US Patent 9,511,046: Scope, Expiration, Abraxane Coverage, and Generic Entry Risk

US Patent No. 9,511,046 protects a biomarker- and disease-subgroup-directed method for treating metastatic or locally advanced pancreatic cancer with albumin-bound paclitaxel nanoparticles plus gemcitabine. The patent does not broadly cover every use of Abraxane or every paclitaxel-gemcitabine regimen. Its enforceable scope depends on proving the claimed patient-selection factor, combination therapy, dosing and formulation limitations where applicable.

The patent is associated with the Abraxane pancreatic-cancer regimen developed by Abraxis BioScience and later commercialized through Celgene and Bristol Myers Squibb. Its principal commercial significance is a potential method-of-use barrier against a generic or competing albumin-bound paclitaxel product carrying pancreatic-cancer labeling.

What does US Patent 9,511,046 cover?

The patent covers treating a human patient with metastatic or locally advanced pancreatic cancer using two active treatments:

An albumin-bound nanoparticle composition comprising paclitaxel.
Gemcitabine.

The patient must be selected based on at least one specified clinical characteristic:

Liver metastasis.
More than three metastatic sites.
Primary tumor located in the head of the pancreas.
Serum CA19-9 level of at least 59 times the upper limit of normal.

Claim 1 is the controlling independent claim. The other claims narrow the method by adding cancer type, patient condition, formulation, administration route, dose, schedule and selection requirements.

Core claim elements

Claim element	Requirement in claim 1	Commercial significance
Disease	Metastatic or locally advanced pancreatic cancer	Excludes non-pancreatic cancers and generally excludes earlier-stage disease
Patient	Human individual	Excludes veterinary use
First treatment	Composition containing paclitaxel nanoparticles and albumin	Targets albumin-bound paclitaxel products such as Abraxane
Second treatment	Gemcitabine	Requires combination therapy
Patient selection	At least one of four clinical characteristics	Creates the principal narrowing limitation
Treatment purpose	Treating the specified pancreatic cancer	Supports method-of-use enforcement

The phrase "at least one" is important. A patient need not satisfy all four selection criteria under claim 1. A qualifying patient with liver metastasis can fall within the claim even if the patient has fewer than four metastatic sites, a non-head primary tumor and a lower CA19-9 level.

How narrow is the claim scope?

The independent claim is narrower than a general claim covering albumin-bound paclitaxel plus gemcitabine for pancreatic cancer.

A practicing physician or product sponsor would generally need to establish four categories of infringement risk:

The patient has metastatic or locally advanced pancreatic cancer.
The patient receives albumin-bound paclitaxel nanoparticles and gemcitabine.
The patient satisfies at least one claimed selection criterion.
The relevant party has the required involvement in treatment, prescribing, labeling, distribution or inducement.

Claims 2 through 17 add limitations but do not materially broaden claim 1. Claims 21 through 28 separately recite each of the four selection criteria. Claims 29 through 34 narrow the albumin-to-paclitaxel ratio to approximately 9:1.

Claim architecture

Claim group	Subject matter
Claim 1	Combination treatment for selected pancreatic-cancer patients
Claims 2-4	Adenocarcinoma, KPS 70-80 and high hENT1
Claims 5-12	Intravenous administration and nanoparticle formulation
Claims 13-16	Gemcitabine dose, schedule and intravenous administration
Claim 17	First-line treatment
Claims 18-19	Patient selection and diagnostic determination
Claims 20, 22, 24, 26, 28	Formulation limitations combined with specific selection criteria
Claims 21, 23, 25, 27	Separate patient-selection alternatives
Claims 29-34	Approximately 9:1 albumin-to-paclitaxel ratio

What formulation is protected by US 9,511,046?

The formulation limitations describe albumin-bound paclitaxel nanoparticles with several characteristics associated with nab-paclitaxel:

Paclitaxel associated with or coated by albumin.
Human serum albumin as the albumin component.
Average nanoparticle diameter of no greater than approximately 200 nm.
Albumin-to-paclitaxel weight ratio of approximately 9:1 or less.
Intravenous administration.
Paclitaxel dose of approximately 50 mg/m² to 200 mg/m², with 125 mg/m² recited in claim 7.

These limitations are most commercially relevant to albumin-bound paclitaxel products rather than conventional solvent-based paclitaxel formulations. Conventional paclitaxel in Cremophor-based formulations would not ordinarily satisfy the nanoparticle and albumin limitations.

Dose and schedule limitations

The preferred regimen reflected in the dependent claims is:

Product or agent	Dose	Schedule
Albumin-bound paclitaxel	125 mg/m²	Weekly, three of four weeks
Gemcitabine	1,000 mg/m²	Weekly, three of four weeks

The claims also include broader dose ranges:

Paclitaxel: approximately 50-200 mg/m².
Gemcitabine: approximately 500-2,000 mg/m².

