. This supports both:

• flexible substitution on a dialkyl/dialkyl-like motif, and
• structural diversification by ring closure.

R3 scope: (i) heterocycle/heteroaryl platform and (ii) basic nitrogen functionality

Independent claims say “R3 comprises the formula,” which your dependent claims then clarify by limiting R3 to:

• heterocycloalkyl (Claim 4)
• heteroaryl (Claim 5)
• basic nitrogen-containing heterocycles/heteroaryls and explicit examples (Claims 6–19, 15–18, 19).

Key limitation: multiple dependent claims tie R3 to a basic nitrogen capable of interacting with a carboxylic acid side chain of an active site residue of a protein (Claims 7, 15). Claim 15–18 narrows spacing (1–5 atoms) and whether the nitrogen is in a ring.

“-L-X” scope: long but controlled aromatic tail list

The “-L-X taken together is selected from the group consisting of —(CH2)-(substituted phenyl) …” list is the most concrete boundary in your excerpt.

Your list includes, at the phenyl ring:

• cyano at 2 or 3 positions (with benzyl CH2)
• hydroxy at 2 or 3
• alkenyl at 2 or 3
• alkynyl at 2 or 3
• methoxy at 2 or 3
• nitro at 2 or 3
• carboxy at 2 or 3
• carboxamido at 2 or 3
• sulfonamido at 2 or 3
• tetrazolyl at 2 or 3
• aminomethyl at 2 or 3
• hydroxymethyl at 2 or 3
• phenyl substituent at 2 or 3
• halo at 2 or 3
• amide CONH2 at 2 or 3
• CONH(C1-7)alkyl at 2 or 3
• CO2(C1-7)alkyl at 2 or 3
• NH2 at 2 or 3
• (C3-7)alkyl at 2 or 3
• (C3-7)cycloalkyl at 2 or 3
• aryl at 2 or 3
• heteroaryl at 2 or 3
• heterocycloalkyl at 2 or 3
• explicit halo/fluoro/cyano/difluoro/trifluoro patterns, including:
  • 2-bromo-5-fluoro
  • 2-chloro-5-fluoro
  • 2-cyano-5-fluoro
  • 2,5-dichloro; 2,5-difluoro; 2,5-dibromo
  • 2-bromo-3,5-difluoro; 2-chloro-3,5-difluoro
  • 2,3,5-trifluoro; 2,3,5,6-tetrafluoro
  • 2-bromo-3,5,6-trifluoro; 2-chloro-3,5,6-trifluoro
  • 2-cyano-3,5-difluoro; 2-cyano-3,5,6-trifluoro.

This list supports a defensible argument that the patent captures a specific benzyl-phenyl substitution pattern space, not any benzylphenyl tail.

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What dependent claim narrowing is used (basic nitrogen, heterocycles, stereochemistry, and R2 linkers)?

R3 narrowing: explicit heterocycles and amines

Claims 13–19 provide a detailed R3 boundary:

• Claim 13: examples of heteroaryl groups including furan, thiophene, pyrrole, pyrazole, triazole, isoxazole/oxazole, thiazole/isothiazole, oxadiazole, multiple pyridines and diazines, triazines, benzofuran, benzothiophene, imidazole/benzimidazole, indole/isoindole, quinoline/isoquinoline, cinnoline, quinazoline, naphthyridine, pyridopyridine, quinoxaline, phthalazine, benzothiazole.
• Claims 14–18: require R3 substituents that provide basic N and define separation distance (1–5 atoms) and whether the nitrogen is part of the heterocycle/heteroaryl ring.
• Claim 19: enumerates explicit amino-substituted ring systems:
  • “3-amino-piperidinyl-1-yl”
  • “3-aminomethyl-pyrrolidin-1-yl”
  • “3-aminoazetidin-1-yl”
  • “3-amino-3-methylpiperidin-1-yl”
  • “3 aminohexahydroazepin-1-yl”
  • “piperazin-1-yl”
  • “homopiperazin-1-yl”
  • “3-amino-pyrrolidin-1-yl”
  • and related “R-3…” variants.

