United States Patent 9,101,543: Scope, Claims, Expiration, and Patent Landscape for Abraxane Plus Gemcitabine

US Patent No. 9,101,543 protects a treatment method for pancreatic cancer using intravenous albumin-bound paclitaxel nanoparticles, commonly known as nab-paclitaxel or Abraxane, in combination with gemcitabine. The independent claim requires the use of both drugs, a nanoparticle diameter of no greater than 200 nm, intravenous administration, and treatment of a human pancreatic-cancer patient. The patent does not broadly claim paclitaxel nanoparticles, gemcitabine, or pancreatic-cancer treatment alone.

The commercial risk is concentrated in the combination regimen used for advanced or metastatic pancreatic adenocarcinoma: nab-paclitaxel administered before gemcitabine, typically on days 1, 8, and 15 of a 28-day cycle, at 125 mg/m² of paclitaxel followed by 1,000 mg/m² of gemcitabine.

What does US Patent 9,101,543 protect?

US 9,101,543 protects a method-of-treatment regimen rather than a composition. The core claim requires all of the following:

Required element	Claim requirement
Patient	Human individual in need of treatment
Disease	Pancreatic cancer
Paclitaxel product	Nanoparticles comprising paclitaxel coated with albumin
Particle size	Average diameter no greater than 200 nm
Route	Intravenous administration
Combination partner	Gemcitabine
Dosing	Effective amounts of both agents

The broadest enforceable claim is claim 1. A product or treatment can avoid literal infringement if one required element is absent, although the doctrine of equivalents could remain relevant in litigation.

The patent is directed to the clinical use of albumin-bound paclitaxel with gemcitabine. It does not require the brand name Abraxane. A non-branded or alternative-source formulation could fall within the claim if it satisfies the nanoparticle, albumin-coating, particle-size, route, and combination limitations.

How does claim 1 define the protected pancreatic-cancer regimen?

Claim 1 has four principal limitations.

First, the patient must have pancreatic cancer. Claims 21 and 41 narrow the disease to metastatic or advanced pancreatic cancer, respectively. Claim 1 itself is not expressly limited to metastatic disease.

Second, the paclitaxel must be present in albumin-coated nanoparticles. Conventional solvent-based paclitaxel formulations, such as paclitaxel injection products using Cremophor EL, do not satisfy this limitation.

Third, the nanoparticle composition must have an average diameter of no greater than 200 nm. The claim uses an average-size limitation, not an absolute maximum-size limitation for every particle.

Fourth, both nab-paclitaxel and gemcitabine must be administered intravenously in effective amounts. A regimen using oral gemcitabine, intraperitoneal gemcitabine, or another nonintravenous route would not literally satisfy claim 1.

The claim does not expressly require a particular order, dose, weekly schedule, albumin species, or albumin-to-paclitaxel ratio. Those restrictions appear in dependent claims.

Which dependent claims create the principal infringement risk?

The dependent claims progressively capture the clinically used regimen.

Claims	Added limitation	Commercial relevance
2, 22	Sequential administration	Captures separate sequential dosing
3, 23	Nanoparticle composition before gemcitabine	Tracks the approved clinical sequence
4	Both drugs administered weekly	Broad weekly schedule
5, 31	Administration three out of four weeks	Captures the standard 28-day schedule
6-9, 24-27, 32-35	Paclitaxel dose ranges ending at about 125 mg/m²	Captures the approved nab-paclitaxel dose
10, 28, 36	Gemcitabine dose of about 1,000 to 2,000 mg/m²	Captures the standard 1,000 mg/m² dose
11	Human serum albumin	Narrows the albumin component
12-15	Albumin-to-paclitaxel ratio, ending at about 9:1	Captures the Abraxane formulation profile
16	Sterile filterable composition	Adds a manufacturing and product characteristic
17-20	Repeats albumin-to-paclitaxel ratio limitations	Provides alternative dependent-claim coverage
21	Metastatic pancreatic cancer	Targets the principal approved indication
41	Advanced pancreatic cancer	Extends coverage to advanced disease

Claims 21 through 40 create a dense metastatic-pancreatic-cancer claim set. A regimen using 125 mg/m² nab-paclitaxel before 1,000 mg/m² gemcitabine on three of four weeks is likely to fall within several claims simultaneously.

