Details for Patent: 10,947,197

Which drugs does patent 10,947,197 protect, and when does it expire?

Patent 10,947,197 protects PYLARIFY and PYLARIFY TRUVU and is included in two NDAs.

This patent has twenty-nine patent family members in seventeen countries.

Summary for Patent: 10,947,197

Title:	Synthesis of the radiolabeled prostate-specific membrane antigen (PSMA) inhibitor [18F]DCFPyL
Abstract:	Methods, and related compositions, for the improved synthesis of [18F]DCFPyL are disclosed. Also provided are methods, and related compositions, for the use of [18F]DCFPyL so produced.
Inventor(s):	Hayden T. Ravert, Daniel P. Holt, Ying Chen, Ronnie C. Mease, Hong Fan, Martin G. Pomper, Robert F. Dannals
Assignee:	Johns Hopkins University
Application Number:	US16/308,128
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Device;

US Patent 10,947,197: DCFPyL Synthesis, Composition and PSMA Imaging Patent Landscape

US Patent 10,947,197 protects a manufacturing process for producing [18F]DCFPyL, the active radiotracer in piflufolastat F 18, marketed as Pylarify. Its strongest protection is directed to the combination of radiofluorination, phosphoric-acid deprotection, temperature control, purification, and a minimum specific activity of 40 Ci/μmol. Dependent claims extend protection to automated synthesis modules, cartridge-based fluoride handling, precursor preparation, C18 purification, and compositions with specific activity thresholds up to at least 150 Ci/μmol.[1]

The patent is principally a process and product-by-process patent. It is not a broad patent on the DCFPyL molecular scaffold or on PSMA imaging generally. The commercial exposure is significant because an alternative commercial manufacturing route could avoid some process limitations, but a route that reproduces the claimed reaction sequence and product specifications may create infringement risk.

What does US Patent 10,947,197 protect?

The patent has four principal claim groups:

Claim group	Claims	Protected subject matter	Commercial relevance
Synthesis process	1-7, 13-29	Radiofluorination of protected DCFPyL precursor, phosphoric-acid deprotection, purification and specific activity	Primary manufacturing protection
Composition	8, 30-33	[18F]DCFPyL composition with specific activity of at least 40, 60, 100, 120 or 150 Ci/μmol	Product-level risk
Kit	9	Kit containing the claimed composition	Distribution and diagnostic-use risk
Imaging, administration and treatment	10-12	Imaging, administration and treatment methods using the claimed composition	Downstream-use protection

Claim 1 is the central independent process claim. It requires all of the following:

1. A DCFPyL precursor containing ester protecting groups.
2. Radiofluorination to form a protected, radiofluorinated intermediate.
3. Deprotection with phosphoric acid.
4. A deprotection temperature between 30°C and 55°C.
5. Purification from the reaction mixture.
6. Final [18F]DCFPyL with specific activity of at least 40 Ci/μmol.

A process that omits any one of these express limitations may avoid literal infringement of claim 1, although other claims or the doctrine of equivalents could remain relevant.

How narrow is the core process claim?

Claim 1 is narrower than a generic claim to making [18F]DCFPyL. It requires both a chemical sequence and a product-quality threshold. The most material limitations are:

• Phosphoric acid must be used for ester deprotection.
• The deprotection must occur at 30°C to 55°C.
• The product must reach at least 40 Ci/μmol specific activity.
• Purification must follow deprotection.
• The starting precursor must contain ester protecting groups.

A synthesis using hydrochloric acid, sulfuric acid, a solid acid, base-mediated hydrolysis, or another deprotection reagent would not literally satisfy the phosphoric-acid limitation. A process performed outside the claimed temperature range would also present a noninfringement position, subject to claim construction and equivalents analysis.

The specific-activity limitation creates a technical and evidentiary issue. It is a claim limitation, not merely a quality objective. An accused manufacturer would likely need batch records, analytical results, calibration data and validated specific-activity calculations to establish whether the threshold was met.

What are the most important dependent claims?

Claims 2 through 6 protect process configuration and automation.

One-reactor synthesis

Claim 2 requires radiofluorination and deprotection in one reactor. A single-vessel process using the claimed chemistry is more exposed than a process that transfers the intermediate to a separate vessel.

Automated radiofluorination module

Claim 3 covers automation using a radiofluorination module with:

• A heating block
• Two syringe pumps
• A multi-port cap
• Valved reagent addition vials

Claim 4 adds a thermal heating cavity. Claim 5 extends the concept to an automated radiochemistry synthesizer. Claim 6 requires that components of the module or synthesizer be free of fluorine.

