Details for Patent: 8,911,786

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Which drugs does patent 8,911,786 protect, and when does it expire?

Patent 8,911,786 protects FYARRO and is included in one NDA.

This patent has sixty-nine patent family members in twenty-three countries.

Summary for Patent: 8,911,786

Title:	Nanoparticle comprising rapamycin and albumin as anticancer agent
Abstract:	The present invention features methods for treating, stabilizing, preventing, and/or delaying cancer by administering nanoparticles that comprise rapamycin or a derivative thereof. The invention also provides compositions (e.g., unit dosage forms) comprising nanoparticles that comprise a carrier protein and rapamycin or a derivative thereof. The invention further provides combination therapy methods of treating cancer comprising administering to an individual an effective amount of nanoparticles that comprise rapamycin or a derivative thereof and a second therapy.
Inventor(s):	Neil P. Desai, Patrick Soon-Shiong, Vuong Trieu
Assignee:	Abraxis Bioscience LLC
Application Number:	US12/530,188
Patent Claim Types: see list of patent claims	Use; Composition; Device; Dosage form;

US Patent 8,911,786: Claim Scope, Fyarro Exclusivity, and Albumin-Bound Rapamycin Patent Landscape

US Patent 8,911,786 protects specific cancer uses of albumin-coated rapamycin nanoparticles, including the product now marketed as Fyarro, or nab-sirolimus. The core limitations are a rapamycin-based nanoparticle coated with albumin, an average particle diameter of no more than about 200 nm, and a rapamycin dose of about 54 mg to 180 mg. The patent also covers unit-dose products, kits, sequential combination therapy, and selected cancer indications.

The patent is primarily a method-of-use and product-package patent. It does not broadly claim every sirolimus formulation, every albumin nanoparticle, or every use of rapamycin. Its commercial relevance depends on whether a competing product uses the claimed albumin-coated nanoparticle architecture and falls within the claimed dose and size parameters.

What drug and technology does US Patent 8,911,786 cover?

US 8,911,786 covers nanoparticle formulations in which rapamycin or a rapamycin derivative is associated with, and coated by, albumin. The claims are directed to cancer treatment rather than general drug delivery.

The patent corresponds to the technology underlying albumin-bound rapamycin, commonly referred to as nab-rapamycin or nab-sirolimus. A later commercial product using this platform is Fyarro, an intravenous formulation of sirolimus approved by the FDA for adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor, or PEComa.[1]

The claimed technology has four principal technical elements:

Claim element	Scope
Active ingredient	Rapamycin or a derivative
Carrier	Albumin, with human serum albumin expressly covered
Particle structure	Rapamycin-containing nanoparticles coated with albumin
Particle size	Average diameter no greater than about 200 nm
Dose	About 54 mg to about 180 mg; some claims narrow this to about 75 mg to about 100 mg
Use	Treatment of cancer in a human individual
Administration	Intravenous, intraarterial, intraperitoneal, intravesicular, subcutaneous, or intrathecal routes

The claims do not require the cancer to be PEComa. The listed indications include multiple myeloma, pancreatic cancer, brain cancer, prostate cancer, lung cancer, melanoma, breast cancer, bladder cancer, renal cell carcinoma, mesothelioma, neuroendocrine cancer, and plasmacytoma.

What are the independent claims in US 8,911,786?

Claims 1, 7, 8, and 9 are the principal independent claims.

Claim 1: cancer treatment method

Claim 1 requires:

1. A human cancer patient;
2. Administration of an effective amount of a composition;
3. Nanoparticles comprising rapamycin or a derivative and albumin;
4. Rapamycin or its derivative coated with albumin;
5. Rapamycin content of about 54 mg to about 180 mg; and
6. Average nanoparticle diameter of no more than about 200 nm.

This is the central therapeutic claim. A product must satisfy each limitation for literal infringement. A competing product using free sirolimus, a conventional emulsion, or a non-albumin nanoparticle would not literally meet the claim.

The phrase "about" gives the dose and particle-size limitations some numerical flexibility. The breadth of that flexibility would depend on the specification, prosecution history, expert evidence, and the court's claim-construction analysis. It does not eliminate the need to show that the accused product falls within the claimed ranges.