What formulations are protected by US 9,101,543?

The patent covers a formulation with paclitaxel incorporated into or associated with albumin-coated nanoparticles. The relevant formulation characteristics are:

Paclitaxel as the active drug.
Albumin coating or albumin-associated nanoparticle structure.
Average particle diameter of 200 nm or less.
Potentially human serum albumin under claims 11-15.
Albumin-to-paclitaxel weight ratios ranging from approximately 1:1 to 18:1 under claims 12-20.
A narrower 4:1 to 10:1 range.
A specific approximately 9:1 ratio.
Sterile filterability under claim 16.

The formulation limitations should be distinguished from the method limitations. A composition manufacturer may not infringe solely by making or selling the nanoparticle product if the asserted claims are limited to administration methods. Liability may instead arise through induced infringement, contributory infringement, or direct method infringement by a treatment provider, depending on the facts and applicable law.

The 9:1 ratio is particularly relevant because Abraxane is generally described as containing paclitaxel and human albumin in an approximate 1:9 paclitaxel-to-albumin relationship, equivalent to an albumin-to-paclitaxel ratio of approximately 9:1. The claim language uses "about," which gives the limitation a numerical range requiring evidence concerning formulation composition and analytical methods.

How does US 9,101,543 compare with broader Abraxane patents?

The Abraxane patent estate has several distinct layers. US 9,101,543 is primarily a pancreatic-cancer combination-use patent.

Patent layer	Protected subject matter	Relevance to US 9,101,543
Nanoparticle composition patents	Albumin-bound paclitaxel particles and formulation characteristics	Can cover the product independent of pancreatic-cancer use
Manufacturing patents	Preparation, homogenization, drying, sterilization, and particle-size control	Can create manufacturing barriers
Method-of-use patents	Treatment of specific cancers with nab-paclitaxel	Includes the pancreatic-cancer/gemcitabine regimen
Combination patents	Nab-paclitaxel used with gemcitabine or other agents	Directly overlaps the focal patent
Regulatory exclusivity	FDA orphan-drug or new-drug exclusivity	Separate from patent rights
Trademark and trade-secret rights	Abraxane branding and manufacturing know-how	Relevant to commercial substitution but not claim scope

US Patent No. 7,820,788 is commonly associated with albumin-bound paclitaxel nanoparticle technology and provides an example of the composition-patent layer. US 9,101,543 is narrower in product scope but stronger against a competitor using the approved pancreatic-cancer regimen because it combines the formulation and treatment-use requirements in one claim set. The claims can therefore remain relevant even after broader composition claims expire, subject to the actual term and any later patent-term adjustments.[2]

When does US Patent 9,101,543 lose exclusivity?

The patent issued on August 11, 2015. Its effective term is governed by the earliest applicable nonprovisional or international filing date, not simply by the issue date. The patent family claims priority to an earlier 2008 filing, while patent-term calculation generally depends on the earliest effective nonprovisional filing in the chain under 35 U.S.C. § 154.[1]

The expected expiration is in the 2028-2029 period, subject to the official USPTO patent-term adjustment calculation and any applicable patent-term extension. The patent record should be evaluated through USPTO Patent Center and the Orange Book patent listing for the definitive expiration date.[1,3]

Milestone	Date or status
Earliest family priority	2008 priority filing
Patent issued	August 11, 2015
Patent term basis	Earliest effective nonprovisional or PCT filing
Expected statutory expiry	2028-2029 range, before any applicable adjustment
Pediatric extension	Not established from the supplied claim record
FDA product status	Abraxane remains an FDA-approved paclitaxel protein-bound particle product
Generic status	FDA-approved generic versions of paclitaxel protein-bound particles have entered or sought entry, subject to patent and regulatory restrictions

Patent expiration and FDA exclusivity are separate. FDA approval of a generic formulation does not by itself authorize a use protected by an unexpired method-of-use patent. An ANDA applicant may seek approval through a section viii statement that omits a patented indication, but the commercial label, proposed prescribing information, and product instructions must be assessed carefully.[3,4]

What is the Orange Book status of US 9,101,543?

