Details for Patent: 8,715,710

Summary for Patent: 8,715,710

Title:	Semi-solid delivery vehicle and pharmaceutical compositions for delivery of granisetron
Abstract:	A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.
Inventor(s):	Steven Y. Ng, Hui Rong Shen, Jorge Heller
Assignee:	Heron Therapeutics LLC
Application Number:	US13/552,083
Patent Claim Types: see list of patent claims	Composition; Compound;

Scope and claims analysis of US Patent 8,715,710 (granisetron polyorthoester semi-solid sustained-release; PEG monomethyl ether): what the claims cover and how to map design-arounds

US 8,715,710 claims a semi-solid, sustained and controlled-release formulation that uses (i) a specific polyorthoester polymer architecture (including defined repeating subunits and mole-fraction windows for acid-containing subunits), (ii) a defined class and dose range of polyethylene glycol monomethyl ether (PEG monomethyl ether) with an explicit molecular-weight range, and (iii) granisetron at low weight-percent (free base or acid addition salt), with further dependent claim limits on polymer molecular weight, granisetron dose, salt form, stability under irradiation/sterilization, particle size, and dispensation/needle gauge. The independent claim 1 drives the core coverage, while claims 2 and 3 narrow polymer structure and PEG MW, respectively.

The claim set is formulation-centric. It is not a method-of-treatment patent on granisetron’s indication. The landscape risk for generic or “follow-on” products is dominated by whether an accused formulation uses the same polymer class and compositional windows and whether it is designed to avoid the PEG monomethyl ether molecular-weight range and the polyorthoester subunit/mole-percent recitations.

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What is US 8,715,710’s core invention and what do independent claims 1 and 2 require?

Short answer: The patent protects a semi-solid granisetron formulation where granisetron is dispersed in a polyorthoester matrix plasticized or structured with PEG monomethyl ether (10 to 50 wt%), with granisetron at about 1 to 5 wt%, and with polyorthoester having (a) an overall polymer MW of 1,000 to 10,000 and (b) defined subunit composition including α-hydroxyacid-containing subunits at 0.1 to 25 mole%. Claim 2 adds an alternating-residue polymer construction using specific tetraoxaspiro undecane residues and a glycolide/triethylene-glycol derived “diol-ate” residue.

Claim 1: minimum elements for infringement (text-structure checklist)

Claim 1 defines:

1. Dosage form and physical state

   • “A semi-solid pharmaceutical composition.”

2. Polymer carrier: polyorthoester

   • Polyorthoester comprising subunits selected from the recited structural formula with variables:
     • “x is an integer from 1–4”
     • “the total amount of p is an integer from 1–20”
     • “s is an integer from 1–4”
   • α-hydroxyacid containing subunits mole percentage window
     • “from about 0.1 to about 25 mole percent”
   • Polyorthoester molecular weight window
     • “from 1000 to 10,000” (unit implied by patent drafting; no additional unit qualifier in the claim text provided)

3. Solubilizer/plasticizer: PEG monomethyl ether

   • Weight fraction
     • “10–50 weight percent”
   • Molecular weight window
     • “having a molecular weight in a range of 200 to 4,000”

4. Active

   • Granisetron at “about 1–5 weight percent.”

Practical construction points (for claim mapping)

• The claim is not limited to a single PEG MW. It is a class defined by MW range (200–4,000).
• The claim is not limited to a single polymer repeat ratio. It is framed by allowable integer parameters (x, p, s) and by mole% of α-hydroxyacid subunits.
• The composition requirement is simultaneous: the formulation must include the recited polyorthoester subunit distribution and the specified PEG monomethyl ether weight and MW ranges while containing granisetron in the claimed wt%.

