United States Patent 9,913,910: Granisetron Polyorthoester Patent Scope, Exclusivity and Competitive Landscape

U.S. Patent No. 9,913,910 protects a narrow but commercially important combination: prophylactic administration of granisetron at 1% to 5% by weight in a semi-solid injectable delivery vehicle containing a specified polyorthoester and polyethylene glycol monomethyl ether. The patent is directed to the formulation and its clinical use, not to granisetron as a molecule.

The principal commercial relevance is Sustol, an extended-release subcutaneous granisetron product developed by Heron Therapeutics, Inc. The claims create meaningful barriers against an ANDA product that copies the same polymer, PEG component, concentration range and subcutaneous antiemetic use. The estate is more vulnerable to a formulation design-around than to a conventional generic copy of granisetron injection.

What does U.S. Patent 9,913,910 protect?

The patent's independent claim 1 requires all of the following:

Limitation	Required scope
Therapeutic purpose	Prophylactic treatment of nausea and vomiting
Active ingredient	Granisetron
Granisetron concentration	1% to 5% by weight
Dosage form	Pharmaceutical composition with a semi-solid delivery vehicle
Polymer	Polyorthoester within the claimed formula I
Polymer substituents	R* is ethyl; A units include specified R1 and R3 structures
R1 content	About 0.05 to 30 mol% of A units
Solubilizing or modifying excipient	Polyethylene glycol monomethyl ether
Administration	Not expressly limited in claim 1, but dependent claims focus on injection and subcutaneous injection

The claim is a combined composition-and-method claim. A defendant would generally need to show that the accused product or use lacks at least one required limitation. Merely substituting a different granisetron salt or changing a nonessential excipient may not avoid infringement if the resulting product still falls within the claim language or is captured under the doctrine of equivalents.

The patent does not broadly cover:

All granisetron formulations;
All extended-release antiemetic formulations;
All polyorthoester drug-delivery systems;
Granisetron tablets, oral solutions or transdermal systems;
A conventional immediate-release granisetron injection;
Every use of granisetron for chemotherapy-induced nausea and vomiting.

Its value lies in the specific delivery platform and the associated prophylactic use.

How do the dependent claims narrow the patent scope?

Claims 2 through 18 add clinical, administration and formulation limitations.

Clinical-use limitations

Claims 2 and 3 cover:

Chemotherapy-associated nausea and vomiting;
Acute nausea and vomiting;
Delayed nausea and vomiting.

Claims 4 and 5 cover use with another antiemetic. These claims are relevant to multi-drug antiemetic regimens, including combinations involving corticosteroids or neurokinin-1 antagonists.

Administration limitations

Claims 6 and 7 require injection or subcutaneous injection. Claim 8 narrows the delivery device to a syringe using a 16- to 25-gauge needle.

These claims align closely with the commercial subcutaneous administration of Sustol. They are potentially important in a product-specific infringement case because the route of administration, syringe configuration and needle gauge may be identifiable from the FDA label, product instructions and marketing materials.

PEG limitations

Claims 9 through 12 require polyethylene glycol monomethyl ether with:

Molecular weight of 200 to 4,000;
Total concentration of 5% to 60% by weight under claim 10;
PEG monomethyl ether 550 under claims 11 and 12.

Claim 17 separately expands the PEG concentration to 5% to 80% by weight. Because claim 17 depends directly from claim 1 rather than claim 9, it does not require the molecular-weight range in claim 9.

Specific formulation limitation

Claim 13 covers a composition containing:

78.4% polyorthoester;
19.6% polyethylene glycol monomethyl ether;
2% granisetron.

This is the most product-specific claim in the set. It can provide a strong infringement theory where the commercial formulation matches those concentrations, subject to the meaning of the percentages, manufacturing tolerances and the precise polymer composition.

Claims 14 through 16 narrow the polymer structure by specifying:

p of 1 to 7 in a portion of the formula I units;
x equal to 2 in a portion of the units;
s equal to 2 in a portion of the units.

Claim 18 narrows the R1 content to about 0.1% to 25 mol% of the A units.

What is the patent expiration date for U.S. Patent 9,913,910?

U.S. Patent 9,913,910 was granted on February 13, 2018. Its effective patent term is determined by the earliest effective nonprovisional priority filing, subject to patent-term adjustment, patent-term extension and any terminal disclaimer.

The patent family is generally associated with a projected base term extending into approximately November 2029. The operative expiration date for freedom-to-operate and ANDA strategy must be determined from the USPTO patent-term calculation and any FDA patent-term extension record. The grant date itself is not the expiration date.

The patent should be analyzed with related continuation and continuation-in-part patents because a later-issued patent may extend protection for narrower formulations, manufacturing methods or alternative use claims even if the 9,913,910 claims expire.

What is the FDA and Orange Book status of the patent?

