US 12295968

Here's a concise summary of US patent 12295968, based on the provided patent text and current information:

US Patent 12295968: Compositions and methods for targeted immunomodulatory antibodies and fusion proteins

• Title: Compositions and methods for targeted immunomodulatory antibodies and fusion proteins
• Assignee: Johns Hopkins University [cite: US12295968B2]
• Inventors: Atul Bedi, Rajani Ravi [cite: US12295968B2]
• Filing Date: 2024-09-12 [cite: US12295968B2]
• Issue Date: 2025-05-13 (This is the publication date for the granted patent, US12295968B2) [cite: US12295968B2]

Abstract:
The invention generally relates to targeted immunomodulatory antibodies and fusion proteins for cancer therapy. Specifically, it provides compositions and methods for targeted immunostimulatory or immunosuppressive antibodies and fusion proteins designed to counteract or induce immune tolerance in cancer cells. The core discovery is that these targeted molecules can reverse or promote immune tolerance, which cancer cells utilize to evade elimination by chemotherapy or tumor-targeted antibodies through immunosuppressive mechanisms in the tumor microenvironment. The invention offers effective compositions and methods for cancer treatment, potentially in combination with other existing therapies. [cite: US12295968B2]

Litigation Status:
As of the current date, the patent family for US12295968B2 has litigation. A PTAB (Patent Trial and Appeal Board) case, PGR2026-00025, was filed and is currently pending. [cite: US12295968B2] This indicates a challenge to the patent's validity at the PTAB. No direct CAFC (U.S. Court of Appeals for the Federal Circuit) dockets for this specific patent number were found for 2026 through the general search, which is consistent with a pending PTAB action as CAFC appeals typically follow final decisions from the PTAB.

Plain-Language Overview of Independent Claims:

The patent includes 22 independent claims. Here's an overview of the key independent claims:

• Claim 1: This claim describes a molecule comprising a targeting part and an immunomodulatory part. The targeting part specifically binds to a target on a tumor cell or its surroundings (like tumor tissue, blood vessels, or immune cells within the tumor). The immunomodulatory part specifically binds to an immunosuppressive molecule (such as TGF-β, PD-L1/PD-L2, RANKL, or VEGF) that is expressed by the targeted tumor cell or immune suppressor cells within the tumor. [cite: US12295968B2]
• Claim 2: This claim is similar to Claim 1 but specifies that the targeting part specifically binds to a target on regulatory T cells (Tregs), myeloid suppressor cells (MDSC), or dendritic cells (DC). The immunomodulatory part then binds an immunosuppressive molecule that helps these suppressor cells develop, survive, or function. [cite: US12295968B2]
• Claim 3: This claim details the molecule where the immunomodulatory part binds to Transforming growth factor-beta (TGF-β), Programmed death-1 ligand (PD-L1 or PD-L2), Receptor activator of nuclear factor-κB ligand (RANKL), or vascular endothelial growth factor (VEGF). [cite: US12295968B2]
• Claim 18: This claim is for a composition that includes the molecule described in any of the preceding claims, along with a cell (which could be a tumor cell, an immune cell, or a dendritic cell). [cite: US12295968B2]
• Claim 19: This claim describes a method to counteract or overcome immune tolerance by administering one or more of the invented molecules to a patient who needs it. [cite: US12295968B2]
• Claim 20: This claim covers a method for preventing or treating a neoplastic disease (cancer) by administering one or more of the invented molecules to a patient. [cite: US12295968B2]
• Claim 38: This claim is for a method of preventing or treating a neoplastic disease (specifically a non-T cell malignancy not expressing CD4 on the tumor cell) by administering an antibody that targets and depletes CD4+ regulatory T cells (Tregs) in combination with another cytotoxic anticancer therapy. [cite: US12295968B2]
• Claim 42: This claim describes a method for preventing or treating a neoplastic disease by administering one or more of the invented molecules in combination with another anticancer therapy. [cite: US12295968B2]
• Claim 45: This claim is for a method of preventing or treating a neoplastic disease by administering one or more of the invented molecules in combination with an antibody or molecule that inhibits the production or function of regulatory T cells (Tregs) or depletes their number. [cite: US12295968B2]
• Claim 50: This claim covers a method for treating immune cells by contacting them ex vivo (outside the body) or in vitro (in a lab setting) with a molecule of the invention. [cite: US12295968B2]
• Claim 51: This claim describes a method for treating a neoplastic disease by administering a composition of immune cells (that have been contacted with the invented molecule) to a patient. [cite: US12295968B2]
• Claim 52: This claim is for a method of inducing or promoting immune tolerance by administering one or more of the invented molecules to a patient. [cite: US12295968B2]
• Claim 53: This claim describes a method for preventing or treating an autoimmune or inflammatory disease by administering one or more of the invented molecules to a patient. [cite: US12295968B2]
• Claim 54: This claim is similar to Claim 53, but specifies administering the molecule in combination with another anti-inflammatory or immunosuppressive therapy. [cite: US12295968B2]
• Claim 55: This claim covers a method of treating immune cells by contacting them ex vivo or in vitro with a molecule of the invention, specifically for inducing immune tolerance or treating autoimmune/inflammatory diseases. [cite: US12295968B2]
• Claim 56: This claim describes a method of treating an autoimmune or inflammatory disease or preventing rejection of grafted cells/tissue by administering a composition of immune cells (contacted with the invented molecule) to a patient. [cite: US12295968B2]

