Details for Patent: 10,343,995

Summary for Patent: 10,343,995

Title:	Biphenyl compounds useful as muscarinic receptor antagonists
Abstract:	This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, s, t, W, Ar1, R1, R2, R3, R4, R6, R7, and R8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
Inventor(s):	Mathai Mammen, YuHua Ji, YongQi Mu, Craig Husfeld, Li Li
Assignee:	Theravance Biopharma R&D IP LLC
Application Number:	US16/130,076
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

Patent 10,343,995 Landscape: Scope, Claims, and US Expiry Risk for Inhaled Bronchodilation with Biphenyl-2-ylcarbamic Acid Ester

US Patent 10,343,995 covers inhaled bronchodilation using a specific small-molecule active (the named biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, including salts), dosed to deliver ~10 to 200 μg/day and formulated for aqueous nebulizer delivery (including pH and buffer constraints) and optionally co-administered with a β2-agonist and/or steroidal anti-inflammatory.

Key takeaways (commercial and legal): the patent’s claim scope is anchored on (1) the exact active identity, (2) a narrow inhaled daily dose window, and (3) a method-of-treatment via inhalation with nebulizer and single daily dose options. Dependent claim structure adds formulation constraints (aqueous carrier, isotonic solution, pH 3 to 8, specific buffer type) and combination therapy elements. Design-around is most feasible by changing either dose delivered/day, route/device (non-nebulizer inhalation), formulation (non-aqueous or non-isotonic or pH outside range), or avoiding inclusion of the specific buffer and isotonic conditions where relevant to dependent claims.

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How broad is US Patent 10,343,995 claim scope for inhaled bronchodilation?

Direct answer: The independent claims (1 and 13 in the provided set) are method claims covering administering a pharmaceutical composition containing the specific active and delivering about 10 μg/day to about 200 μg/day to produce bronchodilation in a mammal/human. Breadth is limited by the active’s identity and the day-level dose delivery range. The claim set then narrows via dependent limitations: inhalation, nebulizer, single daily dose, and specific aqueous/isotonic/pH/buffer formulation parameters, plus optional combination therapies.

What the independent claim requires (Claims 1 and 13)

Both independent claims share the same core elements:

1. Method for producing bronchodilation

   • Claim 1: “a mammal”
   • Claim 13: “a human patient”

2. Administration of a pharmaceutical composition
   The composition must contain:

   • a pharmaceutically acceptable carrier, and
   • the named biphenyl-2-ylcarbamic acid ester (or a pharmaceutically acceptable salt)

3. Dose delivery constraint is tied to daily amount

   • about 10 μg/day to about 200 μg/day of the active (or its salt)

4. Administration is the operative act
   The claims do not require manufacturing steps; they require dosing instructions that result in bronchodilation.

Practical implication

Because the independent claims are framed as “administering… in an amount sufficient to provide about X μg/day to about Y μg/day,” infringement analysis will typically turn on:

• whether the product’s delivered dose to the patient fits the 10–200 μg/day band, and
• whether the administered composition contains the same specific active (or salt).

How dependent claims narrow the scope

The dependent claims add optional narrowing constraints that can create multiple infringement “entry points” depending on the accused product label, formulation, and delivery device.

• Route/device narrowing
  • Claim 2: inhalation
  • Claim 3: nebulizer inhaler
• Dosing regimen narrowing
  • Claim 4: single daily dose
  • Claim 15 mirrors this for human method
• Carrier/formulation constraints
  • Claims 5, 13, 16: pharmaceutically acceptable aqueous carrier
  • Claim 6 / 17: pH 3 to 8
  • Claims 7–9 / 18–21: further buffer and isotonic aqueous solution
  • Claim 8 / 19: buffer is sodium chloride citric acid buffer
• Combination therapy options
  • Claim 11 / 22: optionally includes β2 adrenergic receptor agonist
  • Claim 12 / 23: optionally includes steroidal anti-inflammatory agent

Practical implication

A competitor can avoid dependent-claim coverage by adjusting:

• device category (non-nebulizer inhalation),
• dosing schedule (not single daily),
• aqueous vs non-aqueous formulation,
• pH outside 3–8 for the aqueous composition,
• buffer composition (not sodium chloride citric acid),
• isotonic conditions,
• combination co-formulation status.

But the independent claims still remain enforceable unless those changes also escape the independent constraints (active identity + 10–200 μg/day delivered + bronchodilation method).

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What active ingredient is claimed in US 10,343,995 and how does that drive infringement?

Direct answer: The claims are specific to the molecule defined as:

“biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester”
and its pharmaceutically acceptable salts.

Why “identity of the active” is the main gate

For composition-based or method-of-use claims framed around administration of “a pharmaceutical composition comprising… [the active],” infringement hinges on whether the accused product contains:

• the same chemical entity, or
• a covered salt (if the salts are defined as pharmaceutically acceptable and covered by the claim language).

