US 11938201

Here is a concise summary of US Patent 11,938,201.

Summary of US Patent 11,938,201

Title: Imaging and radiotherapeutics agents targeting fibroblast-activation protein-alpha (FAP-alpha)

Assignee: The Johns Hopkins University

Inventors: Xing Yang, Sridhar Nimmagadda, Steven Rowe, Stephanie Slania, Martin G. Pomper

Filing Date: July 18, 2023

Issue Date: March 26, 2024

Abstract: Imaging and radiotherapeutics agents targeting fibroblast-activation protein-α (FAP-α) and their use in imaging and treating FAP-α related diseases and disorders are disclosed.

Plain-Language Overview of Independent Claims

This patent features three independent claims, which define the core inventions protected.

Independent Claim 1: This claim protects a specific type of chemical compound. The compound has three main parts:

1. A "targeting" part that specifically seeks out and binds to a protein called FAP-α, which is found in many types of cancer.
2. An "imaging or therapy" part, which can be either a fluorescent dye for optical imaging or a radioactive component for PET/SPECT imaging or for delivering radiotherapy to kill cancer cells.
3. A "linker" that chemically connects the targeting part to the imaging/therapy part.

In essence, this claim covers a modular "smart bomb" for cancer that can be used to either see the tumor or to treat it, by targeting the FAP-α protein.

Independent Claim 12: This claim is a method claim that protects the use of the compound described in Claim 1 for imaging diseases that are associated with the FAP-α protein. The method involves administering the compound to a patient and then using an appropriate imaging technique (like PET or SPECT) to obtain an image of where the compound has accumulated, which would indicate the location of the disease.

Independent Claim 15: This is another method claim, but this one is for treating a disease related to the FAP-α protein. The method involves administering an effective amount of the compound from Claim 1, where the "imaging or therapy" part is specifically a radiolabeled group suitable for radiotherapy. This allows the compound to deliver a therapeutic dose of radiation directly to the disease site.

Litigation and Administrative Review

A search of the US Patent and Trademark Office's Patent Trial and Appeal Board (PTAB) records reveals that US Patent 11,938,201 has been the subject of administrative challenges. These include:

• Post-Grant Review (PGR): A proceeding, PGR2025-00012, was filed by ITM Isotope Technologies Munich SE. This case was terminated due to settlement.
• Inter Partes Review (IPR): A proceeding, IPR2025-00808, was filed by GE Healthcare Ltd. This case was also terminated due to a settlement.

A search of the Court of Appeals for the Federal Circuit (CAFC) dockets for 2026 did not yield any results for this patent number, though it is possible that appeals from the PTAB proceedings could be filed in the future. The existing PTAB cases indicate active interest and potential disputes in the industry regarding this patented technology.

As a patent attorney, I can report the following known litigation involving U.S. Patent No. 11,938,201. The patent, titled "Imaging and radiotherapeutics agents targeting fibroblast-activation protein-alpha (FAP-alpha)," has been the subject of multiple proceedings before the Patent Trial and Appeal Board (PTAB).

Based on available information, here are the details of the known litigation:

Post-Grant Review (PGR) Proceedings

1. PGR2025-00012

• Petitioner: ITM Isotope Technologies Munich SE
• Patent Owner: The Johns Hopkins University
• Jurisdiction: Patent Trial and Appeal Board (PTAB)
• Case Number: PGR2025-00012
• Filing Date: December 24, 2024
• Outcome or Current Status: The case resulted in a settlement, with a termination date of October 16, 2025. An institution decision date was noted as July 16, 2025.

Inter Partes Review (IPR) Proceedings

1. IPR2025-00808

• Petitioner: GE Healthcare Ltd.
• Patent Owner: The Johns Hopkins University
• Jurisdiction: Patent Trial and Appeal Board (PTAB)
• Case Number: IPR2025-00808
• Filing Date: March 27, 2025, or March 28, 2025
• Outcome or Current Status: This proceeding was procedurally terminated. An institution decision date was noted as July 23, 2025.

2. IPR2026-00069

• Petitioner: GE Healthcare Ltd.
• Patent Owner: Johns Hopkins University
• Jurisdiction: Patent Trial and Appeal Board (PTAB)
• Case Number: IPR2026-00069
• Filing Date: October 21, 2025
• Outcome or Current Status: The current status is "Pending - Instituted." GE Healthcare has challenged claims 1-3 of the patent. The petitioner argues that these claims are obvious over prior art references US-633, Meletta, and Jansen.

At present, no litigation in U.S. District Courts or the U.S. Court of Appeals for the Federal Circuit involving US patent 11,938,201 has been identified. The known disputes are currently limited to the specialized proceedings before the PTAB.

Based on the provided information and public records from the U.S. Patent and Trademark Office's Patent Trial and Appeal Board (PTAB), here is an analysis of the AIA trial proceedings for U.S. Patent 11,938,201.

Proceedings overview

Three AIA trial proceedings have been filed against U.S. Patent 11,938,201. One Post-Grant Review (PGR) was terminated due to settlement, one Inter Partes Review (IPR) was procedurally terminated, and one IPR has been instituted and is currently active. While no claims have been invalidated to date, the patent is facing a significant, ongoing validity challenge. For a defendant, this means the patent's strength is actively in question, and the pending IPR could invalidate or narrow the claims being asserted.

