Patent: 6,245,740

Summary for Patent: 6,245,740

Title:	Polyol:oil suspensions for the sustained release of proteins
Abstract:	The present invention relates to the preparation of polyol/thickened oil suspensions containing a biologically active agent, for the sustained delivery of the biologically active agent. The described protein/glycerol/oil suspensions show sustained release of protein, e.g., G-CSF, of up to at least one week.
Inventor(s):	Goldenberg; Merrill (Thousand Oaks, CA), Shan; Daxian (Thousand Oaks, CA), Beekman; Alice (Thousand Oaks, CA)
Assignee:	Amgen Inc. (Thousand Oaks, CA)
Application Number:	09/221,181
Patent Claims:	see list of patent claims

US Patent 6,245,740: G-CSF Sustained-Release Polyol:Oil Suspension Claims and US Patent Landscape

US Patent 6,245,740 claims sustained-release formulations of granulocyte-colony stimulating factor (G-CSF) using a two-step suspension build: G-CSF in a biocompatible polyol, then suspension of that mixture in thickened oil (a polyol:oil system) with polyol at 15% to 30% by weight. The claims also define a composition-anchoring selection set for polyols, thickeners, oils, and a corresponding preparation process plus a parenteral dosing method with release “up to one week or more.”

What does the patent actually claim? (Independent claim 1 and dependent scope)

Claim 1 (core formulation and process structure)

Claim 1 is written as a sustained-release composition plus a process characterization that ties identity to preparation steps. The material limitation chain is:

1) Active + carrier architecture

• G-CSF is incorporated into a biocompatible polyol:oil suspension
• Thickener is present in the suspension

2) Two-stage suspension preparation

• (a) Suspend G-CSF powder in a polyol to form G-CSF:polyol mixture
• (b) Suspend the G-CSF:polyol mixture in a mixture comprising a thickened oil to form G-CSF:polyol:oil suspension

3) Polyol content window

• Polyol level is 15% to 30% by weight of the suspension

4) Functional outcome

• The composition is “sustained-release” with release from the suspension (claim 8 specifies up to one week or more)

Claim 1 is therefore not a broad “any sustained release G-CSF oil suspension.” It is structurally and process anchored: polyol concentration window + thickened oil + two-stage suspension starting from powder.

Claim 2 (polyol selection set)

Claim 2 limits the “biocompatible polyol” to:

• glycerol, erythritol, arabinose, xylose, ribose, inositol, fructose, galactose, maltose, sucrose

This is a closed list, but still covers common polyols and sugars used for stabilizing protein formulations and for viscosity/phase behavior.

Claims 3-5 (thickener selection and hardening)

Claim 3 limits thickener to:

• polyvalent metal salts of organic acids, waxes, and high viscosity oils

Claim 4 narrows to:

• aluminum monostearate

Claim 5 narrows further to:

• white wax

These are meaningful for enforceability. Aluminum monostearate and waxes represent concrete, checkable materials, which can be used to distinguish prior art and also to design-around only if alternatives are used that fall outside the claim language.

Claim 6 (oil selection set)

Claim 6 limits oil to:

• sesame, castor, cottonseed, canola, saffron, olive, peanut, sunflower seed
• and α-tocopherol
• and ethyl oleate

The presence of α-tocopherol and ethyl oleate expands the “oil” bucket beyond triglyceride seed oils and supports formulations where oleate esters or vitamin E derivatives contribute to phase behavior and viscosity.

Claim 7 (process claim mirroring claim 1)

Claim 7 repeats the two-stage process with the same 15% to 30% polyol by weight limit. It is the same inventive skeleton, but framed as a preparation method.

Claim 8 (administration and release duration)

Claim 8 recites:

• parenteral administration to warm-blooded animal
• subcutaneous or intramuscular
• controlled release for up to one week or more

Claim 8 adds clinical context and delivery route, but it does not define pharmacokinetic parameters, dose amounts, or release kinetics beyond duration.

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What is the claim “center of gravity” for infringement?

For US infringement analysis, claim 1 and claim 7 dominate because they define the formulation identity through:

• polyol:oil suspension
• thickener presence
• polyol at 15% to 30% by weight
• two-stage suspension build from G-CSF powder in polyol, then into thickened oil
• a sustained-release functional statement (which is typically supported by specification and product performance)

Design-around is most likely to occur via any of these anchors:

• move polyol outside 15% to 30%
• remove the thickener or use one that is outside claim 3 categories (depending on interpretation)
• avoid the literal “suspending powder in polyol” construction (process language can be hard to avoid because commercial manufacturing can still be characterized as suspending, even if milling or emulsification is used)
• remove oils outside claim 6 if using a different oil phase

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How defensible are the claims against typical G-CSF sustained-release prior art?

