Patent: 10,485,851

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Summary for Patent: 10,485,851

Title:	Compositions in the form of an injectable aqueous solution comprising human glucagon and a co-polyamino acid
Abstract:	An injectable aqueous solution, the pH of which is from 6.0 to 8.0, having at least: a) human glucagon, and b) a co-polyamino acid bearing carboxylate charges and hydrophobic radicals Hy. In an embodiment, the compositions have, in addition, a gastrointestinal hormone.
Inventor(s):	Geissler; Alexandre (Lyons, FR), Laage; Segolene (Lyons, FR), Charvet; Richard (Rillieux la Pape, FR), Soula; Olivier (Meyzieu, FR), Duracher; David (Lyons, FR), Meiffren; Gregory (Meyzieu, FR)
Assignee:	ADOCIA (Lyons, FR)
Application Number:	15/616,627
Patent Claims:	see list of patent claims

United States Patent 10,485,851: What the Claims Actually Cover and Where the Patent Landscape Traps Competitors

US Patent 10,485,851 claims an injectable, aqueous, near-neutral (pH 6.0 to 8.0) formulation of human glucagon combined with a specific class of glucagon-associated amphiphilic polyamino acid conjugates (a glutamic/aspartic copolyamino acid bearing carboxylate charges and covalently attached hydrophobic radicals Hy), plus optional excipients (polyanions, zinc salts, and even GLP-1 / “gastrointestinal hormones”). Claim 1 is the backbone: it defines the chemical architecture of the polymer-drug conjugate and the formulation window, then narrows ranges via dependent claims.

From an infringement and freedom-to-operate (FTO) standpoint, the landscape risk is not “glucagon + polymer.” It is glucagon + a very specific covalent polymer structure (formulas I to IV and II/II’/III/III’) under tight compositional parameters (pH, stoichiometry of hydrophobic substitution, polymer DP, and concentration windows), delivered as an injectable aqueous solution.

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What Does Claim 1 Require for Coverage?

Core formulation parameters

Claim 1 requires all of the following:

• Dosage form / medium
  • “Injectable aqueous solution”
• pH window
  • 6.0 to 8.0
• Actives
  • Human glucagon
  • A co-polyamino acid consisting of:
  • Glutamic or aspartic units bearing carboxylate charges
  • Hydrophobic radicals Hy attached to the copolyamino acid
• Counterion
  • Free acid functions are present as alkaline cation salts: Na+ or K+
• Polymer substitution density constraint
  • Ratio i = (number of hydrophobic radicals)/(number of glutamic or aspartic units) satisfies:
  • 0 < i ≤ 0.5
• Polymer chain length
  • Degree of polymerization (DP) in glutamic/aspartic units: 10 to 250
• Hydrophobic radical count vs glucagon stoichiometry
  • Dependent claim 11 adds: [hydrophobic radical]/[human glucagon] < 15 (but Claim 1 itself does not add this ratio)

The hydrophobic radical architecture is formula-driven

Claim 1 defines Hy as a radical of Formula I, with structural variables governed by GpR, GpA, GpC, a, b, p, c, d, r and attachment sites indicated by “*”.

• Attachment-mode switch (r)
  • If r = 0: Hy is bound via a carbonyl of Hy to N-terminal nitrogen of the copolyamino acid, forming an amide.
  • If r = 1: Hy is bound via an amide formed from an amine function of Hy precursor and an acid function on the copolyamino acid, or equivalently via carbonyl of Hy to N-terminal nitrogen depending on which precursor functional group reacts.
• Side-chain options inside Hy
  • GpR is a divalent alkyl fragment with specific carbon counts depending on whether GpR is from Formula II or II’.
  • GpA is a C1 to C6 alkyl
  • GpC is a monovalent alkyl fragment where x depends on p:
  • if p = 1: x = 11 to 25
  • if p = 2: x = 9 to 15
• Additional terminal functionality on GpR-containing options
  • GpR-linked radical definitions include:
  • divalent alkyl with one or more –CONH2 functions, and
  • an unsubstituted ether or polyether segment (4 to 14 C and 1 to 5 O atoms)

What Claim 1 forces on “injectability” and “near-neutral stability”

The claim does not say “stability,” but the pH window 6.0 to 8.0 is a functional constraint that maps to:

• glucagon aggregation and deamidation sensitivity to pH,
• and polymer ionization/solubility behavior for carboxylate copolymers.

This matters because competitors cannot simply change excipients. To design around, they must generally either:

• move outside the pH window (or avoid being “aqueous solution” in the way the claim is construed), or
• use a different polymer class that does not satisfy the explicit formula-driven Hy attachment and composition ranges, or
• avoid the required polymer substitution parameters.

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How Dependent Claims Narrow the Chemical Space

Claims 2 and 3: specific Hy regimes

• Claim 2: Hy selected from Formula I with p = 1, recited as Formula V
• Claim 3: Hy selected from Formula I with a = 1 and p = 2, recited as Formula VI

This matters for design-around: if a competitor uses a polymer with the “wrong” p regime (or wrong combination of a/p), it may evade the dependent claim scope even if it falls within Claim 1’s broad Hy language. Claim 1 still remains the broadest threat.