Claim 2: stricter polymer architecture and defined “diol-ate” synthesis-derived residue

Claim 2 depends on claims 1/2 structure but narrows polyorthoester composition:

1. Alternating residues

   • Alternating residues of:
     • a defined “3,9-diethyl-3,9-2,4,8,10-tetraoxaspiro[5.5] undecane-3,9-diyl” residue, and
     • a “diol-ate residue” of triethylene glycol or of triethylene glycol diglycolide

2. Definition of triethylene glycol diglycolide by reaction condition

   • “prepared by reacting triethylene glycol with from 0.5 to 10 molar equivalents of glycolide at 100–200° C. for about 12 hours to 48 hours”
   • This ties the polymer residue definition to a preparation route/starting-material chemistry, which can matter in infringement analysis if the accused polymer is not produced by the same chemistry or cannot be shown to have the same residue.

3. Glycolide-containing subunits mole fraction window

   • “from about 0.1 to about 25 mole percent” (mole percentage of glycolide-containing subunits in the polyorthoester)

4. Polyorthoester MW

   • “molecular weight of 1000 to 10,000.”

5. PEG monomethyl ether and granisetron ranges

   • Still required:
     • PEG monomethyl ether 10–50 wt% (200–4,000 MW)
     • granisetron 1–5 wt%

Functional relevance

• Claim 2 focuses on a specific polymer building-block pairing and defines the glycolide/triethylene glycol-derived component via reaction parameters.
• If an accused product uses a different diol-ate origin or does not incorporate alternating tetraoxaspiro residues, it can avoid Claim 2 even if it might still fall within Claim 1.

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What specific compositional limits create the strongest infringement and the best design-around options?

Short answer: The most enforceable “hard stops” are the PEG monomethyl ether MW range (200–4,000), the PEG wt% (10–50), granisetron wt% (about 1–5), polyorthoester MW (1,000–10,000), and the α-hydroxyacid/glycolide subunit mole percent (0.1–25 mole%). Dependent claims add salt form, PEG MW ~550, granisetron dose ~2 wt%, stability properties, and performance constraints (particle size <100 microns; 16–25 gauge needle dispense; sustained and controlled release).

Claim 3: PEG monomethyl ether molecular weight “about 550”

Claim 3 narrows Claim 1/2 by requiring:

• PEG monomethyl ether MW: “about 550.”

Implication

• A product using PEG monomethyl ether with MW far from ~550 (yet still within 200–4,000) may evade Claim 3 while remaining within the broader Claim 1 window if other requirements are met.

Claim 4: granisetron content “from 2–3 weight percent”

Claim 4 narrows the granisetron wt% window of Claim 1/2:

• “from 2–3 weight percent granisetron.”

Implication

• Products at ~1.2–1.9 wt% or ~3.1–5.0 wt% may evade Claim 4 but still potentially infringe independent claim ranges.

Claim 5 and 6: granisetron form free base vs acid addition salt

Claim 5:

• granisetron in “free base” form.

Claim 6:

• granisetron in “acid addition salt” form.

Implication

• Both forms are explicitly covered, reducing the design-around value of changing salt form unless an accused formulation uses a form not treated as “granisetron” by the claim scope (rare for typical granisetron salts) or shifts beyond the claimed composition windows.

Claim 7: exemplary “center of gravity” formulation

Claim 7 specifies:

• 78.4 wt% polyorthoester
• 19.6 wt% PEG monomethyl ether
• 2 wt% granisetron

Implication

• This is both a literal target and a claim-support anchor for interpreting broader ranges.

Claim 8: polyorthoester MW “about 6,500”

Claim 8 narrows to:

• polyorthoester MW: “about 6,500.”

Implication

• A product with polyorthoester MW within 1,000–10,000 but not near ~6,500 may fall within Claim 1 yet avoid Claim 8.

Claim 9: stability upon irradiation

Claim 9:

• composition “stable upon irradiation.”

Implication

• This is a dependent claim tied to a property. In litigation, it can become a proof point and an argument hook for claim validity/infringement (depending on how the specification defines “stable” and what test/threshold is used). A design-around may target photolabile components or include stabilizers that still maintain stability but could dispute whether the test meets the claim’s “stable” requirement.

Claim 10: stability upon sterilization

Claim 10:

• composition “stable upon sterilization.”

Implication

• Another property limitation. It can matter for manufacturing processes and for comparing specific sterilization conditions.

