Patent: 10,137,172

Summary for Patent: 10,137,172

Title:	Administration regime
Abstract:	The invention relates to a novel administration regime useful in the treatment of diseases or conditions where administration of insulin will be of benefit, as well as to kits for use in the same. In particular, the invention relates to a long-acting or ultra-long acting insulin for use in treating a disease or condition where administration of insulin will be of benefit, wherein the administration of said insulin comprises or consists of the following steps: (a) optionally providing a blood sample to be tested from an individual in need of treatment; (b) taking a single fasting blood (or plasma) glucose measurement from said individual in need of treatment; (c) using the single fasting blood (or plasma) glucose measurement to determine the insulin dose to be administered; and (d) administering the long-acting or ultra-long insulin to the individual at the dose determined in step (c).
Inventor(s):	Johansen; Thue (Koebenhavn OE, DK), Francisco; Ann Marie Ocampo (Copenhagen V, DK), Christensen; Torsten (Princeton, NJ), Kongsoe; Jens Harald (Hoersholm, DK), Ahlgreen; Trine (Frederiksberg C, DK)
Assignee:	Novo Nordisk A/S (Bagsvaerd, DK)
Application Number:	14/888,118
Patent Claims:	see list of patent claims

Comprehensive patent-landscape analysis for U.S. Patent 10,137,172 (insulin degludec titration based on single fasting glucose to dose LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin)

U.S. Patent 10,137,172 claims a tight insulin degludec (insulin degludec; LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin) titration protocol for type 2 diabetes that uses (i) one fasting glucose measurement per titration cycle, (ii) discrete dose-step adjustments of ±4 U around defined glucose bands (≤3.9 mmol/L (≤70 mg/dL), 4.0 to 5.0 mmol/L (71 to 90 mg/dL) no change, and ≥5.1 mmol/L (≥91 mg/dL) increase by +4 U), (iii) an administration interval of at least 3 days between titrations, and (iv) HbA1c improvements comparable to protocols using an average of at least three consecutive fasting glucose readings per week. Dependent claim 5 adds combination co-administration with liraglutide. The patent’s practical enforceability hinges on whether accused users/providers follow this specific titration cadence, dosing rule, and glucose-threshold logic when administering degludec in U.S. care settings.

Because you supplied the claim set but not the asserted parties, Orange Book listing, publication number, prosecution history, or the full specification, a complete claim chart and freedom-to-operate conflict mapping across the entire US/WO family cannot be produced from the information provided. What follows is a critical, decision-grade analysis of claim scope and the most important legal and competitive touchpoints implicated by the claim language you provided.

---

What patents protect insulin degludec titration based on fasting glucose single measurement and fixed ±4 U steps?

Answer (claim-scope snapshot): U.S. Patent 10,137,172 protects a specific insulin degludec titration method defined by a single fasting glucose input, glucose band thresholds mapped to fixed ±4 U dose changes, and titration performed with at least a 3-day dosing interval, with clinical performance benchmarked by HbA1c comparability to multi-day-average titration.

Key claim elements that likely define patent coverage

1. Drug/active identity

   • The method requires insulin degludec by its chemical name/description: LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin.

2. Input measurement

   • The titration uses a fasting blood or plasma glucose sample or a non-invasive glucose measurement.
   • The protocol requires a single fasting glucose measurement per titration cycle.

3. Decision logic

   • If measured fasting glucose is ≤70 mg/dL (≤3.9 mmol/L), then reduce dose by 4 U.
   • If 71–90 mg/dL (4.0–5.0 mmol/L), then no change.
   • If ≥91 mg/dL (≥5.1 mmol/L), then increase by 4 U.

4. Timing rule

   • At least 3 days between consecutive titrations (and thus at least 3 days of administration period between dose adjustments).

5. Performance constraint

   • The method requires that comparable HbA1c improvements are seen relative to titration methods based on averaging at least three consecutive fasting glucose measurements per week.

6. Operationalization / repetition

   • Step (d) is repeated by repeating steps (a)–(d).
   • Claim 3 specifies that measurement and dosing can be done on the same day and repeated continuously as needed, with step (d) lasting at least 3 days.

7. Combination therapy limitation (dependent)

   • Claim 5 adds use with liraglutide (concurrently or consecutively).

How enforceability likely turns on “how closely an accused protocol matches the thresholds and cadence”

• A competitor that uses different glucose bands (even if directionally similar), or uses a multi-day average rather than a single measurement, or changes dose by non-±4 U increments, or titrates more frequently than 3 days, creates a meaningful non-infringement argument under a strict reading.
• A provider that titrates with clinician discretion that can override the fixed ±4 U rule may reduce literal infringement risk unless the rule is still followed in substance.

---

How broad is U.S. Patent 10,137,172 claim 1 compared with typical degludec titration regimens?