If an accused product uses:

• a different ester position,
• a different substituent on the benzoyl/piperidine scaffold,
• a different prodrug,
• or a structurally distinct derivative,

then the independent claims are not met, regardless of device/formulation.

How salts affect scope

The claims explicitly include pharmaceutically acceptable salts of the active. That expands the scope beyond a free base/acid to salt forms that meet “pharmaceutically acceptable” criteria.

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What dose range (10–200 μg/day) is actually claimed and what generic entry risk does it create?

Direct answer: The key independent constraint is delivery of about 10 μg/day to about 200 μg/day of the active (or salt).

How dose-range claims are typically evaluated

In litigation or patent validity challenges, dose-range claims are often evaluated by:

• the accused product’s labeled dosing instructions,
• pharmacokinetic/pharmacodynamic studies translated to “delivered” daily exposure,
• and whether the effective dose to the patient falls within the “about” range.

The “about” qualifier typically provides some leeway around exact numerical endpoints, but it still creates a quantitative boundary for design-around.

Launch scenario sensitivity

• A once-daily product at a delivered daily dose slightly below ~10 μg/day can attempt to fall outside the range.
• A once-daily product above ~200 μg/day can do the same.
• But if the active dose is adjustable in practice (multiple dose strengths, titration), the risk increases because any strength used “in the amount sufficient to provide” the covered band can trigger method claims.

Key design-around levers anchored to the dose claim

• Use a different daily delivered dose (label and actual instruction).
• Avoid “sufficient to provide” in the covered band in intended use instructions.
• If multiple strengths exist, isolate the strength(s) used for the bronchodilation indication outside the band.

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Does the patent cover nebulizer inhalation and single daily dose specifically?

Direct answer: Yes. Dependent claims include:

• inhalation (Claim 2 / 14),
• nebulizer inhaler (Claim 3 / 14),
• and single daily dose (Claim 4 / 15).

Why this matters commercially

Many inhaled bronchodilator products compete in device categories:

• dry powder inhalers (DPIs),
• metered-dose inhalers (MDIs),
• soft mist inhalers,
• nebulizers.

This patent’s dependent claims align with nebulizer inhalation, so competitors using DPIs/MDIs may argue fewer dependent-claim hooks if their route/device is outside “nebulizer inhaler.”

But the independent claims are not limited to nebulizers

Even if dependent claims are avoided, infringement can still occur if:

• the accused product is used for inhalation producing bronchodilation, and
• the active identity and 10–200 μg/day delivery are met.

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What formulation claims are included (aqueous, pH 3–8, isotonic, sodium chloride citric acid buffer)?

Direct answer: Dependent claims constrain the pharmaceutical composition’s properties when it uses an aqueous carrier, including:

• pH 3 to 8,
• buffer is sodium chloride citric acid buffer,
• isotonic aqueous solution,
• and claimed active concentration within the formulation: 0.05 μg/mL to 10 mg/mL.

Formulation scope mapping by claim cluster

Aqueous carrier

• Claim 5 (mammal) / 16 (human): “pharmaceutically acceptable aqueous carrier”

pH range

• Claim 6 / 17: pH 3–8

Buffer identity

• Claim 7 / 18: composition further comprises a buffer
• Claim 8 / 19: buffer is sodium chloride citric acid buffer

Isotonic aqueous solution

• Claim 9 / 20: isotonic aqueous solution

Active concentration range

• Claim 10 / 21: isotonic aqueous solution comprises about 0.05 μg/mL to about 10 mg/mL active (or salt)

Design-around anchored to formulation

A non-infringing formulation strategy can aim at avoiding multiple dependent-claim limitations simultaneously:

• switch from isotonic to non-isotonic formulation,
• change buffer system away from sodium chloride citric acid,
• shift aqueous pH outside 3–8,
• move to a non-aqueous carrier if the independent claims can be met (note: independent claims don’t require aqueous, but dependent claims do).

Manufacturing/IP barrier implication

If a licensed partner needs to keep device and dose constant while altering buffer/pH/isotonic status, the operational burden is non-trivial:

• pH and buffer system affect solubility, stability, and nebulizer performance,
• isotonicity affects tonicity and patient tolerance,
• and concentration windows can affect dosing volume and delivered daily amount.

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What combination therapy is covered: β2 adrenergic agonist and steroidal anti-inflammatory?

Direct answer: The claims permit (as dependent options) combination regimens where the bronchodilation method uses a composition that further comprises:

• a β2 adrenergic receptor agonist (Claim 11 / 22), and/or
• a steroidal anti-inflammatory agent (Claim 12 / 23).

How combination-dependent claims affect infringement

Because these are dependent clauses (“further comprises”), infringement of these dependent claims requires the accused product’s administered composition to include the listed co-ingredients.

Commercially, combination products are common in COPD/asthma care. The presence of β2 agonists or inhaled corticosteroids in the same formulation increases the risk of dependent claim capture if all other independent requirements are met.

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What patents likely sit around US 10,343,995 in the landscape (and why that matters)?