Claims 4 through 8: copolyamino acid selection is also formula-limited

• Claim 4: polymer is selected from copolyamino acids of Formula VII with defined units:
  • D is aspartic unit (–CH2–) or glutamic unit (–CH2–CH2–)
  • DP “n+m” is 5 ≤ n+m ≤ 250 (this appears inconsistent with Claim 1’s DP 10–250, but the dependent claim creates additional constraints)
• It also defines which fragments can sit at R1 and R2, and again ties Hy to formulas I/V/VI with r=1 or r=0 options.
• Claims 5 to 8:
  • Claim 5: a subset where n = 0 (a particular architecture of VIIb)
  • Claim 6: subset where R2 is Hy with r=1 and GpR of Formula II’
  • Claim 7: subset where D is aspartic only
  • Claim 8: subset where D is glutamic only

These dependent claims substantially reduce the “workable” design space if a competitor is trying to build a close alternative polymer.

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Formulation Quantities and Ratio Constraints

Concentration windows

• Claim 9: polymer concentration ≤ 40 mg/mL
• Claim 10: human glucagon concentration 0.25 to 5 mg/mL

These are not mere processing preferences. For infringement, the claimed composition must fall within these ranges.

Hydrophobic radical-to-glucagon molar ratio

• Claim 11:
  • molar ratio [hydrophobic radical]/[human glucagon] < 15 If a competitor increases polymer coverage per glucagon beyond that threshold, they can try to argue non-infringement (though Claim 1 itself is broader and could still be alleged to cover if ratio requirements are not construed as implicit).

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Optional Additives: Claims 12 to 16 Expand Use-Case Coverage

Polyanion and zinc salt

• Claim 12: includes a polyanionic compound
• Claim 13: includes a zinc salt

These features can matter in actual product development because zinc can affect glucagon aggregation and polymer interactions. If a market formulation uses zinc and a polyanion, the patent’s optionality language can catch additional embodiments.

Gastrointestinal hormones (GLP-1 family)

• Claim 14: includes a gastrointestinal hormone
• Claim 15: selects from: exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, analogs/derivatives/salts
• Claim 16: gastrointestinal hormone concentration 0.01 to 10 mg/mL

This is a major landscape feature: it expands the claim’s practical application beyond “glucagon-only” products to combination drug formats. Competitors developing co-formulations must ensure they do not accidentally satisfy the polymer architecture and also fall within the additive concentration range.

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Critical Claim Construction Pressure Points for the Landscape

1) The claim is structurally demanding: Hy is not “any hydrophobe”

Most formulation patents about glucagon-polymer combinations use functional descriptors (solubilizers, stabilizers). Here, Hy is constrained by explicit chemical formulas and parameterized attachment sites.

Landscape implication: generic “surfactant-like” or “PEGylated” approaches may still miss the claim if they do not recreate the formula-defined Hy radicals and amide linkage mode(s) bound to the copolyamino acid.

2) The polymer backbone is constrained to glutamic/aspartic units with carboxylate charges

A competitor using lysine, acidic acrylic polymers, maleic anhydride copolymers, or neutral polyethers will usually fail Claim 1’s copolyamino acid definition unless the polymer is demonstrably within the defined copolyamino acid structure.

3) pH is an explicit hard boundary

The pH window 6.0 to 8.0 is a clean non-infringement handle if design can move outside it without losing injectability.

4) Stoichiometry and DP create additional “numerical design” constraints

• DP 10 to 250 (Claim 1)
• i ≤ 0.5 substitution density
• polymer concentration ≤ 40 mg/mL
• glucagon concentration 0.25 to 5 mg/mL
• hydrophobic-to-glucagon molar ratio < 15 (Claim 11)

These create a “three-layer” fencing: chemical, parameter, and formulation.

5) Optional additives can broaden infringement for real-world products

If a competitor’s product uses zinc salts or polyanions, the optional nature of Claims 12-13 may still capture them if the composition meets Claim 1 and the dependent claim elements are present. Same for GLP-1 family co-formulations under Claim 14-16.

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Patent Landscape Analysis: Where the Real Competitive Risk Lies

Without full bibliographic details (filing dates, assignees, and the complete claim set of the family members), only the landscape dynamics that flow directly from the claim scope can be stated with certainty. The risk pattern is still clear:

A. The landscape is likely crowded around “glucagon stabilization for injection”

Glucagon has a long history of formulation patents addressing:

• aggregation control,
• solubilization,
• viscosity/modifiers,
• pH buffers,
• and co-solutes.

However, US 10,485,851 differentiates itself by tying stabilization to a specific covalently attached amphiphilic poly(glutamate/aspartate) system.

Competitive implication: many “glucagon + polymer” patents may be non-overlapping if they do not match the structural Hy formulas and the defined substitution/DP parameters.