Answer: Claim 1 is narrower than general degludec “titration” claims because it is defined by a specific decision table (≤70/no-change/≥91 mg/dL) plus fixed ±4 U adjustments plus ≥3-day interval and single fasting measurement.

Comparison to common clinical titration patterns (what matters legally)

Many insulin titration approaches in practice involve:

• Multiple consecutive readings, or
• Different correction magnitudes (for example, 1–2 U steps, weight-based starting rules, or individualized increments), or
• Different timing cadence (daily or every 2 days), or
• Different glucose targets and adjustment rules.

Under U.S. patent claim interpretation, those differences typically matter more than “clinical equivalence” because claim 1 is specific in how glucose is mapped to dose change and when adjustments occur.

Role of “comparable improvements in HbA1c”

The HbA1c comparability clause is not just background. It is a limiting performance requirement in claim 1. Two practical litigation angles follow:

• If the accused method uses the same decision logic and cadence, HbA1c comparability is likely treated as inherent or satisfied based on method performance evidence.
• If the accused method deviates in dosing cadence or glucose measurement logic, it is harder for a patentee to argue that the method meets the HbA1c benchmark even if some short-term glucose metrics improve.

---

What do claims 2–5 add, and where do they narrow infringement risk?

Claim 2: “further comprising repeating steps (a) to (d)”

• Claim 2 does not change the decision logic. It clarifies repetition of the protocol.
• In infringement analysis, this usually functions as belt-and-suspenders reinforcement that the method is iterative, not a one-time titration.

Claim 3: same-day execution and continuous repetition

• Adds an operational framing: steps (a)–(c) can be performed on the same day; insulin administration period is at least 3 days starting same day; steps are repeated continuously as needed.
• This likely targets settings where titration happens daily in name but the dose adjustment decision is made using fasting glucose and then maintained for at least 3 days.

Claim 4: combination with additional diabetes drugs

• Broadens beyond degludec monotherapy but still limits by requiring concurrent or consecutive co-administration with one or more additional diabetes drugs.
• The limitation can increase infringement specificity for combination scenarios, but it also reduces the chance that a monotherapy regimen accidentally infringes a dependent claim.

Claim 5: specifically liraglutide

• This is a further narrowing dependent claim: co-administration with liraglutide (a GLP-1 receptor agonist).
• Enforcement against monotherapy using degludec alone would not reach claim 5 by dependency.

---

What patent landscaping exists around “single fasting glucose titration” for insulin degludec?

Answer: From the claim language alone, U.S. Patent 10,137,172 appears to target a design choice: reducing titration burden by using a single fasting glucose measurement and enforcing a simple fixed-step dose adjustment rule that still yields HbA1c performance comparable to regimens requiring multiple readings.

Adjacent prior art risk areas that typically challenge such claims

A patent landscape around this concept usually clusters into four families of potential relevance:

1. Insulin titration methods using fasting glucose targets

   • Methods with structured fasting targets exist across basal insulins (including degludec or other ultra-long basal insulins).
   • Many differ on the number of readings (single vs average), increment size, and frequency.

2. “Averaged” glucose titration schemes

   • If the closest art averages multiple consecutive fasting readings per week, then the claimed “single measurement” is a distinguishing feature.
   • The HbA1c comparability language in claim 1 implies the patentee expects the record to show that single-measurement performance is at least functionally comparable.

3. Dose adjustment increments and thresholds

   • Fixed ±4 U increments tied to explicit glucose bands is relatively specific. Prior art often uses variable increments or different target ranges.

4. Combination titration with GLP-1 RA (liraglutide)

   • Combination therapy regimens are common in type 2 diabetes. The novelty would lie in the insulin titration protocol used when liraglutide is co-administered, not the existence of the combination itself.

Litigation posture implication

If prior art exists that already discloses a single fasting glucose-based insulin titration with similar thresholds and increments, then claim 1 faces validity risk under anticipation or obviousness. If prior art uses multi-day averages, it more cleanly supports novelty but does not eliminate obviousness risk if a skilled clinician would reasonably simplify averaging without losing clinical effectiveness.

---

When does U.S. Patent 10,137,172 expire, and what does that mean for generic entry timelines?

Answer: Expiration timing requires the patent’s filing date, priority date, and any adjustments or terminal disclaimers. The user-provided prompt does not include those data, so a definitive exclusivity timeline cannot be computed from the claim text alone.

Practical implication for market planning:

• Even if the patent expires later, the protocol is a method-of-treatment claim. Generic “entry” does not automatically avoid infringement if clinicians continue practicing the patented protocol using a generic/biosimilar equivalent of degludec. The key is whether the generic degludec can be launched without inducing infringement, and whether the protocol remains in use.

---

What is the Orange Book status of insulin degludec and how does it intersect with this method patent?

Answer: Orange Book listing details (drug product, NDA/BLA number, listed patents, and listed expiration dates) cannot be determined from the claim set alone.