Sustol, the commercial product associated with this patent estate, received FDA approval under NDA 209241. It contains extended-release granisetron and is administered subcutaneously for the prevention of acute and delayed nausea and vomiting associated with moderately emetogenic chemotherapy or anthracycline and cyclophosphamide combination chemotherapy.

The Orange Book is the relevant FDA source for patents submitted in connection with the approved NDA. A method-of-use patent can be listed if it claims an approved use of the drug. A formulation patent may also be listed when it claims the approved drug product or an approved formulation.

For an ANDA applicant, the key regulatory consequences are:

ANDA certification	Practical effect
Paragraph I	No patent information is listed
Paragraph II	Listed patent has expired
Paragraph III	Applicant will not market until patent expiration
Paragraph IV	Applicant asserts that the patent is invalid, unenforceable or not infringed
Section viii statement	Applicant carves out a patented method of use, where permitted

Because the 9,913,910 claims cover a method of prophylactic use and the approved product is a specialized extended-release injection, a Paragraph IV strategy would likely need to address both formulation infringement and the scope of the approved use.

Which companies are challenging the patent?

No publicly reported Paragraph IV litigation involving U.S. Patent 9,913,910 was identified in the supplied record. No publicly documented settlement agreement involving this patent is established by the information provided.

The absence of a reported challenge does not eliminate future ANDA risk. A generic applicant could pursue:

A Paragraph III certification with delayed launch;
A Paragraph IV certification challenging validity or infringement;
A section viii carve-out directed to chemotherapy-associated use;
A non-infringing formulation using a different polymer or delivery vehicle.

For an ANDA applicant, a direct copy would carry greater risk because the claim set reaches the combination of polymer, PEG monomethyl ether, granisetron concentration and prophylactic use.

How strong is the patent estate for Sustol?

The 9,913,910 patent is strongest against a product that replicates the commercial formulation and subcutaneous use. Its strength is lower against products that change the delivery platform.

Strengths

Claim 1 combines formulation and clinical-use limitations.
Claim 13 targets a highly specific 78.4/19.6/2 formulation.
Claims 6 through 8 provide route and device-specific coverage.
Claims 9 through 12 identify PEG molecular-weight and PEG 550 embodiments.
The claim set covers both acute and delayed chemotherapy-induced nausea and vomiting.
The composition is technically differentiated from conventional granisetron injection.

Weaknesses and attack points

The independent claim contains numerous structural limitations.
The polymer formula may create claim-construction and enablement disputes.
Terms such as "about," "a portion of the units," and "semi-solid" may require expert testimony.
A competing product may avoid infringement with a different biodegradable polymer.
Granisetron concentration outside 1% to 5% may avoid claim 1, although commercial and clinical constraints limit the usefulness of that approach.
A product using PEG rather than PEG monomethyl ether, or a different co-solvent, may create a non-infringement position.
A conventional immediate-release injection would not normally satisfy the semi-solid polyorthoester limitation.

The patent is therefore commercially meaningful but formulation-sensitive. It is not a broad molecule patent.

What formulations are protected by the patent?

The most important protected formulation characteristics are:

Polyorthoester with ethyl R* substitution;
A specified fraction of R1-containing A units;
Polyethylene glycol monomethyl ether;
Granisetron at 1% to 5% by weight;
Preferably PEG monomethyl ether 550;
A semi-solid composition suitable for injection;
In the narrowest commercial embodiment, 78.4% polyorthoester, 19.6% PEG monomethyl ether and 2% granisetron.

The claims do not require every formulation to contain PEG 550. PEG molecular weights from 200 to 4,000 are covered by claim 9, while claims 11 and 12 specifically identify PEG 550.

What generic launch scenarios exist?

Scenario 1: Direct copy

A generic applicant copies the polyorthoester, PEG monomethyl ether, granisetron concentration and subcutaneous chemotherapy indication. This is the highest-risk scenario for infringement and would likely invite a Paragraph IV dispute.

Scenario 2: Polymer substitution

The applicant uses another sustained-release polymer, such as a different polyester, depot polymer or in situ gelling system. This presents a stronger non-infringement position because the polyorthoester limitation is central to claim 1.

Scenario 3: Route substitution

The applicant develops an oral, transdermal or conventional intravenous product. Such a product may compete therapeutically but would generally avoid the subcutaneous injection claims and may not meet the semi-solid vehicle limitation.

Scenario 4: Concentration or excipient modification

A product outside the 1% to 5% granisetron range or without polyethylene glycol monomethyl ether could avoid literal infringement. The commercial feasibility of that strategy depends on dose uniformity, syringeability, release profile and clinical performance.

Scenario 5: Use carve-out

An ANDA applicant could attempt to omit the patented chemotherapy prophylaxis use from labeling. This strategy is difficult where the product's principal approved use, promotional materials or prescribing information still direct the product toward the claimed indication.

How does Sustol compare with competing antiemetic products?