The automation claims may be difficult to apply against a commercial synthesizer unless the accused system has the specified structural components. They are stronger against a purpose-built or substantially copied cassette and module design than against a general-purpose radiochemistry platform.

Precursor manufacturing

Claims 7, 13, 14 and 15 address preparation of the DCFPyL precursor. Claims 13 and 14 identify coupling between:

• N,N,N-trimethyl-5-((2,3,5,6-tetrafluorophenoxy)carbonyl)pyridin-2-aminium trifluoromethanesulfonate; and
• A protected aminopentyl urea pentanedioate intermediate.

The supplied claim text does not reproduce the chemical scheme referenced in claims 7 and 15. Those claims therefore cannot be evaluated completely from the text alone. Their likely function is to capture a particular precursor route and radiofluorination sequence disclosed in the patent.

What radiofluorination steps are protected?

Claims 16 through 24 define a specific [18F]fluoride preparation sequence:

1. Trap [18F]fluoride on a cartridge.
2. Elute with a tetrabutylammonium base salt.
3. Dry the eluate.
4. Add compound (3) to the dried fluoride.
5. Heat the combined solution.

The claims narrow the process through specific operating parameters:

Limitation	Claimed range or requirement
Cartridge	Anion-exchange chromatographic cartridge
Cartridge pretreatment	Washed with water
Drying temperature	80°C to 150°C
Drying time	50 to 300 seconds
Drying atmosphere	Nitrogen flow
Additional drying solvent	Acetonitrile may be added
Radiofluorination temperature	30°C to 70°C
Radiofluorination time	2 to 10 minutes

These claims are directed at reproducibility and automation. They are relevant to manufacturers using conventional cyclotron-produced [18F]fluoride, anion-exchange trapping and tetrabutylammonium elution.

Claims 16 through 24 are narrower than claim 1. A manufacturer may avoid them by using a different fluoride-trapping medium, a different eluent, another drying protocol or a different radiofluorination temperature. That does not automatically avoid claim 1 if the overall process still uses phosphoric-acid deprotection and satisfies the remaining limitations.

What compositions are protected by US 10,947,197?

Claim 8 covers a composition comprising [18F]DCFPyL with a specific activity of at least 40 Ci/μmol. Claims 30 through 33 create escalating thresholds:

Claim	Specific-activity threshold
8	At least 40 Ci/μmol
30	At least 60 Ci/μmol
31	At least 100 Ci/μmol
32	At least 120 Ci/μmol
33	At least 150 Ci/μmol

The composition claims are potentially broader than the process claims because they do not expressly require the use of phosphoric acid, a particular precursor, or a particular synthesizer. A commercial product can therefore face composition-claim exposure even if the manufacturer uses a different synthesis route.

The scope depends heavily on claim construction. The phrase “comprising [18F]DCFPyL” generally permits additional components, such as residual solvents, buffers, excipients, stabilizers or radiochemical impurities. The claim does not appear limited on its face to a particular formulation, pH, sterile container, dose volume or excipient system.

What formulations are protected?

The supplied claims do not recite a defined formulation containing specific excipients, buffers, tonicity agents or preservatives. The patent therefore does not appear to provide a conventional formulation patent in the narrow sense.

The composition claims may nevertheless reach a formulated radiopharmaceutical if the formulation contains [18F]DCFPyL at the required specific activity. Product characterization would be important because the claim threshold is measured against the composition as claimed, while specific activity can vary with:

• Radioactivity at the time of measurement
• Total DCFPyL mass
• Residual nonradioactive precursor
• Decay during transport and administration
• Analytical method and calibration

A lower-specific-activity batch may avoid claims 30 through 33 while remaining within claim 8 if it remains at or above 40 Ci/μmol.

What is the FDA and Orange Book status of piflufolastat F 18?

The FDA approved Pylarify, piflufolastat F 18 injection, under NDA 214793 on May 27, 2021. The product is indicated for positron emission tomography imaging of prostate-specific membrane antigen-positive lesions in specified prostate-cancer settings.[2]

Regulatory item	Status
Product	Pylarify
Active radiopharmaceutical	Piflufolastat F 18, also called [18F]DCFPyL
Sponsor at approval	Lantheus Holdings, Inc.
FDA pathway	New drug application
NDA	214793
Approval date	May 27, 2021
Primary use	PSMA PET imaging in prostate cancer

The FDA-approved label identifies piflufolastat F 18 as a diagnostic radiopharmaceutical. Its short physical half-life, approximately 110 minutes, requires decentralized or regional production and rapid distribution.[2]

Orange Book relevance should be separated from patent validity. A patent listed for the NDA can create a Paragraph IV certification issue for an abbreviated new drug application, but listing does not establish that the patent is valid, infringed or enforceable. Manufacturing-process claims may also face questions about whether they qualify for listing under the Hatch-Waxman patent-listing framework.[3,4]

When does US Patent 10,947,197 lose exclusivity?