Claim 7: unit dosage form

Claim 7 covers a unit dosage form containing:

• The claimed albumin-coated rapamycin nanoparticles;
• About 54 mg to about 180 mg of rapamycin or derivative; and
• A pharmaceutically acceptable carrier.

This claim is important for commercial products supplied as vials or other defined dosage units. It can apply even when the accused product is not accompanied by a specific treatment instruction, although the precise infringement analysis would depend on the product configuration and claim construction.

Claim 8: kit claim

Claim 8 covers a kit containing:

• The albumin-coated rapamycin nanoparticles;
• The claimed dose range; and
• Instructions for treating cancer in a human.

The instruction component makes this claim particularly relevant to labeled commercial products. A package insert or prescribing information that directs use for cancer treatment could be relevant evidence for infringement.

Claim 9: combination-treatment method

Claim 9 requires:

1. The claimed albumin-bound rapamycin therapy; and
2. A second cancer therapy.

The second therapy may include chemotherapy, radiation, surgery, hormone therapy, gene therapy, bone marrow transplantation, stem-cell transplantation, targeted therapy, cryotherapy, ultrasound therapy, or immunotherapy.

The claim requires the rapamycin nanoparticle treatment and the second therapy to be used as part of the cancer-treatment regimen. Claim 14 expressly covers sequential administration. Claims 10 through 20 narrow the second therapy to chemotherapy and identify specific drug classes and agents, including perifosine and erlotinib.

How do the dependent claims narrow the patent?

The dependent claims create several narrower enforcement positions.

Claims	Limitation
2	Plasmacytoma
3	Multiple myeloma, pancreatic, brain, prostate, lung, melanoma, or breast cancer
4-5	Bladder cancer, renal cell carcinoma, mesothelioma, or neuroendocrine cancer; claim 5 narrows to bladder cancer
6, 15	Human serum albumin
10-11	Chemotherapy and specified chemotherapy classes
12-13	Specific cancer groups for combination therapy
14	Sequential administration
16	mTOR-pathway inhibitor
17-18	AKT inhibitor, specifically perifosine
19-20	Tyrosine kinase inhibitor, specifically erlotinib
21-22	Specified administration routes
23-26	Rapamycin, with or without human serum albumin
27-34	Bladder cancer, renal cell carcinoma, mesothelioma, or neuroendocrine cancer
35-37	Narrow dose range of about 75 mg to about 100 mg

Claims 23 through 37 are particularly relevant to a nab-sirolimus product because they narrow the active agent to rapamycin itself and, in some claims, to rapamycin combined with human serum albumin.

Claims 31 and 33 appear duplicative in the claim text provided. Both depend through the combination-therapy branch and identify the same group of cancers, with claim 32 and claim 34 narrowing to bladder cancer. The duplication does not materially expand the technical scope.

What is the strongest infringement theory under US 8,911,786?

The strongest literal infringement theory would involve a product with all of the following characteristics:

• Sirolimus or a rapamycin derivative;
• Human serum albumin as the nanoparticle coating or carrier;
• Albumin-bound nanoparticles;
• Average particle diameter of no more than approximately 200 nm;
• A marketed dose between approximately 54 mg and 180 mg;
• Cancer treatment instructions or use; and
• A package, vial, or kit corresponding to the claimed dosage form.

For Fyarro, the commercial dose is 100 mg/m² administered intravenously on days 1, 8, and 15 of a 28-day cycle.[1] Depending on body-surface area, an individual administered dose may fall within or outside the literal 54 mg to 180 mg range. The claims are therefore more commercially powerful where the relevant product configuration or effective amount is evaluated against the claimed range for a particular patient or dosage unit.

The 75 mg to 100 mg dependent range is narrower and may be more vulnerable to design-around through dose selection. The broader 54 mg to 180 mg range gives the patent greater practical coverage but may face stronger written-description, enablement, anticipation, or obviousness scrutiny depending on the asserted claim and prosecution record.

What formulations are protected by US 8,911,786?

The patent protects albumin-coated rapamycin nanoparticles rather than conventional oral rapamycin products.

Covered formulation characteristics

Potentially covered formulations include:

• Intravenous albumin-bound sirolimus;
• Nanoparticles containing rapamycin and human serum albumin;
• Unit-dose formulations containing approximately 54 mg to 180 mg of rapamycin;
• Kits containing the nanoparticle composition and cancer-treatment instructions; and
• Combination-treatment regimens using the nanoparticle composition with chemotherapy or another anticancer therapy.