Key vulnerability: “sustained-release injectable G-CSF” is a crowded space

The historical landscape for G-CSF sustained release includes:

• albumin-based or depot formulations
• polymer micro/nanoparticles (PLA/PLGA, etc.)
• liposomes/emulsions
• oil-based depots with thickeners or viscosity agents
• encapsulation technologies

Because G-CSF itself is known, novelty usually relies on composition construction and process-defined composition features. Claim 1 does that via polyol:oil system, thickened oil, and polyol percentage window. Those features can confer novelty even in crowded depots, but they can also be narrow enough to allow easy prior-art knockouts if any earlier patent disclosed the same architecture and concentration window.

Key vulnerability: polyol:oil systems for protein stabilization

Polyols like glycerol and sugars have been used broadly as stabilizers, cryo/lyoprotectants, and viscosity modifiers. If prior art disclosed:

• G-CSF suspended in glycerol or similar polyols, and then
• mixed into oil systems with thickening, the main remaining differentiator becomes the 15% to 30% polyol by weight and the specific thickener/oil categories.

Key vulnerability: thickened oil with aluminum monostearate or waxes

Aluminum monostearate and wax thickeners are common in suspension and depot formulations for viscosity and phase control. If earlier G-CSF depot patents used:

• aluminum monostearate or waxes with an oil continuous phase, then claims 3-5 could be at risk unless the polyol window and specific process were not present.

Claim drafting strength

Claim 1’s drafting structure has strength:

• It is not merely “G-CSF sustained release in polyol and oil.”
• It requires polyol in a specified concentration range and requires thickener presence.
• It includes process steps, which can limit combinations that could otherwise be characterized as obvious variants.

The practical enforceability depends heavily on whether the specification supports the process characterization and whether the polyol window is a true technical driver of sustained release.

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What is the patent landscape likely to look like in the US? (Critical map of adjacent claim territories)

Because the user supplied only claim text and not the patent’s bibliographic data (assignee, filing date, publication date, priority claims), a complete, dated family-by-family US landscape cannot be reliably reconstructed. Under operating constraints, only structurally grounded, claim-territory mapping can be provided.

Below is a landscape map by technical “claim territory,” which is how freedom-to-operate and validity analyses are usually executed.

Territory A: G-CSF in oil depots with thickening agents

Claim overlap risk: Medium to high

• Many depot patents use oils plus thickeners for viscosity, injectability, and depot stability.
• Aluminum monostearate and waxes are standard thickening agents.

Distinguishing features in 6,245,740:

• polyol:oil is specifically a suspension built in two stages
• polyol at 15% to 30% by weight
• polyol is from a closed list in dependent claim 2
• oils are from a closed list in claim 6

Territory B: Protein/polyol formulations for stabilization, then depot dosing

Claim overlap risk: Medium

• Polyols and sugars are commonly used for protein stabilization.
• If prior art disclosed G-CSF suspended in glycerol at relevant levels, then moved into oil depots, the main remaining distinction is the specific concentration window and thickened oil build.

Territory C: Polymer-based sustained-release G-CSF (PLA/PLGA, microspheres, implants)

Claim overlap risk: Lower for literal infringement

• These systems are not “polyol:oil suspensions” and do not require the same polyol concentration window or thickened oil suspension.
• They remain important for validity only if prior art broad claims encompass “depot sustained release” generally, but literal claim language should keep them out.

Territory D: Liposomal or emulsion depots

Claim overlap risk: Low to medium

• Liposomes/emulsions can be oils with dispersed aqueous phase, but claim 1 requires a specific sustained-release polyol:oil suspension with thickener and a build from G-CSF powder suspended in polyol, then into thickened oil.
• If earlier systems used a two-phase emulsion but not the same suspension architecture or polyol window, literal overlap decreases.

Territory E: “G-CSF depot with specific oils and thickeners”

Claim overlap risk: Medium to high

• Oils listed in claim 6 are conventional.
• If prior art used those oils with thickeners and polyols in relevant windows, then claim 6 becomes vulnerable.

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Claim-by-claim competitive implications (how others would design around)

Polyol window (15% to 30% by weight) is the most direct switch

A competitor can target:

• <15% polyol or >30% polyol to avoid both claim 1 and claim 7 on that explicit numeric limitation.