General intersection logic:

• If U.S. Patent 10,137,172 is listed for the degludec drug product in the Orange Book, Paragraph IV certifications and litigation can shape the launch date of generic degludec products (for which the regulatory pathway would be driven by FDA’s framework for insulins).
• Method-of-treatment patents are typically listed for the NDA/BLA as “method of use” or “therapeutic method” patents; litigation and FDA certifications can still bind launch timing via the regulatory stay provisions where applicable.

---

What generic/biosimilar entry risks exist for insulin degludec given method claims?

Answer: Launch risk depends on (i) whether the patent is listed in the relevant FDA patent list for degludec, and (ii) whether the FDA-regulated product launch triggers an automatic litigation stay via a certified listed patent.

From a method-claim perspective, two distinct risk channels exist:

1. Regulatory/launch channel

   • If degludec generics face a patent-listed barrier and are litigating a listed patent, launch is often delayed.

2. Post-launch practicing-the-protocol channel

   • Even after launch, enforcement against prescribers, clinics, or payer protocols could persist if clinicians follow the claimed titration rules. In practice, enforcement often focuses on incentivized adoption through clinical pathways, patient education materials, or payer standing policies.

---

How strong are the claims legally based on their internal limitations?

Answer: Strength is most likely driven by the specificity of (a) single fasting measurement, (b) exact glucose thresholds (≤70, 71–90, ≥91 mg/dL), (c) fixed ±4 U adjustments, and (d) ≥3-day interval. These internal constraints narrow the claim and can both:

• strengthen non-obviousness/novelty by distinguishing from broader titration concepts, and
• increase vulnerability if a single prior reference discloses the same decision table and timing.

Patentability vulnerabilities to evaluate (using only the provided claim elements)

• Obviousness risk: A court may find it obvious to replace multi-reading averages with one reading to reduce patient burden, if prior art already provides fasting titration with similar targets and adjustments.
• Indefiniteness risk: The glucose bands are clear, and the timing is expressed (“at least 3 days”), so indefiniteness is unlikely to be a major weakness based on claim language.
• Enablement/support risk: The HbA1c comparability requirement implies clinical evidence. If the specification lacks robust support for comparability under the claimed regimen, the claim could face support issues, though the prompt does not include specification content.

---

What formulations are protected by U.S. Patent 10,137,172?

Answer: The claim is not tied to a dosage form (pen vs vial), concentration, or formulation excipient. It is a method claim requiring administration of insulin degludec and follow-on titration logic. Infringement analysis would focus on:

• the administered insulin being insulin degludec, and
• the dosing adjustment rule and timing being followed.

---

What patent litigation affects U.S. Patent 10,137,172?

Answer: Litigation status cannot be stated from the claim text alone. No case caption, court, docket number, or parties were provided.

---

Key Takeaways

• Claim 1 is tightly constrained: single fasting glucose measurement per titration cycle; specific thresholds (≤70/no-change 71–90/≥91 mg/dL); fixed ±4 U insulin degludec adjustments; ≥3 days between titrations; and a HbA1c comparability performance requirement versus averaging ≥3 readings per week.
• Dependent claims narrow further: claim 5 requires liraglutide co-administration.
• Infringement risk pivots on protocol fidelity: deviations in glucose band cutoffs, adjustment magnitude, number of readings, or titration interval are strong non-infringement levers.
• Regulatory launch timing cannot be concluded without the Orange Book listing details and the patent family’s priority/filing dates.

---

FAQs

1. Does U.S. Patent 10,137,172 cover insulin degludec titration when clinicians use a two- or three-day fasting average instead of a single fasting reading?
   The claim language requires a single fasting measurement for the determination in each titration cycle.

2. Can the claimed method be practiced using non-invasive glucose monitoring devices rather than blood/plasma sampling?
   Claim 1 explicitly includes “non-invasive glucose measurement” as an alternative input.

3. Is “at least 3 days” between titrations sufficient if titration is performed every 2 days in practice?
   “At least 3 days” is a limiting requirement; a practice of adjusting every 2 days would not meet the literal timing constraint.

4. If a generic insulin degludec is available, does method-patent coverage persist against clinicians using the same titration logic?
   A generic launch does not eliminate method infringement if clinicians follow the patented protocol using the generic product.

5. Does claim 5 require liraglutide specifically, or does it cover other GLP-1 receptor agonists?
   Claim 5 specifies liraglutide.

---

References (APA)

1. United States Patent 10,137,172. (Claim set provided in user prompt).

Details for Patent 10,137,172

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Novo Nordisk Inc.	TRESIBA	insulin degludec	Injection	203314	September 25, 2015		2034-04-30
Novo Nordisk Inc.	TRESIBA	insulin degludec	Injection	203314	November 21, 2018		2034-04-30