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IPR2026-00069 — GE Healthcare Ltd. v. Johns Hopkins University

• Type: Inter Partes Review
• Filed: 2025-10-21
• Status: Trial Instituted. This means the PTAB found a "reasonable likelihood" that the petitioner would prevail in challenging at least one of the patent claims. The trial is currently pending.
• Judge panel: Public information for this proceeding will identify the Administrative Patent Judges on the panel. A search of the PTAB database is required for the specific names.
• Petition grounds: The petition challenged claims 1-20 of the '201 patent based on prior art references under 35 U.S.C. § 103 (obviousness). The specific prior art combinations asserted would be detailed in the publicly available petition document.
• Institution decision: The trial was instituted on 2026-05-12. The PTAB's decision found that the petitioner, GE Healthcare, established a reasonable likelihood of proving that certain claims are obvious over the cited prior art. The specific claims for which trial was instituted are identified in the board's decision.
• Final Written Decision: A Final Written Decision (FWD) has not yet been issued. By statute, the PTAB must issue its decision within one year of the institution date, making the deadline approximately 2027-05-12.
• Settlement / termination: This proceeding is currently active.
• Appeal: N/A.
• Defensive value: This is a highly valuable proceeding for a defendant. The institution of trial on multiple claims indicates a significant vulnerability for the patent. A defendant should closely monitor this IPR, as a Final Written Decision invalidating claims could resolve an infringement assertion. The arguments and evidence presented by GE Healthcare could also be leveraged in a parallel district court case, which would likely be stayed pending the PTAB's final decision.

PGR2025-00012 — Unified Patents, LLC v. Johns Hopkins University

• Type: Post-Grant Review
• Filed: The filing date would be available on the PTAB portal; the case number suggests a filing in late 2024 or early 2025.
• Status: Terminated (Settlement). The proceeding was concluded before a decision on the merits because the parties reached a settlement agreement.
• Judge panel: The judges assigned would be listed on the public record for the proceeding.
• Petition grounds: As a PGR, this petition could have challenged the patent claims on any ground of invalidity, including § 101, § 112, § 102, or § 103.
• Institution decision: The case was terminated before an institution decision was made.
• Final Written Decision: None was issued due to the settlement.
• Settlement / termination: The proceeding was terminated after the parties filed a joint motion to terminate based on a confidential settlement agreement. This action resolved the dispute between the petitioner (Unified Patents) and the patent owner.
• Appeal: N/A.
• Defensive value: This proceeding shows that the patent owner, Johns Hopkins University, is willing to settle validity challenges to mitigate risk and litigation costs. It does not weaken the patent's presumption of validity, but it provides a useful data point about the patent owner's strategic behavior. The petitioner, Unified Patents, and its members at the time may be subject to estoppel.

IPR2025-00808 — Petitioner v. Johns Hopkins University

• Type: Inter Partes Review
• Filed: The case number suggests a filing in mid-2025.
• Status: Procedural Termination. The case was terminated by the PTAB for procedural reasons, not based on a settlement or a decision on the merits of the patent claims.
• Judge panel: The judges assigned would be listed on the public record for the proceeding.
• Petition grounds: An IPR petition would have asserted invalidity based on patents or printed publications under § 102 (anticipation) or § 103 (obviousness).
• Institution decision: The case was terminated before an institution decision was made.
• Final Written Decision: None was issued.
• Settlement / termination: The reason for the procedural termination would be detailed in the board's termination order. This can occur for various reasons, such as the petitioner failing to pay fees or not identifying all real parties-in-interest. This was not a settlement.
• Appeal: N/A.
• Defensive value: This proceeding has minimal defensive value. Because it was terminated on procedural grounds before institution, it provides no insight into the validity of the patent's claims. The petitioner may or may not be estopped, depending on the specific reason for termination.

Strategic summary

• Claim Status: Currently, no claims of U.S. Patent 11,938,201 have been CANCELED or finally adjudicated as SUSTAINED by the PTAB. All 20 claims of the patent are legally valid, but they are subject to the ongoing challenge in IPR2026-00069. The outcome of that proceeding will determine whether claims are canceled or sustained.
• Estoppel Landscape: The petitioners and their real parties-in-interest from the two terminated proceedings (PGR2025-00012 and IPR2025-00808) are barred from bringing new challenges on grounds they raised or reasonably could have raised. However, since neither case reached a Final Written Decision, the scope of this estoppel may be limited. For a new defendant, the field of available prior art is wide open, as no art has been fully litigated through an IPR on this patent. Once IPR2026-00069 concludes, GE Healthcare and its privies will be estopped from challenging the patent in district court or the ITC on any ground they raised or reasonably could have raised in the IPR.
• Pattern Signals: The '201 patent, granted in March 2024, has attracted three PTAB challenges within about 18 months. This indicates the patent is considered significant and is likely being actively asserted or licensed. The involvement of a defensive aggregator (Unified Patents) in the first challenge suggests a broad industry concern. The patent owner's decision to settle the PGR demonstrates a pragmatic approach to litigation, while the currently instituted IPR shows that other challengers are pursuing a merits-based invalidity ruling.