This is a clean design-around if sustained release can still be achieved.

Thickener category is the second switch

Claim 3 is moderately broad but still category-bound:

• polyvalent metal salts of organic acids
• waxes
• high viscosity oils

Avoiding these categories can be hard if the competitor’s viscosity agent falls into “waxes” or “high viscosity oils” by claim construction. Aluminum monostearate and white wax are directly targeted by dependent claims 4-5.

Oil choice is the third switch

Claim 6 is a closed list. If a competitor uses:

• a different triglyceride (not in list),
• a synthetic ester not in list,
• or a mixed oil phase, then claim 6 might not read, depending on how claim 1 is interpreted (claim 1 does not explicitly restrict oil identity; claim 6 does).

Process-anchoring risk

Claim 1 and claim 7 require:

• suspending G-CSF powder in polyol, then suspending the resulting mixture in thickened oil.

If a competitor uses:

• pre-made gels,
• lyophilized particulates reconstituted in situ,
• or emulsification steps instead of suspension of powder, a literal reading could still capture “suspending” depending on how broadly courts interpret the term and whether the product ends up the same.

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What claims are most likely to be attacked for obviousness or lack of novelty?

Most likely novelty attack targets

• Claim 1’s suspension architecture (polyol:oil + thickener)
• numeric polyol window (15% to 30%) as a range that might be disclosed or suggested
• claim 3-6 selection lists as obvious substitutions of standard excipients in known depots

Most likely non-infringement handles

• polyol content outside 15% to 30%
• no thickener, or thickener not falling into claim 3 categories
• different oil outside claim 6
• different process character (if a competitor’s manufacturing is not reasonably characterized as powder suspended in polyol then into thickened oil)

Most likely commercial risk areas

If a product uses:

• glycerol or erythritol at 15% to 30% by weight,
• aluminum monostearate or white wax,
• in a listed oil, then it would land near the claim’s literal perimeter.

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Key takeaways (business and R&D implications)

• US 6,245,740 is centered on a specific formulation perimeter: G-CSF suspended in a polyol:oil system with thickener, built in two suspension steps, with polyol at 15% to 30% by weight.
• Numeric limitation is the clearest design-around lever. Moving polyol outside 15% to 30% can avoid claims 1 and 7.
• Dependent claims narrow excipient choices into closed lists (polyols in claim 2; oils in claim 6; aluminum monostearate/white wax in claims 4-5), increasing the specificity of both infringement risk and validity arguments.
• Prior art in depot formulation for proteins is extensive, so defensibility likely depends on whether earlier patents disclose the same polyol:oil suspension architecture plus the specific polyol weight window.
• Process language may constrain “look-alike” formulations if competitors cannot characterize their manufacturing as “suspending G-CSF powder in polyol” then “suspending in thickened oil.”

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FAQs

1) Does claim 1 require a particular oil by identity?

Claim 1 requires a “biocompatible polyol:oil suspension” with thickener, but it does not restrict the oil identity in claim 1 itself. Claim 6 restricts oil identity for that dependent scope.

2) Is the sustained-release aspect an independent limitation or just a statement of intended effect?

It appears as a functional characterization in claim 1 and is operationalized in claim 8 with release duration (“up to one week or more”), but the enforceability of functional language depends on claim interpretation and specification support.

3) Which single parameter is most effective for design-around?

The polyol content (15% to 30% by weight) is the most direct, objective limitation.

4) How do aluminum monostearate and white wax affect infringement risk?

They are explicitly captured in dependent claims 4 and 5. Formulations using those thickeners at least within the claim architecture would fall closer to those dependent scopes.

5) Can a competitor avoid infringement by using a different thickener class?

Potentially. Claim 3 limits thickener to specific categories (metal salts of organic acids, waxes, high viscosity oils). Using thickeners outside those categories can be a practical non-infringement strategy.

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References

[1] United States Patent 6,245,740. (claims as provided in prompt).

Details for Patent 6,245,740

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Pharmacia & Upjohn Company Llc	SOMAVERT	pegvisomant	For Injection	021106	March 25, 2003		2018-12-23
Pharmacia & Upjohn Company Llc	SOMAVERT	pegvisomant	For Injection	021106	July 31, 2014		2018-12-23
Aimmune Therapeutics, Inc.	PALFORZIA	peanut (arachis hypogaea) allergen powder-dnfp	Powder	125696	January 31, 2020		2018-12-23