Patent: 10,029,011

Summary for Patent: 10,029,011

Title:	Pharmaceutical composition comprising a GLP-1 agonist, an insulin and methionine
Abstract:	A liquid composition comprising a GLP-1 agonist or/and a pharmacologically tolerable salt thereof, an insulin or/and a pharmacologically tolerable salt thereof, and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin where appropriate.
Inventor(s):	Hagendorf; Annika (Frankfurt am Main, DE), Hauck; Gerrit (Frankfurt am Main, DE), Mueller; Werner (Frankfurt am Main, DE), Schoettle; Isabell (Frankfurt am Main, DE), Siefke-Henzler; Verena (Frankfurt am Main, DE), Tertsch; Katrin (Frankfurt am Main, DE)
Assignee:	SANOFI-AVENTIS DEUTSCHLAND GMBH (Frankfurt am Main, DE)
Application Number:	13/509,542
Patent Claims:	see list of patent claims

Executive summary: US Patent 10,029,011 is directed to a specific low-volume aqueous injectable composition containing desPro^36-exendin-4(1-39)-Lys^6-NH2 at ~0.025 to 0.1 mg/mL with insulin glargine (~3.64 mg/mL), methionine (3.0 mg/mL), m-cresol (2.7 mg/mL), 85% glycerol (20.0 mg/mL), zinc chloride (0.06 mg/mL), no added buffer substances, and an acidic pH of 3.5 to 4.5. The patent’s enforceable value is likely concentrated in (i) the exact composition parameters (including “no buffer substances” and the pH window) and (ii) the stability-related functional limitations (6-month chemical/physical integrity; ≥80% unchanged active after 6 months at 25°C; ≤1% oxidized content after 1 month). The risk for challengers is that the claim scope is narrow and composition-specific, but the litigation and competitive landscape depend on whether later products or filings match the same excipient system and pH without buffer, and whether prior art or earlier patents show a materially overlapping formulation of desPro^36-exendin-4(1-39)-Lys^6-NH2 with insulin glargine under similar pH and preservative/excipient conditions.

US Patent 10,029,011 claims analysis: what exact composition is protected?

Core claim (Claim 1) protection target: a combination injectable aqueous liquid with a defined set of components per 1 mL plus a specific pH regime and a “no buffer substances” limitation.

What does Claim 1 require (element-by-element)?

Claim 1 is strict and cumulative. A product must meet all listed constituents and conditions:

• Active 1 (GLP-1 analog): about 0.025 mg to 0.1 mg desPro^36-exendin-4(1-39)-Lys^6-NH2 (or a pharmacologically tolerable salt).
• Active 2 (basal insulin): about 3.64 mg insulin glargine (or a tolerable salt).
• Stabilizer/amino acid: about 3.0 mg methionine.
• Preservative/antimicrobial: about 2.7 mg m-cresol.
• Humectant/viscosity modifier: about 20.0 mg of 85% glycerol.
• Metalloprotein stabilization/complexation component: about 0.06 mg zinc chloride.
• Water: quantity sufficient to make ~1 mL total volume.
• pH constraint: pH 3.5 to 4.5.
• Buffer restriction: “comprises no buffer substances.”
• Implicit formulation context: injectable, aqueous liquid.

Claims 2 to 6: stability performance limits

These add enforceability via measurable stability outcomes at 25°C for 6 months:

• Claim 2: “chemical integrity after storage for 6 months at +25°C.”
• Claim 3: “physical integrity after storage for 6 months at +25°C.”
• Claim 5: at least 80% active ingredients are substantially chemically unchanged after 6 months at 25°C.
• Claim 6: at least 80% active ingredients are substantially physically unchanged after 6 months at 25°C.

Claim 8 adds a degradation-specific metric:

• Claim 8: oxidized content ≤ ~1% after 1 month of storage.

Claims 4, 7, 9: intended use and narrower sub-features

• Claim 4: suitable for parenteral injectable composition.
• Claim 7: pH is exactly 4.5 (a narrower embodiment inside the 3.5 to 4.5 range).
• Claim 9: “pharmacologically tolerable” is included as an explicit limitation.

Critical claim-construction pressure points

For freedom-to-operate and litigation strength, the enforceability often hinges on what counts as meeting each limitation:

1. “No buffer substances”

   • If a competitor uses any buffering agent that is characterized as a buffer under pharmacopeial or formulation science norms, they could argue non-infringement.
   • Many insulin products rely on acidic pH adjustments; some formulations use buffers (e.g., phosphate/citrate) in other contexts. This claim’s “no buffers” language can be a meaningful differentiator.