Formulations outside the literal core

The following products may fall outside the literal wording, subject to detailed claim construction:

• Oral sirolimus tablets or solutions;
• Everolimus products without albumin-coated nanoparticles;
• Albumin-free sirolimus nanoparticles;
• Nanoparticles exceeding approximately 200 nm;
• Products containing less than approximately 54 mg or more than approximately 180 mg per relevant claimed amount;
• Liposomes or polymeric particles that do not use albumin as the coating; and
• Products using a different rapamycin derivative that does not satisfy the claim's "rapamycin or derivative" scope.

A non-infringement position would need to address both the structure and the numerical limitations. Changing only the administration route may not avoid the independent claims because claims 1 and 9 do not require a particular route. Route limitations appear in claims 21 and 22.

Is US 8,911,786 a formulation patent or a method-of-use patent?

It is both, but its primary protection is therapeutic use.

Claims 1, 2, 3, 4, 5, 9, and 12 through 37 are method claims. They require administration to a human individual for cancer treatment.

Claim 7 is a dosage-form claim. Claim 8 is a kit claim. These claims create product-facing protection that can be asserted against a marketed vial, kit, or package even when the method claims present proof-of-use issues.

The patent does not appear, from the claim set provided, to claim the manufacturing process used to prepare the nanoparticles. It claims the resulting composition, dosage form, kit, and use.

When does US Patent 8,911,786 lose exclusivity?

The patent was granted on December 16, 2014. Its expected expiration is in the late 2027 period based on the patent family's priority and statutory patent-term framework. A precise enforceable expiration date requires review of the face of the patent, any patent-term adjustment, terminal disclaimer, and related prosecution records.

The commercial exclusivity timeline is separate from patent expiration:

Event	Date or status
Patent grant	December 16, 2014
FDA approval of Fyarro	November 22, 2021
FDA product	Fyarro, nab-sirolimus
FDA indication	Adults with locally advanced unresectable or metastatic malignant PEComa
New chemical entity exclusivity	Not applicable to sirolimus as an established active ingredient
Orphan-drug exclusivity	Seven years from approval for the approved PEComa indication, subject to statutory exceptions
Expected patent expiry	Late 2027, subject to official term calculation

Fyarro's FDA approval was for PEComa, while the claims of US 8,911,786 list other cancers and do not expressly identify PEComa. That distinction matters. The patent may still be relevant to Fyarro because the independent claims are not limited to the enumerated cancer types, but an Orange Book use code and a patent's listed indication must be assessed separately.

What is the Orange Book status of US 8,911,786?

The Orange Book lists patents submitted by an NDA holder for an approved drug and associated with the drug's approved use or product characteristics.[2] A patent can be relevant to a product without appearing in the Orange Book, and Orange Book listing does not establish validity or infringement.

For Fyarro, the relevant regulatory questions are:

1. Whether US 8,911,786 was submitted for NDA 214383;
2. Whether FDA accepted it for listing;
3. Whether it is listed as a drug-substance, drug-product, or method-of-use patent;
4. Whether the listed use code corresponds to the approved PEComa indication; and
5. Whether the listing remains active.

The Orange Book must be checked against the current FDA entry for Fyarro. The regulatory significance is substantial because an ANDA applicant may need to submit a Paragraph IV certification for a listed patent or a Section VIII statement for a patent that does not cover the proposed labeling.[3]

Which companies are challenging US 8,911,786?

No specific Paragraph IV challenger or final court judgment concerning US 8,911,786 is established by the claim text alone.

A Paragraph IV challenge would be expected to focus on:

• Anticipation by prior albumin-bound rapamycin disclosures;
• Obviousness based on nab-particle technology combined with known sirolimus anticancer activity;
• Enablement of the broad cancer and dose ranges;
• Written description for the full set of cancer types and combination therapies;
• Indefiniteness of "about," "effective amount," "coated with albumin," and average particle size;
• Whether the claims properly cover the approved PEComa use; and
• Whether the accused product satisfies the nanoparticle-size and dose limitations.