R2 narrowing: alkyl and linker-forming template

• Claim 20–21 restrict R2 to C1–10 alkyl and C1–4 alkyl.
• Claim 22 introduces an explicit template: R2 is —Y—Z with Y a linker giving 1,2, or 3 atom separation; atoms in the linker are C/O/N/S; Z is hydrogen or one of the broad substituent sets.
• Claim 23 and 24 further constrain R2 by templates with:
  • A=S/O/NR24, B=CR23/N; R23 variable; R24 variable.
  • t is 0–5 and R18 variable selected from halo/perhaloalkyl/CF3/alkyl/alkenyl/alkynyl/aryl/heteroaryl/aminosulfonyl/alkylsulfonyl/aryl/heteroarylsulfonyl/aryloxy/heteroaryloxy/arylalkyl/heteroarylalkyl/cycloalkyl/heterocycloalkyl/amino/thio/cyano/nitro/hydroxy/alkoxy/carbonyl/imino/sulfonyl/sulfinyl.

Salt and stereochemistry: explicit claim support

• Claim 27: compound can be a pharmaceutically acceptable salt.
• Claim 28: compound can be a mixture of stereoisomers.
• Claim 29: compound can comprise a single stereoisomer.

This increases enforceability against generics because typical ANDA practice often uses salts and stereochem variants unless the generic product uses a non-infringing structure.

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Which specific compounds are “exemplified” in US Patent 8,173,663 (claims 25–26) and what does that do to claim strength?

Claims 25 and 26 list specific compound species in addition to the broad genus formula. That list is legally important because it:

• identifies a set of species that clearly fall inside the genus as drafted, and
• provides concrete anchors for claim construction when disputes arise over whether a specific accused molecule meets the generic formula limits.

Species list in claim 25 (partial reproduction from your excerpt)

The compounds listed include multiple “benzonnitrile” and “pyrimidine-2,4-dione” derivatives and several variants with:

• amino-piperidinyl substituents
• stereochemical tags (R / (±))
• halogen patterns on the benzyl substituent
• cyano-, fluoro-, chloro-, bromo-substituted benzyl tails
• additional carboxy methyl ester / carboxylic acid forms
• thiophene analogs
• benzoimidazole substituent tails
• pyrazol-1-yl benzyl tails
• pyrrol-1-yl benzyl tails.

Species list in claim 26 (subset focused on R stereochemistry)

Claim 26 repeats a subset, focusing on (R)-Amino-piperidinyl stereochemistry and related analogs.

Practical implication for enforcement

When claim construction is contested, courts often look to:

• dependent claims
• definitions
• exemplified compounds to resolve ambiguity in broad formula language. Because claims 25–26 explicitly enumerate multiple benzyl-cyano/halo and basic-amine-containing analogs, the patent’s genus boundaries likely have less interpretive drift than generic “formula” patents that omit examples.

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What patent estate issues arise: is this only one US patent, or part of a broader family?

Your prompt is restricted to US Patent 8,173,663 and the claims text you provided. Without the patent’s bibliographic record (publication number, filing dates, priority claims), no accurate family mapping, expiration computation, or related-continuation assessment can be produced from your excerpt alone.

No additional, complete and accurate landscape can be asserted without those records.

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How does this patent typically relate to FDA Orange Book, generics, and Paragraph IV?

No Orange Book listing, listed drug product, NDA/ANDA number, or regulatory filing date is provided in your prompt. A correct Orange Book and Paragraph IV analysis requires:

• the specific NDA/ANDA referencing this patent,
• listed patent expiration date(s),
• exclusivity or regulatory exclusivity periods,
• Orange Book “patent type” (drug substance, drug product, method-of-use, etc.),
• and any litigation/settlement docket data tied to that listing.

Those facts are not present in your input.

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What is the most likely infringement theory and design-around path for competitors?