2. pH range and exact pH (Claim 7)

   • pH drift under conditions, measurement method, and how pH is controlled during manufacturing can create infringement or validity issues.
   • A competitor targeting pH outside 3.5 to 4.5 can design around Claim 1’s pH limitation.

3. Component specificity (m-cresol, methionine, glycerol 85%, zinc chloride)

   • Even if a competitor matches the actives, changing excipients (e.g., replacing m-cresol with another preservative, changing glycerol grade, or using different metal ions) can avoid literal infringement.

4. Stability limitations (Claims 2/3/5/6/8)

   • These can be powerful in litigation if the patentee can show performance data.
   • They also create a practical defense: a challenger can argue that the prior art either inherently meets these stability outcomes or that the claimed stability is not novel over known formulations. The burden shifts on whether the patent provides sufficient evidence and whether prior art disclosure is enabling.

How strong is the patent estate for US 10,029,011: what makes it enforceable?

Strength drivers:

• The claim is composition-dense and not a high-level genus claim. That usually narrows infringement but improves the argument that the patentee identified a specific, nonobvious formulation problem (stability/compatibility of desPro^36-exendin-4(1-39)-Lys^6-NH2 with insulin glargine under acidic, buffer-free conditions).
• The “no buffer substances” plus specific excipient selection can reduce the number of plausible anticipatory formulations in prior art.

Key vulnerability drivers:

• Combination patents often face validity pressure if prior art discloses overlapping excipient systems for insulin glargine with acidic pH and preservatives (m-cresol) and known stabilizers (methionine) plus zinc. If a prior reference already teaches the insulin portion, and separately teaches the GLP-1 analog formulation at similar pH with overlapping excipients, an obviousness attack can combine teachings.
• Stability metrics can be attacked for routine optimization or as an inherent property of overlapping formulations.

Which patents protect desPro36-exendin-4(1-39)-Lys6-NH2 plus insulin glargine combinations?

Without the complete bibliographic record and the patent’s own family context (publication numbers, priority dates, and related continuations), only limited, claim-derived landscape conclusions can be made from the information provided. A complete patent landscape requires the patent’s full text (including specification examples), prosecution history, and family members. The analysis below therefore focuses on claim-driven protection categories that typically appear in estates around GLP-1 analog + insulin coformulations.

Landscape clusters typically relevant to this combination

1. GLP-1 analog formulation patents

   • Typically cover aqueous solutions, preservatives (m-cresol or phenolic compounds), amino acid stabilizers (methionine), and pH/tonicity ranges.

2. Insulin glargine formulation patents

   • Typically cover acidic pH, glycerol, zinc content, phenolic preservatives, and stabilization against aggregation and deamidation.

3. Coformulation compatibility patents

   • Typically cover the compatibility window where insulin glargine and GLP-1 analogs do not cause unacceptable degradation or precipitation, including specific pH and “buffer-free” or specific buffer choices.

4. Method-of-use patents

   • Not asserted by Claim 1 as written, but often in the same families: dosing regimens for diabetes management, titration, and combinations.

Where US 10,029,011 is likely positioned

Based on Claim 1, US 10,029,011 is likely a formulation/composition patent. Enforceable scope will track the specific excipient and pH package rather than a broad “any mixture of insulin and GLP-1.”

When does US 10,029,011 lose exclusivity: expiration timeline and term constraints

A precise expiration date cannot be computed from the claims alone. Expiration depends on:

• earliest effective filing (priority),
• patent term adjustment/extension (if any),
• terminal disclaimer,
• and whether continuation practice affected term.

Because no bibliographic data (filing date, priority date, PTA/PTE) is provided here, a specific expiration date cannot be produced without risking incorrectness.

What Orange Book status exists for US 10,029,011?

Orange Book status requires:

• the specific NDA/BLA and listed patents,
• and linkage codes for drug substance and drug product.

US 10,029,011’s Orange Book listing cannot be asserted from the claims alone because the relevant product identity (the marketed or application-linked drug) is not supplied.

Paragraph IV challenges: what generic entry risks exist if a coformulation goes off-patent?

Paragraph IV is relevant only if the listed patent is Orange Book-listed for an ANDA product. Without the Orange Book listing and the drug product identity, a credible claim-by-claim Paragraph IV risk assessment cannot be made.

How does this formulation compare with known insulin glargine baselines?

Claim 1’s excipient choices are strongly aligned with insulin glargine formulation conventions:

• m-cresol as preservative,
• glycerol as tonicity/viscosity component,
• zinc chloride as part of insulin glargine structure stabilization,
• acidic pH (3.5 to 4.5),
• and no added buffers.

The novelty, if any, is in combining that insulin glargine excipient/pH framework with desPro^36-exendin-4(1-39)-Lys^6-NH2 at a defined dose range and demonstrating chemical/physical stability and low oxidation.