A generic applicant seeking approval for the same albumin-bound sirolimus product would face a different pathway from a conventional oral sirolimus generic. The applicant would need to establish pharmaceutical equivalence or an appropriate abbreviated pathway for the reference product, and the formulation differences could require substantial FDA review.

What generic entry risks exist for Fyarro?

The primary entry risks are formulation-specific rather than ordinary oral-generic substitution.

Conventional sirolimus generics

Generic sirolimus tablets and oral solutions do not automatically substitute for Fyarro. They have different dosage forms, administration routes, pharmacokinetic profiles, excipients, and clinical uses. A conventional sirolimus ANDA would not necessarily practice the albumin-coated nanoparticle claims.

Follow-on nab-sirolimus products

A competing intravenous albumin-bound sirolimus product would present the highest patent risk. It could potentially trigger:

• Paragraph IV litigation;
• A declaration of non-infringement based on particle size or dose;
• Invalidity claims against the asserted patent;
• A carve-out of patented uses where legally available; or
• A launch after patent expiration.

Biosimilar risk

Biosimilar risk is low. Sirolimus is a small-molecule immunosuppressant, not a biologic. FDA approval would generally proceed through an ANDA or another small-molecule pathway rather than the Public Health Service Act biosimilar pathway.[3]

How strong is the patent estate for albumin-bound rapamycin?

The estate is strongest when the commercial product matches the claimed technology and dose. It is weaker against products that change the carrier, particle architecture, dose presentation, or approved use.

Risk factor	Assessment
Albumin-coated nanoparticle requirement	Strong product differentiator
Particle-size limitation	Potentially measurable and enforceable, but vulnerable to testing-method disputes
Dose range	Commercially relevant but vulnerable to dose or body-surface-area arguments
Broad cancer language	Expansive claim coverage, with possible enablement and written-description challenges
Combination-therapy claims	Broad treatment coverage, but proof of regimen and sequencing may be difficult
Human serum albumin claims	More specific and easier to map to a commercial formulation
Kit and unit-dose claims	Useful against marketed packaging and labeled products
Manufacturing protection	Limited in the claims provided
Biosimilar protection	Not applicable
Generic substitution risk	Lower for conventional oral sirolimus; higher for competing nab-sirolimus

The patent's scope is also affected by related family patents. A complete freedom-to-operate analysis must review continuation and divisional claims directed to composition, manufacturing, particle properties, dosing, and approved indications. US 8,911,786 should not be treated as the entire Fyarro estate.

How does US 8,911,786 compare with conventional sirolimus patents?

Issue	US 8,911,786	Conventional sirolimus patent
Active ingredient	Rapamycin or derivative	Usually sirolimus or derivative
Delivery system	Albumin-coated nanoparticles	Often oral tablet, solution, or general formulation
Particle size	No more than about 200 nm	Often not applicable
Administration	Multiple parenteral routes	Frequently oral
Dose	About 54 mg to 180 mg, with narrower claims at 75 mg to 100 mg	Product-specific
Disease scope	Cancer	Often transplant, immunosuppression, or general use
Regulatory relevance	Fyarro and nab-sirolimus	Rapamune and generic sirolimus
Biosimilar pathway	No	No
Main entry route	Follow-on formulation or Paragraph IV challenge	Conventional ANDA

The patent therefore creates differentiation between Fyarro and oral sirolimus products. A generic Rapamune product may not be a direct substitute for Fyarro and may not practice the asserted nanoparticle claims.

What litigation and settlement issues should investors monitor?

The key litigation indicators are:

1. Paragraph IV notices involving the Fyarro NDA;
2. ANDA litigation filed under the Hatch-Waxman statute;
3. Declaratory-judgment actions concerning listed patents;
4. Continuation patents issuing before the expected 2027 expiration;
5. Terminal disclaimers affecting family-member terms;
6. Licensing or settlement agreements involving nab-sirolimus;
7. FDA acceptance of a competing albumin-bound sirolimus application; and
8. Orange Book changes to patent listing or use codes.

No settlement agreement can be inferred from the patent claims. A settlement that permits an authorized generic or licensed launch could materially change the effective entry date even if the patent remains formally unexpired.

What is the revenue exposure from US 8,911,786?

The patent's revenue exposure is concentrated in Fyarro and any future albumin-bound rapamycin products. It does not directly control the entire sirolimus market.