The claimed schedule corresponds to the regimen evaluated in the MPACT study and reflected in the FDA-approved Abraxane labeling for metastatic pancreatic adenocarcinoma when used with gemcitabine (FDA, 2024a).

What patient-selection criteria are protected?

The patent has four principal clinical-selection pathways.

Liver metastasis

Claims 1, 18, 21 and 22 cover selection based on liver metastasis. A regimen administered to a pancreatic-cancer patient with documented liver metastases presents the clearest risk under this branch if the other treatment and formulation elements are present.

More than three metastatic sites

Claims 1, 18, 23 and 24 cover patients with more than three metastatic sites. The wording requires more than three, meaning at least four sites.

Primary tumor in the head of the pancreas

Claims 1, 18, 25 and 26 cover patients whose primary pancreatic tumor is located in the head of the pancreas.

CA19-9 level at least 59 times the upper limit of normal

Claims 1, 18, 27 and 28 cover a very high serum CA19-9 level. The threshold is expressed as "59×ULN," which creates an important construction and proof issue. The relevant ULN would ordinarily depend on the assay and laboratory used for the patient.

The CA19-9 criterion is commercially narrower than the liver-metastasis criterion because many pancreatic-cancer patients have liver metastases, while comparatively few patients will have a CA19-9 result at least 59 times the laboratory upper limit of normal.

When does US Patent 9,511,046 expire?

The patent has a statutory term projected from a December 2011 priority date. On that basis, the nominal expiration date is approximately December 2031, subject to any patent-term adjustment, terminal disclaimer or other USPTO-record term calculation.

Event	Approximate date or status
Earliest claimed priority	December 2011
US grant	December 6, 2016
Patent number	US 9,511,046 B2
Nominal 20-year term	Approximately December 2031
PTA/PTE effect	Must be confirmed from the current USPTO patent record
Patent type	Method-of-treatment patent

The patent’s expiration should not be treated as the only relevant exclusivity date. FDA regulatory exclusivity, other Abraxane patents and separate formulation or manufacturing rights can create different barriers.

What is the FDA and Orange Book status?

Abraxane is FDA-approved as paclitaxel protein-bound particles for injectable suspension. The pancreatic-cancer indication is for use in combination with gemcitabine for first-line treatment of metastatic adenocarcinoma of the pancreas (FDA, 2024a).

US 9,511,046 is a method-of-use patent associated with the pancreatic-cancer use of albumin-bound paclitaxel. The Orange Book should be reviewed using the current FDA patent-listing file because listed patent status can change through delisting, expiration updates, corrections or regulatory submissions.

FDA regulatory position

Issue	Status
Reference product	Abraxane
Active ingredient	Paclitaxel
Delivery system	Albumin-bound nanoparticles
FDA pathway for generic competition	ANDA under section 505(j)
Pancreatic indication	Approved in combination with gemcitabine
Biologic status	Not a biologic
Biosimilar pathway	Not applicable
Method-of-use risk	Relevant if a generic label includes or induces the patented use

Because Abraxane is a drug product rather than a biologic, competitors do not use the biosimilar pathway. A competing product would generally pursue an ANDA, a 505(b)(2) application or, depending on product characteristics, another drug-approval pathway.

How does the patent compare with core Abraxane formulation patents?

US 9,511,046 is primarily a clinical-use patent. It should be analyzed separately from patents covering the nanoparticle composition itself.

Patent category	Typical subject matter	Risk after expiration
Composition patent	Albumin-bound paclitaxel nanoparticles	Direct product-manufacture barrier
Manufacturing patent	Preparation, particle-size control and formulation process	Process and supply-chain barrier
Method-of-use patent	Pancreatic-cancer combination treatment and patient selection	Labeling and induced-infringement barrier
Regulatory exclusivity	FDA approval-related exclusivity	Regulatory delay independent of patent validity
Trade secret	Process parameters, scale-up and quality control	Non-public manufacturing barrier

The 9:1 albumin-to-paclitaxel limitation is narrower than a general composition claim because it requires a specified ratio. A generic product may avoid particular dependent claims if its formulation falls outside the claimed ratio, particle-size range or albumin configuration. That does not necessarily avoid claim 1, which does not expressly require every dependent formulation limitation.

Which companies own or commercialize the relevant rights?

The patent estate originated with Abraxis BioScience, the developer of Abraxane. Celgene acquired Abraxis in 2010. Bristol Myers Squibb acquired Celgene in 2019 and became the parent company of the Abraxane business.