Claim 11: granisetron particle size <100 microns

Claim 11:

• granisetron “solid having a particle size of less than 100 microns.”

Implication

• If an accused product uses granisetron dispersed as smaller/nanoparticle equivalents, it still falls under <100 microns. A design-around would need to increase particle size above the threshold or change the dispersion state in a way that challenges whether it meets the “solid” criterion as drafted.

Claim 12: dispensation from 16–25 gauge needle

Claim 12:

• composition “capable of being dispensed from a 16–25 gauge needle.”

Implication

• This is an operational rheology/performance limitation that can be measured. It is often used to distinguish semi-solids with different viscosity profiles.

Claim 13: effective to release granisetron in a sustained and controlled manner

Claim 13:

• “effective to release the granisetron in a sustained and controlled manner after administration.”

Implication

• This ties the formulation to release kinetics. A design-around may target burst release or different release profile. If an accused formulation still shows sustained release, the limitation is met.

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What patents and claims typically surround this estate in the US: polymer, excipient, and granisetron formulation clusters?

Short answer: US 8,715,710 is best treated as part of a formulation-and-polymer-architecture cluster: polyorthoester chemistry patents (subunit selection, molecular weight control, degradation/release tuning) plus formulation patents pairing those polymers with granisetron and PEG monomethyl ether. Without the full bibliographic data for the patent’s assignee, priority chain, and cited references, a complete landscape map across all related family members cannot be produced from the claim text alone.

Per your constraint set, this response is limited to what is supported by the claim text you provided: US 8,715,710’s scope boundaries and infringement-relevant elements. A broader “which patents in the family” and “what other US patents cite/are cited by it” analysis requires bibliographic and citation data not included here.

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How do the claim limitations translate into infringement risk for an “accused” semi-solid granisetron depot?

Short answer: The biggest infringement determinations will be (1) whether the carrier is a polyorthoester with the defined subunit composition and MW window, (2) whether the formulation uses PEG monomethyl ether at 10–50 wt% with PEG MW 200–4,000, and (3) whether granisetron is present at about 1–5 wt%. Secondary dependent limits (salt form, particle size, needle dispense, irradiation/sterilization stability) decide additional claim coverage even when the core independent claim is already met.

Scenario mapping: likely worst-case infringement profile

An accused product is high risk if it has:

• Semi-solid granisetron composition
• Polyorthoester MW between 1,000 and 10,000 and containing α-hydroxyacid (Claim 1) at 0.1–25 mole%
• PEG monomethyl ether present at 10–50 wt%, PEG MW within 200–4,000
• Granisetron present at about 1–5 wt%

If it also uses:

• PEG monomethyl ether MW ~550 (Claim 3)
• Granisetron ~2 wt% or 2–3 wt% (Claims 4 and/or 7)
• Polyorthoester MW ~6,500 (Claim 8)
• Granisetron free base or acid addition salt (Claims 5 or 6)
• Particle size <100 microns (Claim 11)
• Needle dispense 16–25 gauge (Claim 12)
• Demonstrated sustained controlled release (Claim 13) then additional dependent claim coverage increases materially.

Design-around levers (directly tied to claim text)

Most direct “claim-evasive” actions are to miss at least one hard numeric or definitional element:

1. PEG monomethyl ether exclusion

   • Use a different PEG species (e.g., PEG different end group or different MW outside 200–4,000) or reduce PEG monomethyl ether wt% below 10 or above 50.

2. Granisetron loading outside about 1–5 wt%

   • Move granisetron dosing outside the claimed wt% range (exact “about” tolerance would depend on the specification, but the numeric anchors are clear).

3. Polyorthoester MW outside 1,000–10,000

   • Reformulate polymer MW outside the window.

4. Subunit mole fraction outside 0.1–25 mole%

   • Tune α-hydroxyacid subunits (Claim 1) or glycolide subunits (Claim 2) outside the 0.1–25 mole% range.

5. Polymer architecture change

   • Avoid alternating residues of the defined tetraoxaspiro undecane residue plus triethylene glycol or triethylene glycol diglycolide residue as specified in Claim 2.

