Details for Patent: 8,691,847

Summary for Patent: 8,691,847

Title:	Benzamides and related inhibitors of factor Xa
Abstract:	Novel benzamide compounds including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating coagulation disorders.
Inventor(s):	Bing-Yan Zhu, Penglie Zhang, Lingyan Wang, Wenrong Huang, Erick A. Goldman, Wenhao Li, Jingmei Zuckett, Yonghong Song, Robert M. Scarborough
Assignee:	Millennium Pharmaceuticals Inc
Application Number:	US13/612,597
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 8,691,847 Scope, Claims, and U.S. Patent Landscape for Thrombosis-Targeting Compounds

US Patent 8,691,847 is a small-molecule IP family built around a “formula compound” core, with claim coverage that expands into (i) chemical variants defined by specific substituent constraints, (ii) pharmaceutical compositions, and (iii) method-of-use claims for preventing or treating “undesired thrombosis.” The independent claim structure is modular: claim 1 establishes the broadest formula-class coverage, dependent claims add parameter constraints, and claims 3–6 and 8–11 add composition and use coverage that can support licensing and generic/biosimilar-style risk analysis via Orange Book style listings (where applicable) and Paragraph IV-style challenges (where applicable).

Key takeaways on claim scope

• Chemical Markush core: the claims are constrained by a specific set of allowed substituents for R1a, R1d1, R1d3, R1e, and a defined A-Q substituent/heterocycle/wiring set.
• Therapeutic use is broad: “preventing or treating…undesired thrombosis” is not limited to a specific patient population, route, dosing regimen, thrombus type, or anticoagulant class mechanism in the claim language you provided.
• Composition coverage is standard: claim 3 (and 4, 8, 10, 11) protect a pharmaceutical composition with a therapeutically effective amount of the claimed compound plus a pharmaceutically acceptable carrier.
• Method claims are administration-based: claims 5–6 and 9 (and claim 11 via composition reference) are “administering” claims, which can matter for infringement theory and design-around strategy.

Because patent-number-only context is insufficient to produce an accurate, complete “landscape” (family members, expiration dates, prosecution history, assignment chain, licensing/IV litigation, and FDA/Orange Book status) without the full patent record, this analysis stays strictly on the claim scope implied by your claim text and the typical legal/technical implications of the claim architecture.

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What is the claim structure of US Patent 8,691,847 and how broad is the formula coverage?

Featured snippet answer: Claim 1 covers a specific Markush-defined chemical scaffold where five substitution sites are limited to discrete allowed groups, with the additional A-Q variable defining the core binding portion; it is then extended to compositions and thrombosis treatment methods.

Independent claims: chemical definition first, then use and formulation

From your claim set, the claim architecture is:

• Claim 1: “A compound of the formula …” with constraints on R1a, R1d1, R1d3, R1e, and A-Q.
• Claim 7: repeats coverage for “a compound of the formula” (your text suggests a broader or differently parameterized formula depiction than claim 1; the text you provided does not include the full substructure drawings/definitions for the formula blocks).
• Claims 3–4: compositions containing compounds of claims 1–2.
• Claims 5–6: thrombosis prevention/treatment methods using compounds of claims 1–2.
• Claims 8–11: composition and method claims using compounds of claim 7 (and a specific formula block referenced in claim 10, with claim 11 tied to the composition of claim 10).

Where the claim scope actually comes from: enumerated substituents

Your claim 1 constraints:

• R1a: H or —F
• R1d1: H or —OCH3
• R1d3: H, —F, —Cl, —Br, —OCH3, —OCF3
• R1e: H, —F, —Cl, —Br
• A-Q: selected from two “or” options (your text shows a structural selection but does not include the two structural options explicitly in text form)

This is a classic “limited Markush” scope profile. The chemical space is enumerated at each site rather than being fully open-ended. That has two practical consequences:

1. Infringement depends on exact substitution inclusion: an accused compound must match the allowed groups at each defined position and match one of the permitted A-Q structures.
2. Design-around can be targeted: swapping a substituent to a group outside the enumerated set (even if chemically similar) can fall outside literal scope.

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How many distinct compound variants does claim 1 cover based on R-group enumerations?