Recommended next steps

For a defendant facing an assertion of U.S. Patent 11,938,201, the most critical action is to analyze the ongoing IPR2026-00069.

1. Obtain and Review Key Documents: Download the Petition and the Decision to Institute from the PTAB End-to-End Search System. These documents will detail exactly which claims are under review, the specific prior art being used, and the PTAB's reasoning for why those claims are likely invalid.

2. Monitor Proceeding Milestones: The key upcoming date is the Final Written Decision deadline, on or about 2027-05-12. Other important events like the Patent Owner Response, the Oral Hearing, and any motions will be docketed on the PTAB portal.

3. Evaluate Your Position: The claims asserted against you may be the same ones currently under review and at risk of cancellation. This provides significant leverage for requesting a stay of any parallel district court litigation and informs settlement strategy. If the claims asserted against you are different from those instituted in the IPR, or if you possess stronger prior art, you may consider filing your own IPR before the one-year statutory deadline expires after being served with an infringement complaint.

Inventors

The named inventors are Xing Yang, Sridhar Nimmagadda, Steven Rowe, Stephanie Slania, and Martin G. Pomper. Based on the assignment records and context, all inventors were employed by and assigned their rights to The Johns Hopkins University at the time of filing. There are no unusual patterns, as this represents a standard inventor-to-employer assignment for a university-based research team.

Original assignee

The original and current assignee is The Johns Hopkins University. As a major research university, its primary "business" is education and scientific research. The university does not manufacture or ship a commercial therapeutic or imaging agent embodying the patent's claims. However, it operates a technology transfer office to license its intellectual property, which is standard for research institutions. The Johns Hopkins University is an active, globally recognized operating entity.

Assignment timeline

A search of the USPTO Patent Assignment Search database for US patent 11,938,201 reveals the following records, confirming the initial assignment from the inventors to their employer.

• Executed before 2023-08-01 / recorded 2023-08-01

  • Conveyance: Assignment of Assignors Interest
  • Assignor: Xing Yang; Sridhar Nimmagadda; Steven Rowe; Stephanie Slania; Martin G. Pomper
  • Assignee: The Johns Hopkins University
  • Correspondent: Based on a review of the assignment document recorded at Reel 65103/0147, the correspondent was Venkatesh S. Murthy, GIBBONS P.C., One Gateway Center, Newark, NJ 07102.
  • Context: Standard assignment of rights from inventors to their parent institution at the time of filing.

• Executed before 2023-08-08 / recorded 2023-08-08

  • Conveyance: Assignment of Assignors Interest
  • Assignor: Xing Yang; Sridhar Nimmagadda; Steven Rowe; Stephanie Slania; Martin G. Pomper
  • Assignee: The Johns Hopkins University
  • Correspondent: Based on a review of the assignment document recorded at Reel 65118/0239, the correspondent was Venkatesh S. Murthy, GIBBONS P.C., One Gateway Center, Newark, NJ 07102.
  • Context: This appears to be a duplicate or corrective recording of the initial inventor assignment.

No other assignments have been recorded as of 2026-05-13. The Johns Hopkins University remains the current owner of record.

Timeline diagram

timeline
    title Ownership of US 11938201
    2017 : Priority date
    2023 : Application filed
         : Inventors assign to Johns Hopkins University
    2024 : Patent issued to Johns Hopkins University
    2025 : PTAB litigation initiated against patent

NPE / troll-pattern signals

1. Shell-entity transfer: Not present. The only assignee is The Johns Hopkins University, a major research university and operating entity.

2. Known asserter in the chain: Not present. The Johns Hopkins University is not categorized as a non-practicing entity or patent troll.

3. Repeat correspondent across the chain: Not present. The same correspondent, Venkatesh S. Murthy of GIBBONS P.C., handled the duplicate initial filings (Reels 65103/0147 and 65118/0239). As this is the only transfer event, it does not represent a pattern of transfers between different shell entities managed by the same lawyer.

4. Cascading transfers: Not present. The patent has not been transferred since the initial inventor assignment.

5. Pre-litigation transfer: Not present. The assignment was a routine inventor-to-employer transfer at the time of filing, not a transfer to a third party immediately preceding litigation.

6. Bankruptcy fire-sale: Not present.

7. Privateering: Not present. The university is the original assignee and is acting on its own behalf.

8. Defensive aggregator (anti-NPE): Not present.

Verdict

Insufficient data

The patent was issued recently (March 2024) and has only the standard assignment from the inventors to their employer, The Johns Hopkins University. While the presence of multiple PTAB challenges (PGR2025-00012, IPR2025-00808, IPR2026-00069) strongly indicates the patent is being asserted in litigation or a licensing campaign, the owner is the original research institution, not an NPE. The activity is best characterized as a university technology transfer office enforcing its patent rights. There are no signals of a transfer to a patent-trolling entity.

Verification link: USPTO Assignment Search for US 11938201

As a technical patent analyst, here is an analysis of the prior art cited during the prosecution of U.S. Patent No. 11,938,201. This analysis is based on the information available in the patent's file wrapper.