What prior art might anticipate or render obvious this claim?

A complete prior art analysis requires the specification’s description of the problem, the examples, and the filing dates versus publication dates. However, the claim structure suggests likely prior art vectors:

Anticipation pathways (strict)

An anticipation reference would need to disclose, in a single document:

• the same GLP-1 analog (desPro^36-exendin-4(1-39)-Lys^6-NH2),
• insulin glargine at ~3.64 mg/mL,
• methionine 3.0 mg/mL,
• m-cresol 2.7 mg/mL,
• 85% glycerol 20 mg/mL,
• zinc chloride 0.06 mg,
• pH 3.5 to 4.5,
• and explicitly no buffer substances,
• plus the resulting stability metrics (at least inherently disclosed or explicitly tested).

This is a high bar for literal anticipation, making validity challenges more likely to focus on obviousness.

Obviousness pathways (combination)

An obviousness case often combines:

• prior art describing insulin glargine aqueous solutions with the same excipient system and acidic pH,
• prior art describing formulation of a GLP-1 analog (or a close analog) in acidic, buffer-free or compatible solutions with similar preservatives/stabilizers,
• and then argues routine optimization to set the pH and excipient ratios to achieve acceptable stability.

Claims 2/3/5/6/8 could serve as rebuttal evidence for nonobviousness if the patent demonstrates unexpected stability or improved chemical integrity versus the expected outcome.

How to assess infringement risk for a competing coformulation

Literal infringement checklist

A competing product/formulation must match Claim 1’s parameter stack:

• concentration range for desPro^36-exendin-4(1-39)-Lys^6-NH2: 0.025 to 0.1 mg/mL,
• insulin glargine about 3.64 mg/mL,
• methionine 3.0 mg/mL,
• m-cresol 2.7 mg/mL,
• 85% glycerol 20 mg/mL,
• zinc chloride 0.06 mg/mL,
• water to 1 mL,
• pH 3.5 to 4.5,
• and no buffer substances,
• with parenteral suitability and tolerable salt scope.

Design-around levers

• move pH outside 3.5 to 4.5,
• include a buffering agent (if it can be characterized as a “buffer substance”),
• substitute m-cresol,
• substitute zinc source or omit zinc,
• alter glycerol grade or amount,
• or alter desPro^36-exendin-4 dose outside 0.025 to 0.1 mg/mL.

Stability-claim testing risk

Even if a competitor aligns the excipients, they can avoid infringement on the stability-related claims (2/3/5/6/8) if stability is materially worse than required thresholds. Conversely, the patentee can rely on stability data to prove performance.

Litigation and settlement impact: what patent disputes affect commercialization?

No litigation docket or settlement record can be tied to US 10,029,011 from the claims alone. Without the patent’s case history, the competitive impact cannot be quantified.

Key Takeaways

• US 10,029,011 Claim 1 is a narrow, excipient-and-pH-defined composition claim: desPro^36-exendin-4(1-39)-Lys^6-NH2 combined with insulin glargine in an aqueous, acidic (pH 3.5 to 4.5), buffer-free formulation containing methionine, m-cresol, 85% glycerol, and zinc chloride at specified milligram-per-mL levels.
• Claims 2, 3, 5, 6, and 8 add enforceability through stability performance at 25°C for 6 months and an oxidation cap after 1 month.
• Patent strength is likely highest where competitors attempt to match the exact excipient/pH/buffer-free package; the “no buffer substances” limitation is a key design-around lever.
• A defensible expiration date, Orange Book linkage, Paragraph IV risk, and litigation impact cannot be produced from the claim text alone.

FAQs

1. What does “no buffer substances” mean for insulin + GLP-1 coformulations in patent terms?
2. If a competitor matches the excipient concentrations but uses a different pH target, does it avoid US 10,029,011?
3. How do Claims 2/3/5/6 (25°C, 6 months, ≥80% unchanged actives) affect an infringement strategy?
4. What formulation changes most effectively reduce the likelihood of meeting oxidation limits like Claim 8?
5. How should a freedom-to-operate team map stability testing data to the patent’s “chemical” vs “physical” integrity requirements?

References

1. Provided claims text for US Patent 10,029,011 (user-supplied).

Details for Patent 10,029,011

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Sanofi-aventis U.s. Llc	LANTUS	insulin glargine	Injection	021081	April 20, 2000		2030-11-11
Sanofi-aventis U.s. Llc	LANTUS	insulin glargine	Injection	021081	April 25, 2007		2030-11-11
Eli Lilly And Company	BASAGLAR	insulin glargine	Injection	205692	December 16, 2015		2030-11-11