Company	Role
Abraxis BioScience	Original developer and historical patent owner
Celgene	Acquirer and later commercial owner
Bristol Myers Squibb	Current corporate parent following Celgene acquisition
Generic manufacturers	Potential ANDA applicants or approved competitors

The ownership chain should be checked in the USPTO assignment database before relying on current title for licensing, enforcement or diligence. The patent face and assignment records may show different historical assignees.

What Paragraph IV challenges and generic entry risks exist?

An ANDA applicant seeking approval before patent expiration could:

Certify that no listed patent exists.
File a Paragraph III certification and await patent expiration.
File a Paragraph IV certification asserting that the patent is invalid, unenforceable or not infringed.
Submit a section viii statement to omit a patented method from the proposed labeling, where FDA requirements permit.

For US 9,511,046, the principal Paragraph IV arguments would likely focus on claim scope and validity rather than simple product identity.

Likely non-infringement positions

A generic sponsor could argue that:

Its product is not an albumin-bound nanoparticle composition within the claim.
The proposed label omits the pancreatic-cancer use.
The label does not identify or encourage treatment of patients meeting the claimed criteria.
The formulation does not satisfy the claimed particle-size or albumin-ratio limitations.
The product is not administered with gemcitabine under the claimed regimen.

A section viii strategy would be commercially difficult if the FDA-approved reference labeling includes the pancreatic indication and the generic seeks the same indication. It becomes more viable if the sponsor can carve out the patented method without omitting a non-patented indication or creating a labeling inconsistency.

Likely validity positions

Potential validity challenges include:

Obviousness based on the known Abraxane-gemcitabine pancreatic regimen.
Obviousness of selecting patients based on liver metastasis, tumor location or disease burden.
Written-description support for the specific 59×ULN CA19-9 threshold.
Enablement of the full range of patient-selection criteria and dosing combinations.
Indefiniteness involving terms such as "high level of hENT1," "effective amount" and "about."
Double-patenting issues involving related pancreatic-cancer applications.

The patent’s strength differs by claim. Claims tied to the clinical regimen may face prior-art pressure, while claims combining the regimen with specific subgroup selection and formulation characteristics may present a more complex obviousness analysis.

What litigation or settlement issues affect the patent?

A complete litigation assessment requires current PACER and PTAB records. The relevant litigation questions are:

Whether an ANDA applicant has served a Paragraph IV notice.
Whether the patent owner filed a Hatch-Waxman action within 45 days.
Whether FDA approval was subject to a 30-month stay.
Whether the parties settled and whether the settlement has a licensed entry date.
Whether the patent has been challenged in an inter partes review or post-grant proceeding.

A patent can remain listed and legally enforceable even if no public infringement case is pending. Conversely, a settlement may establish an authorized generic, license date or label restriction that is not apparent from the patent document alone.

No settlement date or final court judgment should be inferred solely from the patent grant or Orange Book listing.

How strong is the patent estate for Abraxane pancreatic cancer treatment?

The estate has moderate commercial strength for the specific labeled use, but its risk is concentrated.

Strengths

The patent targets the approved Abraxane-gemcitabine pancreatic regimen.
Claims 21, 23, 25 and 27 create separate selection branches.
The liver-metastasis branch may cover a commercially meaningful patient population.
Dependent claims capture the conventional 125 mg/m² and 1,000 mg/m² dosing framework.
Formulation claims may complicate attempts to design around the product.

Weaknesses

Claim 1 requires proof of a patient-selection fact in addition to combination treatment.
The claims do not cover every pancreatic-cancer use of albumin-bound paclitaxel.
The four selection criteria may be vulnerable to obviousness arguments based on clinical-trial subgroup analysis.
The CA19-9 threshold may create written-description and indefiniteness questions.
A generic may seek a label that omits the patented use.
Conventional paclitaxel formulations fall outside the albumin-bound nanoparticle limitation.

What generic launch scenarios exist?

Scenario	Commercial result
Paragraph III certification	Entry generally waits until relevant patent expiration
Successful Paragraph IV challenge	Entry may occur before nominal 2031 expiration, subject to other patents
Section viii carve-out	Generic launches without the patented pancreatic indication, if FDA accepts the carve-out
Settlement license	Entry occurs on the negotiated date, potentially with authorized-generic terms
Alternative formulation	Competitor avoids selected formulation claims but must address claim 1 and other patents
Competing non-nab-paclitaxel regimen	No direct infringement of the albumin-bound nanoparticle claims, but clinical substitution risk increases

The most credible early-entry route is a successful Paragraph IV challenge or a permitted label carve-out. A formulation redesign alone may not avoid claim 1 because claim 1 broadly requires a composition comprising paclitaxel nanoparticles and albumin, without reciting all of the narrower ratio and size limitations.

