Scope and claims of US Patent 11,027,031 (Ga-68 radiolabeling with acetate buffer, inhibitors and self-shielded generator devices)
US Patent 11,027,031 claims a tightly specified US method-of-manufacture workflow for radiolabeling chelate-functionalized targeting agents with gallium-68 eluted from a gallium-68 generator inside a self-shielded device. The core claim 1 requires (i) an acetate buffer added to balance the eluate pH to 3 to 5, (ii) co-formulated “metal inhibitor” selected from DOTA, glucose, fructose, beta-cyclodextrin, D-mannose, tetra-tBu-DTPA, and (iii) a chelator selected from NOTA, NODAGA, HBED, and DFO, with a defined generator eluate transfer-and-incubation sequence. Dependent claims add minimum incubation time, a needleless transfer architecture with vials/vial adapter/extension line and needleless syringe, detailed valve/luer-lock configurations, self-shielded device geometry (rotatable container unit), and a specific targeting agent (PSMA-11) plus an in vivo PET imaging method.
From a landscape perspective, the claim set is not “broad radiolabeling chemistry.” It is a platform around (a) particular chelators and specific metal inhibitors, (b) pH window 3-5 via acetate buffering, and (c) radiation-protective, vial-to-syringe needleless transfer hardware that likely maps to commercial self-shielded Ga-68 generator labeling kits. Design-around risk is therefore concentrated in methods that use the same inhibitor/chelator/pH combination and similar needleless shielded-transfer workflows. If the inhibitor/chelator choices or the pH targeting strategy differ, or if formulation is not acetate-buffer pH-adjusted to 3-5 before contact with Ga-68 eluate, the ability to avoid claim 1’s center of gravity improves. Hardware-based dependencies (valves, luer-lock, extension line) can be avoided by changing transfer mechanics even if the chemical radiolabeling logic stays similar.
What does US 11,027,031 claim cover: Ga-68 radiolabeling workflow, chemistry, and device architecture?
Claim 1: required elements and claim “center of gravity”
Claim 1 is a single comprehensive method claim with multiple “must-have” limitations. It can be decomposed into three technical layers.
Layer A: chemical formulation limitations (chelators, metal inhibitors, acetate buffer, pH 3-5)
- The method radiolabels a “chelate-functionalized targeting agent” with gallium-68 recovered from a Ga-68 generator.
- A second vial contains a lyophilized chelate-functionalized targeting agent plus a lyophilized “metal inhibitor.”
- Acetate buffer is added in a “suitable amount” so that, when the mixture is contacted with the Ga-68 generator eluate, the pH is in the range 3 to 5.
- The “metal inhibitor” is limited to the closed group:
- DOTA
- glucose
- fructose
- beta-cyclodextrin
- D-mannose
- tetra-tBu-DTPA
- The chelator in the chelate-functionalized targeting agent is limited to the closed group:
This is the core patentable “chemistry scope”: the combination of (i) only those chelators, (ii) only those inhibitors, and (iii) acetate-buffered pH balancing to 3-5 upon contact with Ga-68 eluate.
Layer B: generator eluate recovery and shielded transfer into vial 1
- Ga-68 generator eluate is recovered into a first vial located within a “self-shielded device.”
- The acetate-buffer/inhibitor/chelate mixture recovered from the second vial is then added to the recovered eluate in vial 1 within the shielding.
This positions the invention in “kit-like” manufacture where shielding is integrated into the labeling vessel.
Layer C: process outcome and timing
Claim 1 ends with allowing radiolabelling of the chelate-functionalized targeting agent with Ga-68.
No explicit endpoint (radiochemical purity, stability, or acceptance criteria) is required in claim 1 itself. Dependent claims add at least 1 minute incubation (claim 2).
Claim 2: minimum incubation time
Claim 2 adds: radiolabelling is performed for at least 1 minute. This is a straightforward duration limitation. In practice, many Ga-68 labeling workflows incubate for several minutes, so the “at least 1 minute” threshold is likely easily met by typical operations.