The patent issued on March 16, 2021. Its nominal term is generally calculated from the relevant nonprovisional or PCT filing date, not from the grant date. Based on the patent family’s reported 2017 priority context and later international filing structure, the ordinary expiration is expected to fall in the late 2030s, subject to the actual patent-term calculation, patent-term adjustment and any applicable extension.[1]

Event	Date or timing
Earliest reported priority context	2017
Grant	March 16, 2021
Nominal statutory term	20 years from applicable nonprovisional/PCT filing
Expected ordinary expiry	Late 2030s
Patent-term adjustment	Must be included in the USPTO patent record
Patent-term extension	No extension is established by the supplied record

The grant date does not mean exclusivity ends in 2041. Patent term normally runs from the earliest effective nonprovisional filing in the relevant family, subject to adjustment.

FDA regulatory exclusivity is separate. Pylarify’s approval date and any applicable new-chemical-entity, orphan, pediatric or other exclusivity period do not automatically match the patent term. The short half-life of [18F]DCFPyL also limits the practical value of ordinary commercial stockpiling, making manufacturing access and regional production central competitive issues.

Are there Paragraph IV challenges or patent litigation?

The supplied record identifies no Paragraph IV certification, district-court infringement action, settlement agreement or post-grant proceeding involving US 10,947,197. A complete live-status conclusion requires the current USPTO Patent Center record, FDA Orange Book listing data and federal court docket review.

The principal litigation scenarios would be:

1. An ANDA applicant certifies Paragraph IV against a listed product or method patent.
2. A competing radiopharmaceutical manufacturer uses a materially similar DCFPyL synthesis route.
3. A contract manufacturing organization produces Pylarify or a competing [18F]DCFPyL product.
4. A sponsor asserts composition claims 8 or 30-33 against a product made by a different process.
5. A manufacturer challenges validity based on anticipation, obviousness, written description, enablement or indefiniteness.

The strongest potential validity pressure points are the breadth of the composition claims, the measurement of specific activity, and the relationship between the claimed synthesis parameters and prior DCFPyL radiochemistry methods. The strongest infringement issues are proof of the precise acid, temperature, reactor configuration and specific-activity result.

How strong is the patent estate for DCFPyL?

US 10,947,197 appears strongest as a manufacturing-control patent rather than as a foundational molecule patent.

Estate dimension	Assessment
Core DCFPyL molecule	Not the principal subject of the supplied claims
PSMA imaging concept	Not broadly claimed
Manufacturing process	Strongest area
Automated production	Meaningful protection through dependent claims
Product composition	Potentially broad, subject to specific-activity proof
Formulation	Limited express protection
Treatment method	Broad wording but potentially vulnerable to utility and claim-construction challenges
Supply-chain control	Important because of short isotope half-life
Generic substitution	More difficult than ordinary small-molecule substitution because production must be local or regional

The estate’s commercial value is linked to manufacturing know-how. A competitor may avoid a process claim through a redesigned route, but must still solve precursor supply, cyclotron access, radiochemical yield, quality control, sterility, release testing and delivery timing.

How does Pylarify compare with competing PSMA radiopharmaceuticals?

Product	Active agent	Modality	Patent and competition profile
Pylarify	Piflufolastat F 18 / [18F]DCFPyL	PSMA PET	Manufacturing and product-specific exposure under US 10,947,197
Illuccix	Ga-68 gozetotide / PSMA-11	PSMA PET	Different isotope, chelator and manufacturing platform
Locametz	Ga-68 gozetotide	PSMA PET	Competes for PSMA PET use but does not use [18F]DCFPyL chemistry
Axumin	Fluciclovine F 18	Amino-acid PET	Prostate-cancer imaging competitor, not a PSMA agent

The main commercial substitutes are gallium-68 PSMA products, particularly Ga-68 gozetotide. They avoid the specific DCFPyL chemistry in US 10,947,197 but compete for imaging capacity, physician adoption, reimbursement and patient scheduling.

What generic-entry risks exist?

A conventional generic launch is less straightforward than for an oral small-molecule drug. Potential entrants face four separate barriers:

Regulatory barrier

An ANDA or other abbreviated pathway must establish the required relationship to the reference product and address product-specific radiopharmaceutical requirements. A competing diagnostic may instead pursue a full NDA or another regulatory route.