Revenue exposure depends on:

• Fyarro's approved PEComa market;
• Expansion into other solid tumors;
• Clinical adoption of nab-sirolimus combinations;
• Whether the product receives additional indications;
• The number and strength of related patents;
• FDA approval of a competing nab-sirolimus formulation; and
• Any license or settlement that authorizes an earlier launch.

The broad cancer claims create potential leverage for development programs using the same platform. Their commercial value is greatest where clinical trials use doses within the claimed ranges and the product has particles no larger than approximately 200 nm.

Key Takeaways

• US 8,911,786 is directed to cancer treatment with albumin-coated rapamycin nanoparticles.
• The core numerical limitations are about 54 mg to 180 mg of rapamycin and an average particle diameter of no more than about 200 nm.
• Claims 7 and 8 extend protection to unit dosage forms and kits.
• Claim 9 covers combination therapy, including chemotherapy, immunotherapy, radiation, surgery, and targeted therapy.
• Human serum albumin, intravenous administration, rapamycin itself, and a 75 mg to 100 mg dose are narrower protected positions.
• Fyarro is the principal commercial product associated with albumin-bound sirolimus.
• Conventional oral sirolimus generics are not automatically direct substitutes and may not practice the patent.
• Biosimilar risk is not applicable because sirolimus is a small molecule.
• The expected patent-expiration period is late 2027, subject to the official patent-term calculation and related family rights.
• Paragraph IV risk is highest from a competing albumin-bound, intravenous sirolimus product rather than from an ordinary oral sirolimus generic.
• A complete market-exclusivity assessment requires review of the full patent family, Orange Book listing, terminal disclaimers, continuation patents, and any FDA-approved Fyarro labeling changes.

Frequently Asked Questions

Does US 8,911,786 cover oral sirolimus tablets?

Generally, no. The claims require nanoparticles comprising rapamycin or a derivative and albumin, with rapamycin coated by albumin and a particle-size limitation. Conventional oral sirolimus tablets do not ordinarily meet those structural limitations.

Does the patent cover Fyarro for PEComa?

Potentially, yes, because claim 1 is not limited to a particular cancer type. The approved Fyarro indication is PEComa, while the dependent claims identify other cancers. The definitive analysis depends on the full specification, prosecution history, product characteristics, and Orange Book listing.

Can a competitor avoid the patent by changing the dose?

Possibly, but changing dose alone may not avoid all claims. The broader claims cover approximately 54 mg to 180 mg, while claims 35 through 37 narrow the range to approximately 75 mg to 100 mg. Related patents may impose separate constraints.

Is an albumin-bound everolimus product covered?

It may be outside the literal scope if the claims are limited to rapamycin or derivatives that do not include the relevant everolimus structure under the claim construction. The answer would require chemical, specification, and prosecution-history analysis.

Does a competing nanoparticle larger than 200 nm avoid infringement?

It may avoid literal infringement of the claims requiring an average diameter of no more than about 200 nm. The result depends on the measured average, the testing methodology, the meaning of "about," and whether any related patent claims omit or alter the particle-size limitation.

Sources:

1. U.S. Food and Drug Administration. (2021). Fyarro (sirolimus protein-bound particles for injectable suspension) prescribing information. FDA.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
3. U.S. Food and Drug Administration. (2024). Abbreviated new drug application and generic drug approval process. FDA.
4. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,911,786, methods of treating cancer using albumin-bound rapamycin. USPTO.
5. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, 98 Stat. 1585.

Drugs Protected by US Patent 8,911,786

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Aadi	FYARRO	sirolimus	POWDER;INTRAVENOUS	213312-001	Nov 22, 2021		RX	Yes	Yes	8,911,786		Y			TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED UNRESECTABLE OR METASTATIC MALIGNANT PERIVASCULAR EPITHELIOID CELL TUMOR (PECOMA)

Foreign Priority and PCT Information for Patent: 8,911,786

PCT Information
PCT Filed	March 07, 2008	PCT Application Number:	PCT/US2008/003096
PCT Publication Date:	September 12, 2008	PCT Publication Number:	WO2008/109163

International Family Members for US Patent 8,911,786

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008223334
Brazil	PI0808635
Canada	2680207
Canada	3006137