What are the geographic and manufacturing barriers?

US 9,511,046 has territorial effect only in the United States. It does not directly block use, sale or manufacture outside the US, although parallel patents may exist in Europe, Japan, Canada, China or other jurisdictions.

Manufacturing risk extends beyond the patent claims. Albumin-bound paclitaxel products require control over:

Particle-size distribution.
Albumin-paclitaxel association.
Residual solvent and impurity levels.
Sterility and injectable-product quality.
Reproducible scale-up.
Comparability to the reference product for ANDA purposes.

A competitor may avoid the claimed 9:1 ratio while still facing other composition, process or regulatory barriers. The patent landscape therefore requires a family-level review rather than analysis of US 9,511,046 in isolation.

How does Abraxane compare with competing pancreatic-cancer regimens?

Regimen	Principal sponsor or developers	Relevance to US 9,511,046
Abraxane plus gemcitabine	Bristol Myers Squibb/Celgene lineage	Directly implicated
FOLFIRINOX	Multiple companies and generic suppliers	Outside the claimed paclitaxel regimen
Modified FOLFIRINOX	Multiple suppliers	Competitive substitution risk
NALIRIFOX	Ipsen and partners	Competes clinically but does not practice the claimed combination
Gemcitabine alone	Generic suppliers	Does not satisfy the required combination
Conventional paclitaxel plus gemcitabine	Multiple suppliers	Generally lacks albumin-bound nanoparticle limitation

The patent therefore protects a defined treatment platform rather than the entire first-line metastatic pancreatic-cancer market.

Key Takeaways

US 9,511,046 is a method-of-treatment patent for selected pancreatic-cancer patients receiving albumin-bound paclitaxel nanoparticles plus gemcitabine.
Claim 1 requires at least one of four selection criteria: liver metastasis, more than three metastatic sites, tumor in the pancreatic head or CA19-9 at least 59×ULN.
Claims 21-28 separately protect each selection route.
The dependent claims add Abraxane-associated formulation characteristics, including particles no greater than about 200 nm and an albumin-to-paclitaxel ratio of about 9:1 or less.
The nominal patent term runs to approximately December 2031, subject to the USPTO term record.
The patent is relevant to Abraxane’s FDA-approved pancreatic-cancer use and potential ANDA Paragraph IV litigation.
The main generic strategies are a Paragraph IV challenge, a section viii label carve-out or a product and labeling design-around.
The patent does not cover conventional paclitaxel, gemcitabine monotherapy, FOLFIRINOX, NALIRIFOX or every use of albumin-bound paclitaxel.
Biosimilar analysis is not applicable because Abraxane is regulated as a drug, not a biologic.
Patent strength is highest against a product seeking the same pancreatic-cancer indication, the same combination regimen and labeling directed to the claimed patient subgroups.

FAQs

Does US Patent 9,511,046 cover all Abraxane uses?

No. It covers a specific pancreatic-cancer combination method with patient-selection limitations. It does not broadly cover every Abraxane indication or every use of albumin-bound paclitaxel.

Can a generic sell albumin-bound paclitaxel without infringing this patent?

Potentially. The result depends on the proposed label, product formulation, combination with gemcitabine and whether the product or label induces treatment of patients meeting a claimed selection criterion.

Is a high CA19-9 level required for every patient covered by the patent?

No. Claim 1 uses alternative criteria. Liver metastasis, more than three metastatic sites, pancreatic-head location and CA19-9 of at least 59×ULN are separate selection routes.

Does the patent cover FOLFIRINOX or NALIRIFOX?

No. Those regimens do not use the claimed paclitaxel nanoparticle and gemcitabine combination.

Is US 9,511,046 a biologic patent requiring biosimilar litigation?

No. The patent concerns a drug product and method of treatment. Competitive products would generally use an ANDA or another drug-approval pathway rather than the biosimilar pathway.

References

U.S. Patent No. 9,511,046 B2. (2016). Methods of treating pancreatic cancer. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024a). Abraxane: Prescribing information. Bristol Myers Squibb.
U.S. Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (2024c). Orange Book patent and exclusivity information. Center for Drug Evaluation and Research.
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Nicastri, G., Engebretson, K., Houdeshell, S., & Lovato, J. (2013). Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. New England Journal of Medicine, 369(18), 1691-1703.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bristol-myers	ABRAXANE	paclitaxel	POWDER;INTRAVENOUS	021660-001	Jan 7, 2005	AB	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial			Y		⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013203699	⤷ Start Trial
Brazil	112015016681	⤷ Start Trial
Canada	2897589	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,511,046