Featured snippet answer: Based on the enumerations explicitly stated for R1a, R1d1, R1d3, and R1e, claim 1 supports at least (2 × 2 × 6 × 4 = 96) substitution patterns before multiplying by the number of A-Q options.

• R1a: 2 options (H, F)
• R1d1: 2 options (H, OCH3)
• R1d3: 6 options (H, F, Cl, Br, OCH3, OCF3)
• R1e: 4 options (H, F, Cl, Br)

Subtotal: 96 combinations.
Then A-Q is “selected from the group consisting of … or …” in your excerpt, which indicates 2 candidate A-Q options, giving up to 192 distinct literal substitution patterns at the level of those variables.

This count is not a definitive inventory of “covered compounds” because:

• your excerpt omits the full definition of each A-Q structural option (could encode additional degrees of freedom),
• the formula block may include other fixed moieties not variable here,
• claims 2 and 7 appear to define additional/alternative formula constraints not fully shown in text.

Still, for infringement screening, the enumeration count provides a concrete starting point for “literal match” filtering.

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What does claim 2 likely do relative to claim 1, and how does it affect freedom-to-operate?

Claim 2 is referenced in claims 4 and 6, but the excerpt does not include claim 2 text. The practical inference from claim numbering is:

• Claim 1 is the independent chemical definition.
• Claim 2 is a dependent claim that further restricts at least one variable or defines a specific A-Q variant, substitution pattern, stereochemistry, or salt form.

For freedom-to-operate (FTO) style analysis, the risk posture is usually:

• A generic or competitor compound may still infringe claim 1 even if it does not infringe the more specific dependent claim 2.
• Therefore, for design-around, the key is matching failure at any required enumerated position in claim 1, not merely bypassing claim 2.

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Which drug-like products are protected: compounds, salts, and pharmaceutical compositions under the claims?

Salts are explicitly within scope

Your text includes “or a pharmaceutically acceptable salt thereof” across the formula claims. That typically broadens coverage beyond the free base/form of the core compound.

Composition claims are broad and carrier-based

Claim 3/4/8/10 provide:

• “A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound…”

These are composition-by-ingredient claims. They generally cover:

• dosage forms that include the specified compound and a carrier excipient system, unless the carrier requirement is operationally limited by dependent limitations (not shown in your excerpt).

Practical implication: If a competitor product contains a literal-claim compound (or its salt) at therapeutic dose, the composition claim is a primary infringement vector regardless of differences in excipient selection.

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What method-of-use claims exist for thrombosis and what are their key limitations?

Core use definition is non-specific

Claims 5–6 and 9 state:

• “preventing or treating a condition in a mammal … characterized by undesired thrombosis”
• “administering … a therapeutically effective amount” of claim 1/2 (and claim 7 in claim 9).

Key features:

• No explicit thrombus subtype (arterial vs venous), no specific clotting factor target, no mention of platelet inhibition vs coagulation cascade inhibition in the excerpt.
• No explicit patient subgroup (e.g., post-op, atrial fibrillation, DVT/PE, ACS).
• No route limitation shown (oral, IV, SC), implying route flexibility unless the full spec restricts administration in a way that might affect doctrine-of-equivalents arguments.

Method claims can be triggered by labeling and clinical use

In litigation, method-of-use infringement is often pursued based on:

• prescribed use,
• promotional materials that induce administration for the claimed thrombosis condition,
• and sometimes on the ANDA label carve-outs.

Your excerpt does not include any “kit” or “dosage regimen” limitation, which is consistent with broad use claims that are easier to map to real-world medical practice.

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How does claim scope split between claim 1 and claim 7? Are they redundant or complementary?

Claim 7 is “A compound of the formula or a pharmaceutically acceptable salt thereof.” Without the actual textual variable definitions for claim 7 (your excerpt shows a formula block but does not show the R-group enumerations), two possibilities exist:

1. Claim 7 is a second independent formula definition that captures a different subset or alternative scaffold.
2. Claim 7 is a repackaging of claim 1 with different variable assignment or a shorthand for the same scaffold.

In either scenario, for an infringement-screening process:

• Treat both claim 1 and claim 7 as potential independent chemical coverage.
• Map candidate compounds against both claim variable definitions; avoid assuming redundancy from claim numbering alone.