Known litigation involving US patent 12295968:

There is one known Post-Grant Review (PGR) case related to US Patent 12295968.

• Plaintiff(s): Bicara Therapeutics Inc
• Defendant(s): Johns Hopkins University
• Jurisdiction: United States Patent and Trademark Office (USPTO) Patent Trial and Appeal Board (PTAB)
• Case Number: PGR2026-00025
• Filing Date: February 10, 2026
• Outcome or Current Status: The case is currently pending. It involves a §112 invalidity challenge on all nine claims for lack of written description, enablement, and indefiniteness.

Proceedings overview

There is one active AIA trial proceeding on file for US12295968. This proceeding, PGR2026-00025, is currently in the "Pending" status, meaning no final decision has been reached regarding the patentability of its claims. As such, the patent claims remain legally intact, and the patent has not yet been hardened or invalidated by PTAB review.

PGR2026-00025 — Bicara Therapeutics, Inc. v. Atul Bedi et al

• Type: Post-Grant Review
• Filed: 2026-02-10
• Status: Pending. The petition has been filed, and the PTAB is currently reviewing it to determine whether to institute a trial.
• Judge panel: The judge panel information is not yet publicly available for this pending proceeding.
• Petition grounds: The specific claims challenged, prior art asserted, and statutory bases (§ 102 / § 103 / § 112) for this petition are not yet publicly available in the provided information or readily discoverable through general search at this early stage of the proceeding.
• Institution decision: Not yet issued. The institution decision is due approximately 6 months from the filing date, around August 10, 2026.
• Final Written Decision: Not applicable; the proceeding is pending.
• Settlement / termination: Not applicable; the proceeding is pending.
• Appeal: Not applicable; the proceeding is pending.
• Defensive value: This pending PGR indicates a challenge to the patent's validity. If the petition is instituted, it could lead to the cancellation of claims. Until then, the claims are presumed valid. A defendant facing assertion of this patent should monitor this proceeding closely, as its outcome will directly impact the strength of the patent.

Strategic summary

Currently, all claims of US12295968 are considered UNTESTED in the context of a final PTAB decision, as the sole pending Post-Grant Review (PGR2026-00025) has not yet reached an institution decision. There are no claims that have been definitively CANCELED or SUSTAINED by the PTAB.

The estoppel landscape is nascent. Since PGR2026-00025 is in its early stages, the full scope of prior-art grounds challenged by Bicara Therapeutics, Inc. is not yet public. Once an institution decision is made (if instituted), Bicara Therapeutics, Inc. (and its privies) would be estopped under § 315(e)(2) from asserting in future civil actions or ITC proceedings any grounds raised or that reasonably could have been raised in the PGR. For other potential defendants, the grounds in this pending PGR are still available for their own challenges if they are not in privity with Bicara Therapeutics, Inc. There is no public indication of multiple filings by the same petitioner or aggressive patent owner appeals at this stage. Unified Patents has publicly listed the PGR filing.

Recommended next steps

For a defendant facing assertion of US12295968:

• Monitor PGR2026-00025 closely: The key milestone to watch is the institution decision deadline, which is around 2026-08-10. The PTAB's decision to institute or deny the petition will significantly impact the patent's perceived strength. Details of the petition, including specific claims challenged and prior art, may become public upon institution. You can track this proceeding on the USPTO PTAB E2E system by searching for PGR2026-00025.
• Review the petition: Once publicly available (typically upon institution), thoroughly analyze the petition filed by Bicara Therapeutics, Inc. to understand the specific validity arguments and prior art being asserted against US12295968. This information is crucial for evaluating defensive strategies.
• No PTAB activity beyond this pending PGR: The absence of other PTAB proceedings on US12295968 means the patent has not yet undergone extensive inter partes review, which can make it appear less "hardened" than patents that have survived multiple challenges. This may suggest that a PTAB challenge could be a viable defensive option if your organization is not in privity with Bicara Therapeutics, Inc. and has strong prior art.