Claims 3, 4, 5, 6, 7, 8: needleless shielded architecture and “how” acetate buffer and mixtures are moved
These claims are where infringement risk shifts from chemistry to hardware.
Claim 3: vial adapter + extension line + needleless syringe
Claim 3 specifies:
- First vial within the self-shielded device is connected to a vial adapter.
- Vial adapter connects to an extension line.
- Extension line distal end connects to a needleless syringe outside the shielding device.
This is a typical “remote syringe access” concept.
Claim 4: acetate buffer in a third vial + needleless transfer device
Claim 4 adds:
- Acetate buffer amount is contained in a third vial.
- Buffer is added to vial 2 (lyophilized chelate-functionalized targeting agent + metal inhibitor) by interconnecting second and third vials via a needleless transfer device.
Claims 5-7: specific needleless transfer device mechanics
Claim 5: needleless transfer device comprises a valve and a luer-lock.
Claim 6 adds detailed valve/luer-lock configuration with third vial positioned above second vial and valve configured to enable fluid communication among different combinations, followed by mixing.
Claim 7 adds a more explicit valve and aspiration procedure:
- Valve configured to communicate with second vial and capped luer-lock but not third vial.
- Uncap luer-lock.
- Connect needleless syringe containing air volume at least 50% of vial 2 volume.
- Inject that air into vial 2 via the uncapped luer-lock.
- Turn the vials (third vial above second vial) and withdraw mixture via the uncapped luer-lock using the needleless syringe.
This claim set appears designed to capture a specific class of needleless transfer systems that use air displacement and controlled valve states.
Claim 8: injecting the mixture into vial 1 with needleless syringe
Claim 8 requires the mixture is injected into vial 1 within the self-shielded device using a needleless syringe.
Claims 9 and 10: self-shielded device container geometry and inversion
Claim 9 specifies a self-shielded device container unit with:
- a void space sized for the first vial
- a container unit rotatable around a horizontal axis
Claim 10 adds:
- inverting container unit
- withdrawing the Ga-68-labeled chelate-functionalized targeting agent from first vial
This suggests an ergonomic workflow that depends on controlled inversion within shielding to recover labeling mixture.
Claim 11 and claim 12: PSMA-11 specificity and in vivo PET imaging
Claim 11 fixes the targeting agent as PSMA-11.
Claim 12 adds an in vivo PET method:
- produce Ga-68 radiolabelled PSMA-11 using the method of claim 11
- administer to subject
- detect via PET
This is an application claim that ties method-of-manufacture to in vivo imaging.
How narrow is the claim scope for chelators and metal inhibitors in US 11,027,031?
Chelator list is closed: NOTA, NODAGA, HBED, DFO
Because claim 1 uses “selected from the group consisting of,” only those four chelators fall within claim scope. If a competitor uses other PSMA chelators (including certain DOTA-based PSMA constructs, NOTA derivatives beyond the listed chelator identity, or chelators not captured by those names), claim 1’s chelator limitation may not read.
Metal inhibitor list is also closed
Claim 1’s “metal inhibitor is selected from” the enumerated set. That narrows infringement risk. If a process uses a different “metal scavenger” or stabilizer not named (or uses no inhibitor), claim 1 is harder to hit.
Acetate buffer pH 3-5 is a key limiting condition
Claim 1 requires acetate buffer amount balancing the eluate contact pH to a numeric range: 3 to 5. If an alternative buffer system is used (e.g., citrate, phosphate, HEPES, or carbonates) or if pH adjustment targets outside 3-5, claim 1 can be avoided.
Practical read
Most Ga-68 radiolabeling kits operate at mildly acidic pH. Claim 1 targets that but also locks in acetate buffer specifically and locks the window to 3-5 upon contact.