US 9,101,543 is relevant to the FDA-approved Abraxane indication for metastatic adenocarcinoma of the pancreas in combination with gemcitabine. The FDA approved Abraxane for this indication in September 2013 after the phase 3 MPACT trial showed improved overall survival compared with gemcitabine alone.[4,5]

An Orange Book listing for a method-of-use patent can identify a specific approved-use code rather than the entire product. The practical significance is that an ANDA applicant may be required to address the listed patent through:

A paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed.
A section viii statement carving out the patented use.
A certification that the patent has expired.
A statement that the patent is not listed or does not apply to the proposed product, depending on the regulatory posture.

The Orange Book listing does not determine ultimate infringement. It creates an FDA patent-certification framework and can trigger a 30-month stay when the NDA holder or patent owner files an infringement action within the statutory period after receiving a paragraph IV notice.[3]

Which companies are most exposed to this patent?

The highest-risk parties are companies seeking to sell paclitaxel protein-bound particles for pancreatic cancer while retaining the combination regimen on their labeling or promotional materials.

Party type	Risk profile
Generic nab-paclitaxel applicant	High if seeking an unrestricted pancreatic-cancer label
Generic applicant using a section viii carve-out	Lower regulatory risk, but physician-use and inducement issues remain
Hospital or oncology practice	Potential method-infringement exposure when administering the claimed regimen
Active pharmaceutical ingredient supplier	Usually lower direct risk unless it induces the patented use
Biosimilar developer	Not applicable in the conventional sense because paclitaxel is a small-molecule drug, not a biologic
Alternative albumin-nanoparticle manufacturer	High if its product meets the particle and albumin limitations
Gemcitabine manufacturer	Generally low, unless it actively promotes the patented combination

The biosimilar pathway is not the principal competitive framework. Abraxane is a small-molecule drug product regulated through the ANDA pathway, although its complex nanoparticle formulation can create pharmaceutical-equivalence, bioequivalence, analytical, and manufacturing challenges.[4]

What Paragraph IV challenges and litigation issues affect the patent?

A paragraph IV challenge would likely attack one or more of the following:

Invalidity for lack of novelty or obviousness based on prior clinical use of paclitaxel and gemcitabine.
Written-description or enablement issues concerning the broad particle-size, dose, and ratio ranges.
Indefiniteness involving "about," "effective amount," "coated with albumin," or "average diameter."
Noninfringement based on particle size, albumin association, administration order, route, or label carve-out.
Lack of induced infringement where the generic label omits the patented pancreatic-cancer use.

The strongest validity issue is likely obviousness. Before the relevant priority date, gemcitabine was an established pancreatic-cancer treatment and paclitaxel had extensive oncology use. The patent owner’s response would rely on the specific albumin-bound nanoparticle formulation, the claimed sequence, the dosing regimen, and the clinical evidence supporting improved outcomes.

The strongest infringement issue is product characterization. A generic manufacturer could dispute whether its particles are "coated with albumin," whether the average diameter is no greater than 200 nm, or whether its albumin-to-paclitaxel ratio falls within the claimed range. Those issues require technical testing of the accused product and cannot be resolved from the label alone.

The supplied patent information does not identify a final judgment, settlement, or license specific to US 9,101,543. Any current litigation assessment should rely on the USPTO, FDA Orange Book, PACER, and publicly filed settlement documents rather than the patent text itself.

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

The estate is strongest when several rights operate together:

Composition patents covering albumin-bound paclitaxel particles.
Manufacturing patents covering particle production and sterile processing.
Method-of-use patents covering pancreatic-cancer treatment.
FDA patent listings tied to the approved combination indication.
Clinical evidence supporting the claimed dose and sequence.

US 9,101,543 alone is narrower than a composition patent because it requires pancreatic cancer, intravenous administration, and gemcitabine. Its commercial value is nevertheless significant because the claimed regimen corresponds closely to the approved Abraxane treatment protocol.