Direct answer: The claim set you provided is structured as a method-of-use + formulation + combination estate. In practice, the active identity and its salts typically have upstream coverage in:

• composition of matter (active molecule and salts),
• prodrug/salt polymorphs,
• intermediates and processes.

Because the patent you specified is US 10,343,995, the relevant landscape analysis usually hinges on whether there are:

1. earlier composition-of-matter patents for the same active,
2. additional formulation patents for nebulizer solutions, pH, isotonicity, and buffers,
3. additional use patents for bronchodilation, asthma/COPD sub-populations, or dosing regimens,
4. and whether any continuations expanded claim sets around dose windows or device routes.

However, without the patent’s full bibliographic data (publication number, title, assignee, priority dates) and without linked patents from the family, a complete US landscape cannot be enumerated from the claims alone.

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How long does US 10,343,995 likely remain enforceable, and when does exclusivity end?

Direct answer: No enforceability timeline can be calculated from the provided claim text alone.

A correct expiration and exclusivity schedule requires at least:

• the patent’s earliest priority date,
• any patent term adjustment (PTA) or terminal disclaimers,
• and any related FDA exclusivity periods tied to the first approved product containing the same active.

This analysis cannot be produced accurately from the claim list provided.

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What Orange Book status and FDA regulatory milestones affect entry timing for inhaled bronchodilators?

Direct answer: Orange Book status, listed patents, and any relevant FDA regulatory exclusivity cannot be determined from the claim text alone.

To map generic/biosimilar entry risk, the analysis typically depends on:

• the NDA/ANDA product listing,
• whether the listed patents include 10,343,995,
• and whether the active is covered as listed for specific strengths/routes.

This information is not available in the input.

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How strong is the patent estate for 10,343,995 based on claim architecture?

Direct answer: The patent has moderate-to-strong enforceability characteristics for three reasons embedded in claim architecture, assuming infringement facts match the independent requirements:

1. Hard chemical identity anchor: coverage tracks the exact active name and salt language.
2. Quantitative daily dose window: reduces the number of design-arounds that keep the same active and similar inhaled dosing.
3. Multiple dependent narrowing hooks: formulation and device/dosing regimens create several plausible infringement pathways when a product resembles nebulized aqueous once-daily dosing.

Where the strength can weaken

• If competitors use alternative delivery devices and/or dosing outside the 10–200 μg/day band, independent claim capture drops.
• If competitors use the same active but formulations are engineered around pH/isotonicity/buffer type, dependent claims may be avoided.

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What generic or competitor entry risks exist if a product uses the same active?

Direct answer: If a competitor markets an inhaled bronchodilator that contains the same active (or a covered salt), a product is at elevated risk of method-of-use infringement when:

• it is used for bronchodilation in patients (as labeled and marketed),
• the intended dose results in delivery “about 10 μg/day to about 200 μg/day,” and
• the product uses nebulizer inhalation and/or aqueous isotonic solutions with pH 3–8 and sodium chloride/citric acid buffer.

Risk is lower when:

• dose delivered is clearly outside 10–200 μg/day,
• device is not a nebulizer inhaler, and
• formulation does not meet the aqueous pH/buffer/isotonic dependent limitations.

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Key Takeaways

• US Patent 10,343,995 is a method-of-use patent for inhaled bronchodilation using a specific active molecule and optional salt forms.
• The independent claims are bounded by the daily dose delivered: about 10–200 μg/day.
• Dependent claims add coverage for:
  • nebulizer inhaler use,
  • single daily dosing,
  • aqueous formulation with pH 3–8,
  • sodium chloride citric acid buffer,
  • isotonic aqueous solutions,
  • and optional combinations with β2 adrenergic agonists and/or steroidal anti-inflammatory agents.
• Design-around is most plausible by changing (a) daily delivered dose band, (b) device category, and (c) formulation characteristics tied to the dependent claims.

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FAQs

1. Does US 10,343,995 require nebulizer use to infringe?
No. Nebulizer language is in dependent claims. Independent claims cover inhalation method use tied to the active and the 10–200 μg/day delivery window.

2. If a competitor uses the same active but a different daily dose, is infringement avoided?
If the daily delivered amount is outside about 10–200 μg/day, the independent dose element is not met, reducing infringement risk.

3. Can a non-aqueous formulation avoid coverage?
Dependent claims require an aqueous carrier and, in further dependents, pH/buffer/isotonic constraints. A non-aqueous formulation can avoid those dependent limitations, though independent claims may still apply if the dose and active identity are met.

4. Do combination products with β2 agonists automatically infringe?
Only if the accused product also satisfies the independent requirements (active identity, daily dose window, bronchodilation method). The β2 agonist coverage is in dependent claims.

5. Does the patent cover isotonicity and specific buffers in every case?
No. Isotonicity and sodium chloride citric acid buffer are dependent claim limitations, so they matter when the formulation matches those features and the independent claims are met.

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References (APA)

1. United States Patent No. 10,343,995.

Drugs Protected by US Patent 10,343,995

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 10,343,995

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	048032
Argentina	104444
Austria	E395335