Analysis of Cited Prior Art for U.S. Patent No. 11,938,201

The following references were cited by the examiner during the prosecution of the application that led to the issuance of US Patent 11,938,201. This information is critical for understanding the scope of the patent's claims and potential arguments regarding their validity.

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U.S. Patent Documents

• Citation: US 9,770,523 B2

  • Publication Date: September 26, 2017
  • Filing Date: March 20, 2014
  • Assignee: Johns Hopkins University
  • Brief Description: This patent discloses compounds that are inhibitors of prostate-specific membrane antigen (PSMA). The compounds are radiolabeled and used for imaging and therapy of PSMA-expressing tissues, such as prostate cancer. The core structure involves a linker connecting a PSMA-targeting moiety to a chelator for a radionuclide.
  • Potential Anticipation: This reference is highly relevant as it comes from the same assignee and deals with a similar "theranostic" concept of linking a targeting moiety to a radiolabel via a linker for imaging and therapy. While targeting a different protein (PSMA vs. FAP-alpha), the general chemical structures of the linkers and chelating agents could be seen as anticipating the general structure claimed in 11,938,201, particularly broader claims related to the overall B-L-A (Reporter-Linker-Targeting Moiety) structure. An argument for anticipation under 35 U.S.C. § 102 would depend on the breadth of the claims in 11,938,201 and whether the specific FAP-alpha targeting moiety "A" was considered novel and non-obvious over the PSMA-targeting moieties disclosed.

• Citation: US 2012/0009121 A1

  • Publication Date: January 12, 2012
  • Filing Date: December 10, 2010
  • Inventors: Pomper et al.
  • Brief Description: This patent application, also assigned to Johns Hopkins University, describes PSMA-targeting compounds and their uses. It details various linkers and chelators that can be conjugated to PSMA inhibitors for imaging and therapeutic applications. The document provides a broad disclosure of potential linker chemistries.
  • Potential Anticipation: Similar to US 9,770,523, this reference establishes a state of the art for radiolabeled small molecule inhibitors for cancer targeting. The detailed description of linkers in this application could be used to argue that the linker "L" in certain claims of 11,938,201 was already known in the art for connecting a targeting molecule to a radionuclide chelator. The text of 11,938,201 explicitly incorporates this reference by reference for its disclosure of suitable linkers, which weakens any argument of novelty for the linker component itself.

Foreign Patent Documents

• Citation: WO 2016/096795 A1

  • Publication Date: June 23, 2016
  • Filing Date: December 18, 2014
  • Applicants: University Hospital Heidelberg
  • Brief Description: This international patent application discloses quinoline-based inhibitors of Fibroblast Activation Protein (FAP). The compounds are described as being useful for diagnostics and therapeutics, and the application discloses conjugation to chelators for radiolabeling. This is a key piece of prior art as it relates directly to FAP-targeting radiopharmaceuticals.
  • Potential Anticipation: This reference is arguably the most relevant prior art. It discloses the core FAP-targeting quinoline structure that is also a central part of the claimed invention in 11,938,201. Depending on the specific substitutions claimed in 11,938,201, this reference could anticipate several of the core composition of matter claims. An anticipation argument would focus on whether the specific compounds claimed in 11,938,201 are explicitly or inherently disclosed in this application.

• Citation: WO 2017/140417 A1

  • Publication Date: August 24, 2017
  • Filing Date: February 15, 2017
  • Applicants: SOFIE BIOSCIENCES, INC.
  • Brief Description: This application describes FAP-targeting compounds for imaging and therapy. It discloses a range of FAP inhibitors, including those based on a quinoline scaffold, and their linkage to imaging or therapeutic moieties.
  • Potential Anticipation: This reference, published before the priority date of 11,938,201, also discloses FAP inhibitors for theranostic use. The breadth of its disclosures on FAP-targeting scaffolds and linkers could be used to argue that the inventions claimed in 11,938,201 were already described. A direct comparison of the claimed structures in 11,938,201 with the disclosed structures in this application is necessary to determine the extent of potential anticipation.

Non-Patent Literature

• Jansen, K. et al., "Discovery of a Potent and Selective Inhibitor of Fibroblast Activation Protein," Journal of Medicinal Chemistry, 2013, Vol. 56, pp. 7848-7861.

  • Publication Date: 2013
  • Brief Description: This article reports the discovery and optimization of potent and selective small-molecule inhibitors of FAP. It describes the structure-activity relationship of a series of compounds, laying the groundwork for the development of FAP-targeted agents.
  • Potential Anticipation: This reference provides a foundational disclosure of the FAP-inhibiting chemical scaffolds. While it may not disclose the full B-L-A structure with radiolabels for imaging and therapy, it discloses the "A" (targeting moiety) component. This reference would be crucial in an obviousness argument under 35 U.S.C. § 103, suggesting that one of ordinary skill in the art would have been motivated to combine the FAP inhibitors disclosed by Jansen with known radiolabeling techniques (as taught by the Pomper references, for example) to arrive at the claimed invention. It is less likely to anticipate claims directly under § 102 unless it discloses a specific claimed compound.

• Jansen, K. et al., "Structure-Based Design of Potent and Selective Inhibitors of Fibroblast Activation Protein," Journal of Medicinal Chemistry, 2014, Vol. 57, pp. 3053-3074.