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What is the likely functional patent estate structure behind US 8,691,847?

Even without the full family list, the claim set implies a standard estate pattern:

• Core compound claims (formula Markush, including salts)
• Composition claims (carrier + effective amount)
• Method claims (thrombosis treatment/prevention via administration)

This structure is designed to:

• block both “drug substance” manufacturing and “drug product” formulation,
• and extend protection into “use” claims even if alternative formulations are developed.

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What design-around strategies follow directly from the enumerated R-group constraints?

Literal infringement avoidance

To avoid claim 1 literal coverage, a competitor compound needs at least one mismatch versus the enumerated sets:

• Replace R1a with a group other than H or F.
• Replace R1d1 with a group other than H or OCH3.
• Replace R1d3 with a group outside {H, F, Cl, Br, OCH3, OCF3}.
• Replace R1e with a group outside {H, F, Cl, Br}.
• Use A-Q structures not in the permitted “group consisting of” options.

Salt strategy

If a competitor uses a different salt form, claim coverage still likely captures “pharmaceutically acceptable salts,” limiting salt-only workarounds.

Formulation strategy

Because composition claims are “carrier + therapeutically effective amount,” changing excipients generally does not avoid infringement if the active drug substance falls inside the chemical claims.

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How does the thrombosis wording affect “generic entry risk” and litigation posture?

“Undesired thrombosis” is broad. In a typical Orange Book / Hatch-Waxman pathway, broad method claims can increase the probability that:

• a proposed generic’s intended use label or physician prescribing aligns with the claimed use, and
• the innovator will assert method-of-use claims alongside compound/composition claims, depending on listing coverage.

If a product is approved for thrombosis indications, the method claims become central in infringement analyses because the “administering” language matches clinical usage patterns.

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US 8,691,847: What claims are most important for enforcement?

Ranked by enforcement leverage:

1. Claim 1 (compound): direct coverage of drug substance and salts.
2. Claims 3–4 and 8–10 (composition): blocks formulation products containing the same active compound.
3. Claims 5–6 and 9 (method): adds use-based infringement leverage tied to clinical practice and labeling.

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Key Takeaways

• US 8,691,847 is built around a Markush formula claim with enumerated substitution sites. Claim 1 supports up to 96 substitution-pattern combinations across R1a/R1d1/R1d3/R1e, and up to ~192 when accounting for the two A-Q structural options shown in your excerpt.
• The claims extend beyond drug substance into pharmaceutical compositions and method-of-use claims for undesired thrombosis with therapeutically effective administration.
• Literal design-around is most feasible by breaking any enumerated substituent requirement (R1a, R1d1, R1d3, R1e) or using a non-permitted A-Q structure.
• Broad thrombosis wording increases the likelihood that method claims align with real-world prescribing and labeling, strengthening enforcement options.

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FAQs

1) Does US 8,691,847 protect only the free base or also salts?

Your excerpt explicitly includes “pharmaceutically acceptable salt,” so salts are within scope of the formula claims and downstream composition/method claims tied to those compounds.

2) Can a different excipient or dosage form avoid infringement of the composition claims?

If the active compound (or its salt) falls within the chemical claims, composition claims framed as “carrier + therapeutically effective amount” generally remain implicated despite excipient changes.

3) How do the enumerated R-group options change the infringement analysis?

Infringement turns on literal match to the allowed sets at each site (R1a, R1d1, R1d3, R1e) and to one of the permitted A-Q options. Substituting a group outside the enumerated list can avoid literal coverage.

4) What is the scope of the thrombosis method claims in practice?

The claims cover administering for preventing or treating “undesired thrombosis” in a mammal without the excerpted limitations specifying thrombus subtype, mechanism, or route.

5) Is claim 7 an independent chemical coverage trigger or a restatement?

Based on your excerpt, claim 7 is a separate formula claim, but the detailed variable definitions are not provided in text form here. For risk mapping, both claim 1 and claim 7 should be treated as independently testable claim triggers.

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References

No sources were provided or cited in the user prompt, and no patent-document text beyond the claims excerpt was supplied.

Drugs Protected by US Patent 8,691,847

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 8,691,847

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	311366
Austria	412629
Australia	4535301
Australia	5078301
Australia	7486600
Australia	7486700
Australia	780787