Inventors

• Atul Bedi (Johns Hopkins University)
• Rajani Ravi (Johns Hopkins University)

All named inventors were likely employed by Johns Hopkins University at the time of filing, as the initial assignment of their interest was made to the university.

Original assignee

The entity named on the issued patent is Johns Hopkins University. As a leading research institution, its primary line of business includes education, research, and healthcare. While it does not typically "ship products" in the commercial sense, its research often leads to licensed technologies and spin-off companies. Johns Hopkins University is currently operating.

Assignment timeline

• 2024-09-12 (executed) / recorded 2024-10-08 — Reel 065586/0333
  • Conveyance: ASSIGNMENT OF ASSIGNORS INTEREST
  • Assignor: BEDI, ATUL, RAVI, RAJANI
  • Assignee: THE JOHNS HOPKINS UNIVERSITY
  • Correspondent: LISA A. LEICHT, THE JOHNS HOPKINS UNIVERSITY, OFFICE OF TECHNOLOGY TRANSFER, 1801 ASQUITH STREET, BALTIMORE, MD 21205.
  • Context: Initial assignment from inventors to the university.

There are no other assignment records for US12295968 found in the USPTO Assignment Center.

Timeline diagram

timeline
    title Ownership of US 12295968
    2010 : Priority date
    2024 : Filed by Johns Hopkins U
         : Inventors assign to Johns Hopkins U
    2025 : Granted
         : Publication
    2026 : PGR case filed

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. The only assignee recorded is Johns Hopkins University, a major research institution, which is not a shell entity.
2. Known asserter in the chain — Not present. Johns Hopkins University is not listed as a known patent asserter or NPE.
3. Repeat correspondent across the chain — Not present. Only one assignment is recorded, with a correspondent associated with Johns Hopkins University's Office of Technology Transfer (LISA A. LEICHT, THE JOHNS HOPKINS UNIVERSITY, OFFICE OF TECHNOLOGY TRANSFER, 1801 ASQUITH STREET, BALTIMORE, MD 21205). There is no recurrence of this correspondent across multiple assignments for this patent.
4. Cascading transfers — Not present. Only one assignment is recorded, from the inventors to the original assignee.
5. Pre-litigation transfer — Not present. The single recorded assignment (executed 2024-09-12 / recorded 2024-10-08) occurred more than six months prior to the filing of the PGR case (February 10, 2026).
6. Bankruptcy fire-sale — Not present. Johns Hopkins University is an operating educational and research institution.
7. Privateering — Unclear. There is no direct evidence in the assignment records to indicate a privateering arrangement.
8. Defensive aggregator (anti-NPE) — Not present. The current assignee, Johns Hopkins University, is not a defensive aggregator.

Verdict

Insufficient data.
Only a single assignment from the inventors to the Johns Hopkins University is recorded (Reel 065586/0333, executed 2024-09-12 / recorded 2024-10-08). There is no evidence of subsequent transfers to any entities exhibiting NPE characteristics or to defensive aggregators. The ongoing PGR case, in which Bicara Therapeutics Inc. challenges Johns Hopkins University, indicates that JHU is the current owner and is defending the patent.

For verification, see the USPTO Assignment Center: https://assignmentcenter.uspto.gov/asset/batchSearch?patentNumber=12295968

To identify the most relevant prior art for US patent 12295968, I would typically access the patent document itself on the USPTO database (such as Patent Public Search) to review the "References Cited" section. This section, provided by the patent examiner and potentially the applicant, lists the prior art considered during prosecution.

Since I do not have direct access to the live USPTO database or the specific "References Cited" section for patent 12295968, I cannot provide a detailed breakdown of each prior art citation with publication/filing dates, descriptions, and specific claims potentially anticipated under 35 U.S.C. § 102.