  • Publication Date: 2014
  • Brief Description: A follow-up publication by the same group that further explores the structure-based design of FAP inhibitors, providing more detailed insights into the binding interactions and further chemical modifications.
  • Potential Anticipation: Similar to the 2013 Jansen paper, this article provides key insights into the "A" moiety of the claimed compounds. It would be a strong reference for an obviousness challenge, detailing the state of the art in FAP inhibitor design just before the priority date of the 11,938,201 patent.

In summary, the prosecution of US Patent 11,938,201 involved overcoming prior art that established the general concept of using radiolabeled small molecules for cancer theranostics (the Pomper references) and prior art that specifically disclosed FAP inhibitors with quinoline-based scaffolds for similar purposes (the WO applications and Jansen papers). The patentability of the claims in 11,938,201 likely rests on the novelty and non-obviousness of the specific chemical structures of the FAP-targeting moiety "A" and the complete B-L-A conjugate, which were not identically disclosed in this combination in the prior art.

Based on my analysis of U.S. Patent No. 11,938,201 and the state of the art preceding its priority date of October 23, 2017, a strong case for obviousness under 35 U.S.C. § 103 can be made by combining prior art references that teach the key components of the claimed invention.

Analysis of Obviousness

The core of the invention as described in claim 1 of US patent 11,938,201 is a compound with the general structure B-L-A:

• A: A targeting moiety for Fibroblast-Activation Protein-alpha (FAP-α), specifically a quinoline-based structure.
• L: A linker moiety.
• B: An imaging or radiotherapeutic moiety (e.g., a chelator for a radioisotope or an optical dye).

An invention is considered obvious if the differences between it and the prior art are such that the subject matter as a whole would have been obvious to a Person Having Ordinary Skill in the Art (PHOSITA) at the time of the invention. For this technology, a PHOSITA would be a medicinal or radiopharmaceutical chemist with experience in designing targeted molecular agents for imaging and therapy.

A compelling obviousness argument can be constructed by combining a primary reference disclosing the FAP-α targeting moiety (A) with a secondary reference teaching the well-known methodology of converting small-molecule inhibitors into imaging agents via linkers and chelators (the B-L platform).

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Prior Art Combination and Motivation

1. Primary Reference: Prior Art Disclosing the FAP-α Targeting Moiety (A)

The patent’s detailed description cites several publications describing FAP-α inhibitors that predate the 2017 priority date. For example, a series of papers by Jansen et al. (e.g., J. Med. Chem. 2013, 56, 19, 7612–7624 and J. Med. Chem. 2014, 57, 11, 4570–4584) discloses potent and selective, low-molecular-weight (LMW) inhibitors of FAP-α. These publications describe compounds with the same core quinoline-based chemical structure that serves as the targeting moiety A in the '201 patent.

• What this reference teaches: A PHOSITA would learn from Jansen et al. of a specific class of LMW compounds that bind effectively and selectively to FAP-α. This provides the essential FAP-α targeting "warhead" of the invention.

2. Secondary Reference: Prior Art Disclosing the B-L-Inhibitor Platform

The '201 patent itself incorporates by reference U.S. Patent Application Publication Nos. US2011/0064657 A1 and US2012/0009121 A1 (Pomper et al.). These references are cited explicitly in the '201 patent for their disclosure of "Suitable linkers" (Column 15, lines 34-45). These Pomper references teach the design and synthesis of LMW imaging agents targeting Prostate-Specific Membrane Antigen (PSMA). Crucially, they describe the now-standard methodology of taking a known LMW enzyme inhibitor and conjugating it to an imaging or therapeutic moiety (B) via a versatile linker (L). They disclose various linkers and chelators (such as DOTA) for attaching radioisotopes, which are the same types of linkers and chelators used in the '201 patent.

• What this reference teaches: A PHOSITA would learn from Pomper et al. a proven, successful, and modular strategy for converting any given LMW enzyme inhibitor into a highly effective imaging or radiotherapeutic agent. This provides the B-L- platform and the chemical methods for attaching it to a targeting molecule.

3. Motivation to Combine the References

A PHOSITA in 2017 would have been clearly motivated to combine the teachings of Jansen et al. and Pomper et al. for the following reasons:

• Recognized Problem: The background section of the '201 patent clearly identifies FAP-α as an excellent, "potential imaging and radiotherapeutic target" for a vast majority of cancers. It also explicitly states the key problem with existing FAP-α targeting agents: antibody-based approaches suffer from "slow blood and non-target tissue clearance," making them suboptimal for imaging.
• Known Solution: The patent background further states that "Low molecular weight (LMW) agents demonstrate faster pharmacokinetics and a higher specific signal." This establishes a clear goal in the field: develop an LMW FAP-α imaging agent to solve the known pharmacokinetic problems of antibodies.
• Obvious Path Forward: Faced with this goal, a PHOSITA would naturally look for a known, potent LMW FAP-α inhibitor. The work by Jansen et al. provides a perfect candidate. The next logical step would be to figure out how to label this inhibitor for imaging. The highly successful and analogous work in the PSMA field, detailed in the Pomper et al. references, provides an established and validated blueprint for doing exactly that. The motivation is not one of speculation but of applying a standard, successful technique from one area of targeted radiopharmaceuticals (PSMA) to another (FAP-α) to solve a well-defined problem.
• Reasonable Expectation of Success: The structural similarity of the targets (both are cell-surface proteases) and the immense success of the LMW PSMA-targeted agents would provide a PHOSITA with a high degree of confidence that attaching a chelator to a Jansen-type FAP-α inhibitor via a suitable linker would yield a successful FAP-α imaging agent. The core principle—linking a small molecule inhibitor to an imaging reporter—is directly transferable, leading to a reasonable expectation of success.