What patents protect Ga-68 radiolabeled PSMA-11 in the US: where does US 11,027,031 fit?
US 11,027,031 is a US patent on method and device workflow, not a new PSMA-11 entity patent in isolation. It likely sits at the intersection of:
- radiopharmaceutical formulation/kit patents (lyophilized chelator-targeting agent plus metal inhibitor; buffer addition)
- radiolabeling process patents (pH window, co-formulated scavengers/inhibitors)
- Ga-68 generator kit hardware patents (self-shielded device, needleless syringe/valve/luer-lock transfer)
In typical Ga-68 PSMA intellectual property ecosystems, separate patent families often cover:
- PSMA-11 synthesis and chelation chemistry,
- radiolabeling reaction conditions (buffer type, pH, incubation time),
- “stabilizer/scavenger” use (metal inhibitors),
- kit format including lyophilization and vial architecture,
- shielding/needleless transfer systems for regulator/compliance constraints.
Because claim 1 is constrained to specific chelators, inhibitors, and acetate buffering and also constrained to a self-shielded needleless workflow, other patents in the landscape may be broader in chemistry but not in device mechanics, or broader in device but narrower in chemical components.
When does US 11,027,031 expire and when does exclusivity end for Ga-68 PSMA-11 labeling in the US?
A precise exclusivity timeline requires the patent’s filing date, priority data, and whether any PTA or adjustment applies, plus any FDA market exclusivity and patent term adjustments. This response contains the claims only. Without the bibliographic information (application number, priority date, filing date, PTA/adjustment), a complete and accurate expiration computation cannot be produced.
What is the Orange Book status of US 11,027,031?
Orange Book status is tied to an approved drug product listing (NDC) and patents listed for that product. US 11,027,031 is a method-of-radiolabeling and imaging method patent that may or may not be listed for a specific FDA-approved radiopharmaceutical product. Without the FDA product and Orange Book listing mapping, a complete and accurate Orange Book status assessment cannot be produced.
How strong is the patent estate for this Ga-68 radiolabeling method: infringement vectors and claim coverage
Infringement vectors
-
Chemical combination match
To read claim 1, an accused method must use:
- a chelate-functionalized targeting agent where the chelator is one of NOTA, NODAGA, HBED, DFO,
- co-use a metal inhibitor from the closed list,
- use acetate buffer and adjust the pH upon contact to 3-5,
- use a defined vial-transfer process involving a self-shielded generator eluate vial and a second vial holding lyophilized chelate-targeting agent and metal inhibitor.
-
Hardware mechanics match
If a competitor uses equivalent chemical steps but different transfer mechanics, dependent claims (3-8) may not read. But independent claim 1 already recites the “first vial located within a self-shielded device” and addition of recovered mixture into recovered eluate in that vial. So, device architecture is still required at the top level, not only in dependents.
-
PSMA-11 and in vivo imaging
Any radiolabeling that uses PSMA-11 as targeting agent could implicate claim 11 and the imaging method claim 12 if the in vivo sequence is followed by the method steps defined.
Where competitors can design around within the claim language
- Replace acetate buffer with another buffer system, or shift the contacting pH outside 3-5.
- Replace the metal inhibitor with a scavenger not in the enumerated list.
- Use a chelator outside NOTA/NODAGA/HBED/DFO list.
- Avoid the self-shielded device first-vial configuration, or change the process so that eluate is not recovered/handled within a “self-shielded device” as claimed.
What generic entry risks exist for Ga-68 PSMA-11 methods under US 11,027,031?
Radiopharmaceutical “generic” entry typically occurs via:
- alternative manufacturing processes by the same approved product pathway (not always a conventional ANDA),
- Section 351(k) for eligible biologics,
- or competitive sourcing by radiopharm manufacturers if the product is not protected by product-specific exclusivity.
However, this patent is not a composition claim; it is a method claim on radiolabeling process with specific formulation and device steps. The generic entry risk for a process competitor is mostly under:
- process infringement for manufacturing steps,
- use/administration infringement depending on claim 12 coverage and who performs the in vivo steps.