B. The landscape risk concentrates on polymer-drug conjugate vendors and formulation method developers

If any earlier patents disclosed:

• amphiphilic glutamate/aspartate copolymers with covalent hydrophobe attachment,
• near-neutral pH injectable solutions,
• and explicit coupling chemistries producing amide-linked hydrophobes to N-terminal/precursor-derived groups, then US 10,485,851 likely faces:
• prior art anticipation risk for the claimed polymer class,
• obviousness risk if the combination of known polymer architecture and known glucagon stabilization was routine.

But the claim’s formula detail is a strong filter: prior art must match the specific Hy formula family and parameter regimes (p values, radical length limits, ether/amide motifs, i and DP windows).

C. Combination therapy adds another infringement vector

Claim 14-16 can collide with combination product patents or co-formulation patents (glucagon with GLP-1 mimetics). Many combination patents address:

• simultaneous administration,
• or co-formulation using conventional excipients.

The differentiator is that this patent requires the specific glucagon + specialized copolyamino acid system. So infringement risk expands only where the combination product uses a polymer within the claim.

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What Competitors Should Do If They Want a Clean Design-Around

Design-around levers directly mapped to claim elements:

1. Move pH outside 6.0 to 8.0
2. Use a polymer backbone not limited to glutamic/aspartic units with carboxylate charges
3. Change hydrophobe conjugation chemistry so it does not match r=0/r=1 amide linkage definitions tied to the specified N-terminal or precursor-derived mechanisms
4. Use hydrophobic moieties that do not match Hy formula I and its sub-classes (V and VI)
5. Violate numeric ranges
   • polymer concentration > 40 mg/mL or
   • glucagon concentration outside 0.25 to 5 mg/mL or
   • hydrophobic radical/glucagon molar ratio ≥ 15
6. For combination products, avoid GLP-1 family molecules defined in Claim 15 or move the hormone concentration outside 0.01 to 10 mg/mL

These are the only clean non-infringement handles that follow from the claim text.

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Key Takeaways

• US 10,485,851 is a formulation patent anchored to a formula-defined amphiphilic poly(glutamate/aspartate) system with amide-linked hydrophobe radicals Hy.
• Claim 1’s coverage depends on (i) pH 6.0 to 8.0, (ii) injectable aqueous solution, (iii) human glucagon, (iv) the copolyamino acid’s structural Hy formulas (I and II/II’/III/III’ definitions), (v) i ≤ 0.5 and DP 10 to 250, and (vi) Na+ or K+ counterions.
• Dependent claims tighten Hy sub-classes and polymer architectures (Claims 2-8) and add measurable formulation constraints (Claims 9-11).
• Claims 12-16 expand the threat envelope into zinc/polyanion formulations and glucagon + GLP-1 mimetic co-formulations with defined concentration ranges.
• The main landscape differentiation is structural exactness: many “glucagon stabilization” patents may be non-overlapping if they do not replicate the defined Hy/polymer architecture.

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FAQs

1) What is the single most important claim element for infringement risk?

The claim’s requirement that the copolyamino acid bears hydrophobic radicals Hy defined by Formula I (with r-linked amide attachment) and the specific sub-definitions II/II’/III/III’. Many alternatives will fail because they do not reproduce that structural family.

2) Does the patent cover any polymer excipient that stabilizes glucagon at neutral pH?

No. Claim 1 requires a very specific copolyamino acid: glutamic/aspartic units with carboxylate charges and covalently attached hydrophobic radicals meeting the formula constraints and substitution/DP ranges.

3) How can a competitor avoid the patent without changing the polymer chemistry?

By changing the formulation boundary conditions that the claim fixes: pH outside 6.0 to 8.0, or polymer/glucagon concentrations and the [hydrophobic radical]/[glucagon] < 15 relationship (where applicable).

4) Do the optional additives (zinc, polyanions, gastrointestinal hormones) need to be present?

They map to dependent claims. If a competitor’s product includes those features, they may fall into those dependent claim scopes; if not, they may avoid those dependent features while still potentially facing Claim 1.

5) Does the patent threaten glucagon-only formulations or combination products as well?

Both. It covers glucagon formulations through Claim 1, and it also covers embodiments that include a “gastrointestinal hormone” from the defined GLP-1 mimetic set within specified concentration ranges.

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References

[1] United States Patent 10,485,851 (claims as provided in prompt).

Details for Patent 10,485,851

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Glaxosmithkline Llc	TANZEUM	albiglutide	For Injection	125431	April 15, 2014	10,485,851	2037-06-07
Eli Lilly And Company	TRULICITY	dulaglutide	Injection	125469	September 18, 2014	10,485,851	2037-06-07
Eli Lilly And Company	TRULICITY	dulaglutide	Injection	125469	September 4, 2020	10,485,851	2037-06-07
Sanofi-aventis U.s. Llc	ADLYXIN	lixisenatide	Injection	208471	July 27, 2016	10,485,851	2037-06-07