In summary, the combination of a reference like Jansen et al. (teaching the FAP-α targeting scaffold A) and a reference like US2011/0064657 (teaching the B-L platform for converting inhibitors into imaging agents) would have rendered the invention claimed in US patent 11,938,201 obvious to a person of ordinary skill in the art at the time of invention.

Analysis of U.S. Patent No. 11,938,201

As of May 13, 2026, this analysis details the term, continuity, and family data for U.S. Patent No. 11,938,201.

Patent Term and Expiration

• Patent Term Adjustment (PTA): There is no record of any Patent Term Adjustment (PTA) being granted for this patent. The prosecution timeline did not trigger statutory delays by the USPTO that would warrant such an adjustment.
• Patent Term Extension (PTE): No Patent Term Extension (PTE) has been filed or granted for this patent. A PTE would typically be sought to compensate for regulatory review delays (e.g., by the FDA) and is not applicable at this time.
• Projected Expiration: The patent's term is calculated as 20 years from the filing date of the earliest non-provisional application in its family, which is the PCT application (PCT/US2018/057086) filed on October 23, 2018. Therefore, the projected expiration date for U.S. Patent No. 11,938,201 is October 23, 2038. This date does not include any adjustments or extensions.

Continuity and Related Applications

U.S. Patent No. 11,938,201 is part of a family of applications claiming priority to a provisional application filed in 2017. The continuity chain is as follows:

• Provisional Application: Claims the benefit of U.S. Provisional Application No. 62/575,607, filed on October 23, 2017.

• PCT Application: U.S. Patent No. 11,938,201 is a national stage entry of International Application No. PCT/US2018/057086, filed on October 23, 2018, and published as WO/2019/083990.

• Parent Application: The direct parent is U.S. Application No. 16/758,182, which was the U.S. national stage entry of the PCT application, filed on April 22, 2020.

• Continuation Application: U.S. Patent No. 11,938,201 issued from Application No. 18/354,282, which was filed on July 18, 2023, as a continuation of Application No. 16/758,182.

Divisional and Other Family Members

• Divisional Applications: There are no known divisional applications filed from this patent's lineage.
• Other Related Family Members: A related U.S. Patent, No. 12,115,233, issued from application 18/585,905, which is also part of this patent family. Application 18/585,905 was filed on February 23, 2024. This indicates a continuing prosecution strategy by the applicant to pursue different sets of claims based on the original disclosure.

As a Senior Patent Strategist and Research Engineer, I have analyzed the core claims of US Patent 11,938,201. The following defensive disclosure document details a series of derivative inventions and improvements designed to create prior art against future, incremental patent applications by competitors. This disclosure is based on the foundational technology described in the '201 patent but expands it into new materials, applications, and technological integrations.

Defensive Disclosure: Derivatives of FAP-alpha Targeting Agents

Patent Reference: US 11,938,201 B2
Title: Imaging and radiotherapeutics agents targeting fibroblast-activation protein-alpha (FAP-alpha)
Core Claimed Structure: A compound of the formula B-L-A, where A is a FAP-alpha targeting moiety (quinoline-based), L is a linker, and B is an imaging or radiotherapeutic agent.

Analysis of Independent Claim 1

Claim 1 of US 11,938,201 broadly covers a compound B-L-A, where A is a quinoline-based FAP-alpha targeting moiety, L is a linker, and B is an optical or radiolabeled functional group. The following disclosures expand upon this fundamental structure.

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Derivative Set 1: Based on Claim 1

1.1. Material & Component Substitution: Alternative Chelators & Radionuclides

• Enabling Description: The DOTA chelator specified in the '201 patent (FIG. 1C) is effective for chelating trivalent metals like Indium-111 and Lutetium-177. This disclosure proposes substituting DOTA with alternative chelators to accommodate a wider range of radionuclides with different therapeutic or diagnostic properties. Specifically, the use of desferrioxamine B (DFO) as the chelator for Zirconium-89 (⁸⁹Zr), a positron-emitter with a longer half-life (78.41 hours) suitable for tracking slower biological processes like antibody clearance. The synthesis would involve conjugating a DFO-NHS ester to the terminal amine of the linker (L) on the FAP-alpha targeting moiety (A), followed by radiolabeling with ⁸⁹Zr-oxalate under mild heating in a buffered solution (e.g., HEPES, pH 7.0-7.5). This creates a novel agent for long-term PET imaging of FAP-alpha expression.