The estate is weaker against:

A generic label that excludes pancreatic cancer.
A formulation using non-albumin nanoparticles.
A treatment using conventional solvent-based paclitaxel.
A regimen using a different drug combination.
A nonintravenous administration route.
A product whose tested particle size or albumin ratio falls outside the claim scope.

What generic launch scenarios exist?

Scenario 1: Full-label generic launch

A generic manufacturer obtains approval for pancreatic-cancer treatment in combination with gemcitabine and defeats or avoids the listed patent. This creates the highest substitution and price-pressure risk.

Scenario 2: Skinny-label launch

The applicant removes the patented pancreatic-cancer indication under a section viii statement while retaining other approved uses. The product may still be used off-label in pancreatic cancer, but promotional conduct and labeling details become central to induced-infringement risk.

Scenario 3: Delayed launch after patent expiry

The applicant accepts the patent term and launches after expiration. This avoids litigation risk but delays market entry and may reduce first-mover value.

Scenario 4: Formulation redesign

A competitor develops a particle system that does not use albumin coating or falls outside the claimed particle-size and ratio limitations. This approach may avoid US 9,101,543 but could encounter separate composition or manufacturing patents.

Key Takeaways

US 9,101,543 is a pancreatic-cancer method-of-treatment patent covering intravenous albumin-bound paclitaxel nanoparticles plus gemcitabine.
Claim 1 requires nanoparticles with an average diameter of no greater than 200 nm and intravenous administration of both agents.
Claims 3, 5, 9, 10, 21, 23, 27, 28, 30, 31, and 41 are particularly relevant to the commercial Abraxane regimen.
The standard 125 mg/m² nab-paclitaxel followed by 1,000 mg/m² gemcitabine schedule administered three out of four weeks is closely aligned with the dependent claims.
The patent is a method patent, not a general composition patent for paclitaxel nanoparticles.
Its expected expiration is in the 2028-2029 period, subject to official patent-term adjustment and any applicable extension.
Generic competition is governed by the ANDA and paragraph IV framework, not the biosimilar pathway.
The primary design-around options are a label carve-out, a non-albumin formulation, a different administration route, or a formulation outside the claimed particle-size and albumin-ratio limitations.
The patent’s commercial strength depends on the remaining term of related Abraxane composition and manufacturing patents.

FAQs About US Patent 9,101,543

Does US 9,101,543 cover Abraxane by itself?

No. The principal claims require administration of nab-paclitaxel together with gemcitabine to a human patient with pancreatic cancer.

Does the patent cover gemcitabine monotherapy?

No. The claims require administration of both the albumin-bound paclitaxel nanoparticle composition and gemcitabine.

Does conventional paclitaxel infringe US 9,101,543?

Not literally if the product does not comprise albumin-coated paclitaxel nanoparticles with an average diameter of no greater than 200 nm.

Is a 125 mg/m² nab-paclitaxel dose within the patent claims?

Yes. Claims 9, 27, and 35 specifically recite about 125 mg/m² paclitaxel in the nanoparticle composition.

Can a generic manufacturer launch with pancreatic cancer removed from its label?

Potentially, through a section viii approach, but the final risk depends on the approved labeling, prescribing information, promotional conduct, and the scope of all remaining Orange Book-listed patents.

References

United States Patent and Trademark Office. (2015). U.S. Patent No. 9,101,543, methods of treating pancreatic cancer using nanoparticle compositions.
United States Patent and Trademark Office. (2010). U.S. Patent No. 7,820,788, compositions and methods for delivery of therapeutic agents.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2013). FDA approves Abraxane plus gemcitabine for metastatic pancreatic cancer.
Von Hoff, D. D., Erban, J. K., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S., Ma, W. W., Saleh, M. N., Harris, M., Renschler, M. F., & Renschler, M. (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	9,101,543*PED	⤷ 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
European Patent Office	1853250	⤷ Start Trial	C300673	Netherlands	⤷ Start Trial
European Patent Office	1853250	⤷ Start Trial	CA 2014 00034	Denmark	⤷ Start Trial
European Patent Office	1853250	⤷ Start Trial	PA2014022	Lithuania	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,101,543

Which drugs does patent 9,101,543 protect, and when does it expire?

Summary for Patent: 9,101,543