Patent barrier

The entrant must evaluate:

• US 10,947,197 composition claims
• Any separate DCFPyL molecule or precursor patents
• Method-of-use patents
• Orange Book-listed patents
• Patent-term adjustment
• Licensing or settlement restrictions

Manufacturing barrier

The entrant needs validated access to:

• Cyclotron-produced [18F]fluoride
• Anion-exchange cartridges or an alternative fluoride-handling system
• Protected DCFPyL precursor
• Automated radiochemistry equipment
• Sterile filtration and release testing
• Regional distribution infrastructure

Commercial barrier

Because [18F] decays rapidly, the entrant needs a network of production sites near imaging centers. A theoretical noninfringing process has limited value unless it can meet dose availability, release timing and reimbursement requirements.

What licensing deals affect the patent landscape?

Progenics developed the DCFPyL program and Lantheus commercialized Pylarify after acquiring rights associated with the program. The FDA-approved product is marketed by Lantheus.[2] Commercial rights, patent ownership, manufacturing rights and product sponsorship should be distinguished. A license or acquisition may transfer commercial control without transferring every patent claim or every right to practice a manufacturing method.

No settlement agreement or patent license specific to US 10,947,197 is identified in the supplied record.

Key Takeaways

• US 10,947,197 primarily protects a defined process for making [18F]DCFPyL.
• Claim 1 requires phosphoric-acid deprotection at 30°C to 55°C and a final specific activity of at least 40 Ci/μmol.
• Claim 8 creates separate composition exposure at the 40 Ci/μmol threshold.
• Claims 30-33 raise the composition thresholds to 60, 100, 120 and 150 Ci/μmol.
• Automation, anion-exchange fluoride trapping, tetrabutylammonium elution, nitrogen drying and C18 purification are separately addressed.
• The patent does not appear, from the supplied claims, to be a broad patent on the DCFPyL scaffold or PSMA imaging.
• The nominal patent term is expected to extend into the late 2030s, subject to the official term calculation.
• Pylarify received FDA approval on May 27, 2021, under NDA 214793.
• A process redesign may avoid selected manufacturing claims, but composition claims create a separate product-level risk.
• The short half-life of fluorine-18 makes manufacturing location, automation and distribution as important as patent clearance.

FAQs

Does US 10,947,197 cover all methods of making [18F]DCFPyL?

No. The independent process claim requires protected ester groups, radiofluorination, phosphoric-acid deprotection at 30°C to 55°C, purification and specific activity of at least 40 Ci/μmol.

Can a manufacturer avoid the patent by using hydrochloric acid instead of phosphoric acid?

That approach may avoid the literal phosphoric-acid limitation in claim 1, but infringement must be assessed against the full claim set, equivalents and the composition claims.

Does the patent cover gallium-68 PSMA-11 products?

No. The claims supplied are directed to [18F]DCFPyL and its production, composition and use. Gallium-68 gozetotide products use a different radiometal and chemical platform.

Is a specific activity of 150 Ci/μmol required for Pylarify?

The patent contains a dependent composition claim at that threshold. The claim does not establish that every FDA-approved Pylarify dose must have a specific activity of at least 150 Ci/μmol.

Can a contract manufacturer produce [18F]DCFPyL without a license?

Not necessarily. A contract manufacturer using the claimed process or supplying a composition within the composition claims could create direct or contributory infringement exposure, depending on authorization, ownership and the applicable patent rights.

References

1. United States Patent No. 10,947,197. (2021). Methods for the synthesis of [18F]DCFPyL. United States Patent and Trademark Office.
2. U.S. Food and Drug Administration. (2021). Pylarify (piflufolastat F 18) injection prescribing information.
3. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. 35 U.S.C. § 271(e)(2) (2023). Action for infringement based on certain activities related to regulated products.

Drugs Protected by US Patent 10,947,197

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Progenics Pharms Inc	PYLARIFY	piflufolastat f-18	SOLUTION;INTRAVENOUS	214793-001	May 26, 2021		RX	Yes	Yes			Y	Y		METHOD OF POSITRON EMISSION TOMOGRAPHY (PET) IN MEN WITH PROSTATE CANCER
Aphelion	PYLARIFY TRUVU	piflufolastat f-18	SOLUTION;INTRAVENOUS	220089-001	Mar 6, 2026		RX	Yes	Yes			Y	Y		POSITRON EMISSION TOMOGRAPHY (PET) OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITIVE LESIONS IN MEN WITH PROSTATE CANCER

Foreign Priority and PCT Information for Patent: 10,947,197

PCT Information
PCT Filed	June 09, 2017	PCT Application Number:	PCT/US2017/036681
PCT Publication Date:	December 14, 2017	PCT Publication Number:	WO2017/214470

International Family Members for US Patent 10,947,197

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3026889
Canada	3240630
China	109563038
China	122187723
China	122187724
Denmark	3481804
European Patent Office	3481804