Which companies are likely challenging US 11,027,031 and what Paragraph IV or PGR signals matter?
This requires known litigation or PTAB record for the specific patent number. No litigation and no ownership/assignee details are provided. Without that, a complete and accurate identification of challengers, PGR petitions, or Paragraph IV structures cannot be produced.
What formulations and dosage forms are covered: lyophilized chelate-functionalized targeting agent plus lyophilized inhibitor
US 11,027,031 is explicitly centered on lyophilized inputs:
- second vial contains “lyophilized chelate-functionalized targeting agent and a lyophilized metal inhibitor”
- acetate buffer is added as a solution step after reconstitution/mixing in vial 2.
The claim also contemplates a mixing and recovery step (with valve/luer-lock and air displacement) to transfer a mixture into the generator eluate in shielded vial 1.
No final dosage formulation is claimed beyond the radiolabeled product in vial 1 and the intended imaging use.
Does US 11,027,031 cover a PSMA-11 Ga-68 kit: how the claims map to practical labeling kits
A typical Ga-68 PSMA-11 workflow that matches these claims would look like:
- recover Ga-68 generator eluate into a vial inside a self-shielded device,
- reconstitute a lyophilized PSMA-11 chelate with a co-lyophilized inhibitor using acetate buffer to achieve pH 3-5 on contact with eluate,
- add the reconstituted mixture to the shielded vial containing eluate,
- incubate at least 1 minute,
- withdraw labeled PSMA-11 from the shielded vial (with possible inversion/rotation steps).
Claims 3-8 indicate this is done with needleless syringes, adapters, extension lines, valves, and luer-locks.
Key Takeaways
- US 11,027,031 claims a Ga-68 radiolabeling method with a tight chemical core: closed lists of chelators (NOTA/NODAGA/HBED/DFO), closed list of metal inhibitors (DOTA/glucose/fructose/beta-cyclodextrin/D-mannose/tetra-tBu-DTPA), and acetate-buffer pH adjustment to 3-5 upon contact with Ga-68 generator eluate.
- The patent scope also requires operational device architecture: a first vial in a self-shielded device plus needleless transfer mechanics (in dependents) using vial adapters, extension lines, valve/luer-lock assemblies, and optionally inversion/rotation of the shielded container unit.
- PSMA-11 specificity appears in claim 11 and the imaging method in claim 12, linking manufacturing steps to in vivo PET detection.
- Design-around focus should be on (1) buffer identity and pH window, (2) selecting inhibitors and chelators outside the enumerated groups, and (3) changing shielding/needleless transfer workflow enough to avoid required “self-shielded” and transfer-architecture elements.
FAQs
-
Can a labeling process avoid US 11,027,031 by using a different buffer than acetate?
Yes if the method does not satisfy the acetate-buffer and pH 3-5 contacting limitation of claim 1.
-
Does using a listed metal inhibitor but a chelator outside NOTA/NODAGA/HBED/DFO avoid infringement?
It avoids the claim 1 “chelator selected from the group consisting of” limitation if the chelator identity is outside the listed set.
-
Is the 1-minute incubation requirement a strict minimum that affects infringement risk?
Yes for claim 2, but claim 1 does not require a specific minimum time beyond allowing radiolabelling.
-
If a manufacturer uses a self-shielded device but uses a different transfer mechanism than valve/luer-lock, does that matter?
Yes primarily for dependent claims 5-7, but claim 1 still requires a first vial within a self-shielded device and the defined addition sequence.
-
Does claim 12 create liability for clinicians administering Ga-68 PSMA-11?
It can, because claim 12 is an in vivo imaging method requiring producing Ga-68 radiolabeled PSMA-11 using the claimed method and then administering and detecting by PET.
References
- United States Patent 11,027,031 (claims provided in prompt).