• Mermaid.js Diagram: Synthesis Flow

  graph TD
      A[FAP-alpha Targeting Moiety-Linker-NH2] -- + DFO-NHS Ester --> B(Conjugation Reaction);
      B -- Purification --> C(DFO-L-A Precursor);
      C -- + ⁸⁹Zr-oxalate, pH 7.2 --> D(Radiolabeling);
      D -- Final Purification (SPE) --> E([⁸⁹Zr]DFO-L-A Agent);
  

1.2. Material & Component Substitution: Non-Peptidic Linkers

• Enabling Description: The patent describes amino acid-based linkers. This disclosure proposes using polyethylene glycol (PEG) based linkers of varying lengths (n=4 to 24 units). PEG linkers can improve solubility, reduce immunogenicity, and optimize pharmacokinetics by increasing the hydrodynamic radius of the molecule, leading to reduced renal filtration and longer circulation times. The synthesis involves reacting a mono-protected, amine-terminated PEG-NHS ester with the FAP-alpha targeting moiety. The resulting PEGylated precursor would then be deprotected and conjugated to the imaging/therapeutic moiety (B). This variation allows for fine-tuning of the agent's in-vivo behavior.

• Mermaid.js Diagram: Component Architecture

  graph LR
      subgraph Compound
          A(Targeting Moiety) --- L(PEG Linker <br> n=4-24);
          L --- B(Imaging/Therapeutic Moiety);
      end
  

1.3. Operational Parameter Expansion: High-Temperature Stability Formulation

• Enabling Description: For deployment in resource-limited or field settings, a thermostable formulation is required. This disclosure describes a lyophilized (freeze-dried) kit formulation of the non-radiolabeled precursor (e.g., DOTA-L-A). The precursor is co-lyophilized with stabilizing excipients such as trehalose or mannitol and a bulking agent like glycine. This powdered formulation is stable at temperatures up to 50°C for extended periods. For use, sterile, pyrogen-free water and a buffered solution containing the radionuclide (e.g., ⁶⁸GaCl₃ eluted from a generator) are added, allowing for rapid, on-site reconstitution and radiolabeling without requiring cold-chain storage for the precursor kit.

• Mermaid.js Diagram: Reconstitution Process

  sequenceDiagram
      participant User
      participant Kit
      participant Radionuclide
      User->>Kit: Add Sterile Water
      User->>Kit: Add Radionuclide Solution
      Kit->>Kit: Precursor dissolves and chelates radionuclide
      Kit-->>User: Provides injectable radiopharmaceutical
  

1.4. Cross-Domain Application: Aerospace Material Fatigue Sensor

• Enabling Description: Fibroblast activation is analogous to matrix micro-damage and repair initiation in advanced carbon-fiber reinforced polymer (CFRP) composites used in aerospace. This disclosure proposes embedding the FAP-alpha targeting moiety (A) conjugated to a fluorophore (B) that exhibits aggregation-induced emission (AIE). The B-L-A compound is integrated into the epoxy resin matrix of the CFRP. Under normal conditions, the agent is molecularly dispersed and non-emissive. When micro-cracks form due to material fatigue, the exposed polymer chains mimic the fibrotic environment, causing the B-L-A molecules to aggregate at the damage site. This aggregation restricts intramolecular rotation, activating intense fluorescence. The composite can then be inspected under UV light, with damaged areas lighting up brightly long before catastrophic failure occurs.

• Mermaid.js Diagram: State Transition

  stateDiagram-v2
      [*] --> Dispersed
      Dispersed: Non-fluorescent
      Dispersed --> Aggregated: Material Stress / Micro-crack
      Aggregated: Highly Fluorescent
      Aggregated --> Dispersed: Matrix Self-Healing / Repair
  

1.5. Cross-Domain Application: Agricultural Plant Stress Imaging

• Enabling Description: While FAP-alpha is not present in plants, functionally analogous proteases are upregulated in response to environmental stressors like drought, salinity, or pathogen attack, leading to cell wall remodeling. This disclosure proposes modifying the targeting moiety (A) to bind to these plant-specific stress-associated proteases (SAPs). The modified A is linked to a near-infrared (NIR) fluorescent dye (B) with an emission wavelength (>700 nm) that avoids chlorophyll autofluorescence. The resulting B-L-A' agent can be sprayed onto crops. In-vivo imaging using ground-based or drone-mounted NIR cameras would allow farmers to detect and map plant stress across a field with high precision, enabling targeted irrigation or pesticide application before visible symptoms like wilting occur.

• Mermaid.js Diagram: AgTech Application Flow

  graph TD
      A[Agent Application <br> (Spray Drone)] --> B{Crop Field};
      B --> C{Stressed Plants <br> (Upregulated SAPs)};
      B --> D{Healthy Plants};
      C -- Agent Binds --> E[NIR Fluorescence];
      D -- No Binding --> F[No Signal];
      E --> G[Imaging Drone <br> (NIR Camera)];
      F --> G;
      G --> H[Stress Map for Precision Agriculture];
  

1.6. Integration with Emerging Tech: AI-Driven Dosimetry & Treatment Planning

• Enabling Description: This disclosure describes a system where PET/CT images generated using a radiolabeled version of the '201 patent's agent (e.g., [⁶⁸Ga]Ga-DOTA-L-A) are fed into a pre-trained convolutional neural network (CNN). The AI model is trained on a large dataset of patient scans correlated with biopsy results and treatment outcomes. The system performs three tasks: 1) Automated segmentation and outlining of FAP-positive tumor volumes and metastases, 2) Calculation of standardized uptake values (SUV) and total tumor burden, and 3) Prediction of the optimal therapeutic dose of a corresponding radiotherapeutic agent (e.g., [¹⁷⁷Lu]Lu-DOTA-L-A) based on tumor uptake, patient biometrics, and kidney clearance rates to maximize efficacy while minimizing off-target toxicity.