Infringement theory

Given the claims are method-of-treatment claims:

• infringement typically arises when a clinician prescribes and administers the claimed compound for the claimed disease indication (type I/II diabetes or breast cancer).
• induced infringement theories can apply if a manufacturer provides instructions or promotional materials that encourage use for those indications.

Design-around vectors

The strongest practical “escape hatches” are structural non-overlap with the claim’s compound genus limits:

• removing the allowed —(CH2)-X benzyl tail variants outside the enumerated “-L-X” list, or
• changing the R3 amine functionality such that it no longer matches the “R3 comprises the formula” genus limitations (and especially the nitrogen/basic heterocycle constraints in dependent claims), or
• using a fundamentally different compound class that does not satisfy the core formula variables (Q1/Q2 dione motif, R2/R4/R10/R11 templates).

Salt/stereoisomer variants are explicitly captured by dependent claims 27–29, so avoiding infringement by simply changing salt form or stereochemical purity is less effective if the core structure remains within the genus.

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Key claim-scope takeaways for business decisions

1. Indication coverage is explicit and broad: type I diabetes, type II diabetes, and breast cancer are all independent claim endpoints.
2. Compound coverage is genus-level: R2/R4/R10/R11 definitions are wide; R3 is narrowed in dependent claims to heterocycles/heteroaryls with basic N functionality; the “-L-X” tail is constrained by an enumerated list of benzyl-phenyl substitution patterns.
3. Salt and stereochemistry don’t narrow the patent’s practical reach: claim 27–29 absorb common product variations.
4. Exemplified species reduce interpretive slack: claims 25–26 list numerous concrete analogs that fit the broad formula, which tends to strengthen infringement/claim-construction arguments against close structural variants.

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Key Takeaways

• US 8,173,663 is a method-of-treatment patent covering administration of a defined small-molecule series for type I/II diabetes and breast cancer.
• Claim scope is built from broad substituent permutations plus a controlled benzyl-phenyl tail (“-L-X”) list and amine-containing heterocycle/heteroaryl (R3) functionality supported by detailed dependent claims.
• Salt and stereochemical form are expressly within scope, increasing risk for generic or follow-on developers.
• Competitive risk hinges on whether an accused product’s active ingredient falls within the asserted compound genus and whether its clinical use is directed to the claimed indications.

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FAQs

1) Does US 8,173,663 protect only the active ingredient, or the dosing/indication?
It protects the method of treating specific conditions (type I diabetes, type II diabetes, breast cancer) by administering a therapeutically effective amount of a compound defined by the formula.

2) Can a competitor avoid the patent by using a different salt form?
Claim 27 includes pharmaceutically acceptable salts, so salt-form changes alone do not necessarily avoid infringement if the compound remains within the claimed formula.

3) Does the patent cover stereoisomer mixtures and single stereoisomer products?
Yes. Claims 28–29 include both mixtures of stereoisomers and single stereoisomers.

4) What claim element is likely the tightest boundary: R2, R4, R3, or the benzyl tail (“-L-X”)?
In your excerpt, the “-L-X” benzyl tail appears as the most concrete, enumerated limitation, while R2/R4/R10/R11 are broad templates and R3 is narrowed through dependent heterocycle/amine-related definitions.

5) Which dependent claims are most important for designing around basic-nitrogen R3 features?
Claims 7, 15–18, and 19 focus on a basic nitrogen interacting with a protein carboxyl side chain, including distance (1–5 atoms) and whether the nitrogen is a ring atom, plus explicit amino-heterocycle examples.

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References (APA)

1. United States Patent No. 8,173,663. (claims text as provided in user prompt).

Drugs Protected by US Patent 8,173,663

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 8,173,663

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1586571		C300640	Netherlands
European Patent Office	1586571		CA 2014 00011	Denmark
European Patent Office	1586571		PA2014011	Lithuania
European Patent Office	1586571		14C0013	France
European Patent Office	1586571		172 5006-2014	Slovakia
European Patent Office	1586571		C20140007 00126	Estonia