6. Avoidance of dependent performance/property recitations

   • While these are harder to “design-out” without changing the product’s functional profile, they can be used tactically:
     • maintain particle size ≥100 microns
     • adjust rheology so dispensing is not possible from 16–25 gauge needles
     • alter release to not be “sustained and controlled”
     • show lack of stability under irradiation or sterilization test conditions used by the claim/supported disclosure

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How would claim scope differ between Claim 1 versus Claim 2 in licensing negotiations?

Short answer: Claim 1 is broader on polyorthoester subunit type (α-hydroxyacid-containing subunits within a mole fraction and variable repeating-unit parameters) but narrower in requiring PEG monomethyl ether MW and wt% ranges plus granisetron wt% ranges. Claim 2 narrows the polymer architecture and adds residue-source definition tied to glycolide reaction parameters.

In licensing terms:

• A potential licensee whose polymer is “close” structurally but uses different diol-ate chemistry or different alternating residues is more likely to clear Claim 2 but still face Claim 1.
• A licensee whose formulation meets Claim 1 but not Claim 2 could negotiate narrower rights focused on the polyorthoester class and the PEG/granisetron compositional windows.

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Key takeaways

• US 8,715,710 protects a semi-solid granisetron formulation built on a polyorthoester carrier with defined subunit composition (α-hydroxyacid-containing subunits at 0.1–25 mole%) and polyorthoester molecular weight (1,000–10,000).
• The formulation must include PEG monomethyl ether at 10–50 wt% with PEG MW 200–4,000, plus granisetron at about 1–5 wt%.
• Claim 2 adds a specific alternating polymer residue architecture with a tetraoxaspiro undecane residue and a triethylene glycol or triethylene glycol diglycolide (made from glycolide with defined molar equivalents and thermal/time conditions) diol-ate residue, with glycolide subunit mole% also at 0.1–25.
• Dependent claims tighten coverage via:
  • PEG MW ~550,
  • granisetron 2–3 wt% or 2 wt%,
  • polyorthoester MW ~6,500,
  • stability upon irradiation and sterilization,
  • granisetron particle size <100 microns,
  • dispense through 16–25 gauge needle,
  • sustained and controlled release after administration.
• The highest-value design-around is to break one of the core numeric windows or the polymer architecture (PEG MW/wt%, granisetron wt%, polyorthoester MW, α-hydroxyacid/glycolide mole% or the alternating-residue scheme).

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FAQs

1) Can a product that uses granisetron at 5 wt% avoid infringement?
If it is within the “about 1–5 weight percent” range, it remains inside the independent claim’s granisetron window; shifting slightly above the top end of “about” is the straightforward risk-reduction path, but the claim text anchors the range at 5.

2) Does changing granisetron from free base to a different granisetron salt avoid the patent?
Claims 5 and 6 explicitly cover both free base and acid addition salt, so the salt/free-base switch does not avoid coverage by itself if it is still “granisetron” in the claimed forms and meets the wt% and carrier limitations.

3) What is the most discriminating parameter between Claim 1 and Claim 2?
Polymer architecture: Claim 2 requires alternating tetraoxaspiro undecane residues with a diol-ate residue derived from triethylene glycol or triethylene glycol diglycolide prepared under specified glycolide reaction conditions.

4) If we use PEG monomethyl ether with MW outside 200–4,000, do we still face Claim 1?
No, if PEG monomethyl ether MW is outside the claimed 200–4,000 range (and PEG monomethyl ether itself is not within that definition), Claim 1’s excipient limitation is missed.

5) Are needle gauge and particle size requirements independent from the sustained-release requirement?
Yes. Claim 12 (16–25 gauge dispensing) and Claim 11 (granisetron particle size <100 microns) are separate dependent limitations from Claim 13’s sustained and controlled release effectiveness; a formulation can meet one without meeting the others.

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References

No source references are provided because only the claim text was provided and no bibliographic or citation data were included for US 8,715,710.

Drugs Protected by US Patent 8,715,710

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 8,715,710

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005289425
Canada	2579297
China	101052376
European Patent Office	1796629
European Patent Office	2902012