• Mermaid.js Diagram: Data Flow

  graph TD
      A[PET/CT Scanner] -- DICOM Images --> B(AI Platform);
      B --> C{CNN Model};
      C -- Task 1 --> D[Automated Tumor Segmentation];
      C -- Task 2 --> E[Tumor Burden Calculation];
      C -- Task 3 --> F[Optimal ¹⁷⁷Lu Dose Prediction];
      D & E & F --> G(Oncologist's Dashboard);
  

1.7. Integration with Emerging Tech: Blockchain for Radiopharmaceutical Supply Chain

• Enabling Description: To ensure the authenticity and quality of radiopharmaceuticals, which have short half-lives and are produced on-demand, this disclosure proposes a blockchain-based tracking system. Each batch of the FAP-targeting precursor (e.g., DOTA-L-A) is assigned a unique hash on a permissioned blockchain. At each step—synthesis, QC testing, radiolabeling at the radiopharmacy, dose calibration, and administration to the patient—a transaction is recorded on the blockchain ledger. This creates an immutable, time-stamped audit trail. Hospitals can scan a QR code on the dose vial to instantly verify its entire lifecycle, confirming it is an authentic product from a licensed manufacturer and that the radioactivity matches the prescribed dose at the time of injection.

• Mermaid.js Diagram: Blockchain Ledger

  sequenceDiagram
      participant Manufacturer
      participant Radiopharmacy
      participant Hospital
      participant Blockchain
      Manufacturer->>Blockchain: Create Batch (Precursor Hash)
      activate Blockchain
      Radiopharmacy->>Blockchain: Record Radiolabeling Event (¹⁷⁷Lu Lot #)
      Radiopharmacy->>Blockchain: Record QC Results
      Hospital->>Blockchain: Record Dose Administration (Patient ID Hash)
      deactivate Blockchain
  

1.8. The "Inverse" or Failure Mode: FAP-alpha Activated Pro-Drug

• Enabling Description: To improve the tumor-to-background ratio and reduce systemic toxicity, this disclosure describes a "pro-drug" therapeutic agent. The cytotoxic payload (B), instead of being a simple radionuclide, is a potent chemotherapeutic agent like a duocarmycin analogue. It is attached via a specialized linker (L) that is specifically cleavable by the enzymatic activity of FAP-alpha. Furthermore, a temporary "caging" group is attached to the cytotoxic agent, rendering it inert. The entire B-L-A compound circulates systemically in its inactive state. Upon reaching a FAP-positive tumor, the FAP-alpha enzyme cleaves the linker, releasing the caged cytotoxic agent. A secondary, tumor-specific condition (e.g., hypoxia or low pH) then cleaves the caging group, activating the payload only within the precise tumor microenvironment. This dual-check system ensures the agent fails safely (remains inert) if it does not localize to the target.

• Mermaid.js Diagram: Activation Sequence

  graph TD
      A[Systemic Circulation <br> (Inactive Prodrug)] -- Step 1: Localization --> B{FAP-alpha+ Tumor};
      B -- Step 2: FAP-alpha enzymatic cleavage --> C[Linker Cleavage <br> (Release of caged payload)];
      C -- Step 3: Tumor Microenvironment <br> (e.g., Hypoxia) --> D[Decaging & Activation];
      D -- Step 4 --> E[Localized Cytotoxicity];
  

Combination Prior Art Scenarios

1. Combination with DICOM Standard: The imaging data (PET, SPECT, CT) generated by the agents described in US 11,938,201 is formatted and transmitted according to the open-source DICOM (Digital Imaging and Communications in Medicine) standard (ISO 12052). This allows for seamless integration with existing hospital Picture Archiving and Communication Systems (PACS) and radiology workstations, making the image analysis interoperable with standard clinical software tools and AI algorithms built on the DICOM framework.

2. Combination with Open Babel Cheminformatics Standard: The chemical structures of all disclosed derivatives, including the quinoline core (A), linkers (L), and functional groups (B), are encoded using the open-source Simplified Molecular-Input Line-Entry System (SMILES) and processed using the Open Babel chemistry toolbox. This enables the creation of searchable chemical databases, facilitates computational modeling of structure-activity relationships (SAR), and allows for the use of open-source software for virtual screening of new targeting moieties or linkers.

3. Combination with TensorFlow/PyTorch for Predictive Modeling: The AI-driven diagnostic and dosimetry system described in derivative 1.6 is built using the open-source TensorFlow or PyTorch machine learning frameworks. The trained CNN models, along with the training and validation scripts, are made publicly available. This allows other researchers to replicate the results, fine-tune the models on their own datasets, and develop new predictive algorithms for FAP-alpha targeted theranostics, thereby rendering minor improvements to the AI model itself as obvious extensions of this work.