Product or category	Active ingredient	Delivery	Main competitive distinction
Sustol	Granisetron	Extended-release subcutaneous injection	Long-acting 5-HT3 antagonist depot
Generic granisetron injection	Granisetron	Immediate-release injection	Lower-cost conventional alternative
Kytril and generic oral granisetron	Granisetron	Oral	No polyorthoester depot
Sancuso	Granisetron	Transdermal patch	Extended delivery without injection
Aloxi	Palonosetron	Intravenous or oral	Long-acting 5-HT3 antagonist
Ondansetron products	Ondansetron	Oral, injectable, transdermal	Broad generic competition
NK1/5-HT3 combinations	Varies	Oral or injectable	Combination antiemetic regimen

Sustol's patent position is most relevant against another long-acting injectable granisetron product, not against all antiemetic competitors.

What manufacturing and intellectual-property barriers exist?

The principal manufacturing barrier is the reproducible preparation of the polyorthoester vehicle with controlled:

Polymer molecular weight;
R1 molar percentage;
Substituent distribution;
Degradation rate;
Granisetron uniformity;
PEG content;
Syringeability and injection force;
In vivo release profile.

A competitor may avoid the literal claims but still face process-development and regulatory-equivalence challenges. For an ANDA applicant, demonstrating pharmaceutical equivalence to a semi-solid extended-release injectable product can be more difficult than duplicating an immediate-release solution.

The broader patent landscape may include related patents covering polyorthoester chemistry, depot delivery systems, manufacturing methods and additional granisetron formulations. Those patents should be reviewed as a family rather than treating 9,913,910 as the entire estate.

What is the revenue exposure associated with this patent?

Heron Therapeutics has commercial exposure to Sustol, but publicly reported company disclosures may aggregate product revenue rather than separately disclose revenue attributable to this patent. The patent's economic value depends on Sustol sales, pricing, payer coverage, chemotherapy-site adoption and the availability of lower-cost granisetron alternatives.

The highest-value period is the remaining protected life of the formulation and use claims. A successful Paragraph IV launch would affect the product's price, contracting position and treatment-center utilization. A design-around competitor could enter without invalidating the patent but would require a clinically and regulatorily acceptable alternative depot system.

Key Takeaways

U.S. Patent 9,913,910 is a formulation-and-method patent for granisetron in a polyorthoester and PEG monomethyl ether semi-solid delivery vehicle.
Claim 1 requires granisetron at 1% to 5% by weight and a specifically defined polyorthoester structure.
Claims 6 through 8 focus on injection, subcutaneous administration and syringe needle gauge.
Claim 13 protects the highly specific 78.4% polyorthoester, 19.6% PEG monomethyl ether and 2% granisetron composition.
The patent is materially relevant to Sustol and its extended-release subcutaneous granisetron platform.
The projected base term extends into approximately November 2029, subject to USPTO term adjustments and any applicable extension.
The principal generic risks are direct copying and Paragraph IV litigation.
The most credible design-around paths involve a different polymer, a different PEG derivative, a different route or a non-depot granisetron formulation.
Biosimilar risk is not applicable because granisetron is a small-molecule drug.
No publicly reported Paragraph IV challenge or settlement involving this patent is established in the supplied record.

FAQs About U.S. Patent 9,913,910

Does U.S. Patent 9,913,910 cover generic granisetron injection?

No. It does not broadly cover conventional immediate-release granisetron injection. The claims require a semi-solid vehicle containing the specified polyorthoester and polyethylene glycol monomethyl ether.

Does the patent cover intravenous administration?

Claim 1 is not expressly limited to a route, but dependent claims 6 through 8 focus on injection and subcutaneous injection. An intravenous product would still need to satisfy every limitation of claim 1 to create literal infringement.

Can a competitor avoid the patent by using PEG 400 instead of PEG 550?

Possibly. PEG molecular weights from 200 to 4,000 are covered by claim 9, so PEG 400 remains within that dependent-claim range. A complete analysis would also require review of the polymer and all other claim limitations.

Is a biosimilar application required for a competing Sustol product?

No. Granisetron is a small molecule. A competing product would ordinarily proceed through the abbreviated new drug application pathway or a full NDA pathway, depending on the product and regulatory strategy.

What is the most valuable claim for an infringement case?

Claim 1 is the principal enforcement claim because it combines the therapeutic use with the core composition. Claim 13 may be highly probative when the accused product matches the commercial 78.4/19.6/2 formulation.

References

U.S. Patent No. 9,913,910, Methods and compositions for treatment of nausea and vomiting (2018). United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2018). Sustol (granisetron) extended-release injection prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
United States Patent and Trademark Office. (n.d.). Patent Center and patent term information for U.S. Patent No. 9,913,910.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005289425	⤷ Start Trial
Canada	2579297	⤷ Start Trial
China	101052376	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,913,910

Summary for Patent: 9,913,910