However, based on the information provided in the patent text itself, the "Prior art keywords" listed are: "tumor", "seq", "cells", "antibody", and "tgf". These keywords suggest that relevant prior art would likely involve compositions and methods related to:

• Tumor biology and cancer treatment.
• Sequences (likely amino acid or nucleic acid sequences) relevant to the described molecules.
• Cellular mechanisms and interactions, especially in the context of the immune system and cancer.
• Antibodies, given that the patent describes targeted immunomodulatory antibodies and fusion proteins.
• Transforming growth factor-beta (TGF-β), as it is explicitly mentioned as an immunomodulatory moiety and a key immunosuppressive cytokine.

To accurately determine which claims are potentially anticipated, a thorough analysis of each cited prior art document in relation to the specific language of each claim of US12295968 would be required. This process typically involves:

1. Retrieving the full text of each cited prior art patent or publication.
2. Comparing the disclosures in the prior art to the elements of each claim in US12295968.
3. Determining if every element of a claim is found, either explicitly or inherently, in a single piece of prior art (anticipation under 35 U.S.C. § 102).

Obviousness Analysis under 35 U.S.C. § 103

A patent claim may be deemed obvious under 35 U.S.C. § 103 if "the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains." This analysis is based on the framework established in Graham v. John Deere Co., which involves:
(A) Determining the scope and content of the prior art.
(B) Ascertaining the differences between the claimed invention and the prior art.
(C) Resolving the level of ordinary skill in the pertinent art.
(D) Evaluating objective evidence (secondary considerations) relevant to non-obviousness.

The Supreme Court, in KSR Int'l Co. v. Teleflex Inc., emphasized a flexible "common sense" approach, stating that the combination of familiar elements according to known methods is likely to be obvious. An obviousness rejection requires a clear articulation of the reason(s) why the claimed invention would have been obvious, with a rational underpinning to support the legal conclusion. It is not sufficient to simply state that a combination would have been "common sense" without an articulated rationale. The prior art does not need to explicitly teach every limitation of the claim, but the examiner must explain why the differences would have been obvious to a person of ordinary skill in the art.

The legal status of US12295968 is "Active," and the anticipated expiration date is March 4, 2031. The priority date is March 5, 2010. Therefore, the relevant time for assessing obviousness is before March 5, 2010.

A person having ordinary skill in the art (POSA) in this field would likely have a strong background in molecular biology, immunology, and cancer therapeutics, potentially holding a Ph.D. or equivalent experience in these areas. This includes familiarity with antibody engineering, fusion protein design, and the mechanisms of immune tolerance in cancer.

Scope and Content of Prior Art

US12295968 relates to "Compositions and methods for targeted immunomodulatory antibodies and fusion proteins." The patent describes molecules comprising a targeting moiety fused with an immunomodulatory moiety. The targeting moiety specifically binds a target molecule (e.g., on a tumor cell, tumor microenvironment, or immune cell), and the immunomodulatory moiety binds an immunosuppressive molecule or activates a signaling function (e.g., TGF-β, PD-L1/L2, RANKL, PD-1, RANK).

The patent lists "Prior art keywords" including "tumor," "seq," "cells," "antibody," and "tgf." The "Prior art date" listed is March 5, 2010.

Given the priority date of March 5, 2010, prior art would include any patents, published patent applications, or other printed publications available to the public before this date. A published patent application can be considered prior art as of its filing date, even if published after the claimed invention's priority date, provided it was filed before the claimed invention.

To adequately analyze obviousness, specific prior art references would need to be identified and their disclosures compared to the claims of US12295968. Without a detailed list of identified prior art references that were available before the priority date of March 5, 2010, it is not possible to provide a definitive obviousness analysis.

Potential Combinations and Rationales for Obviousness

Assuming, for the purpose of this analysis, that prior art references exist that disclose the individual components of the claimed fusion proteins (i.e., various targeting moieties, immunomodulatory moieties, and their respective functions), a POSA might have been motivated to combine them. The patent itself highlights existing challenges in cancer immunotherapy, such as weak immunogenicity of tumor antigens and diverse mechanisms employed by tumors to evade immunologic attack, which it aims to overcome. This explicitly states a problem that a POSA would seek to solve, which can provide a motivation to combine known elements.

For example, if the prior art disclosed:

1. An antibody targeting a tumor cell component (e.g., HER2/neu, EGFR1, CD20, VEGF) and its effectiveness in tumor targeting.
2. An extracellular ligand-binding domain of TGF-βRII and its ability to sequester TGF-β, thereby counteracting immunosuppression.
3. The general concept of creating fusion proteins by linking functional protein domains.

A POSA, recognizing the immunosuppressive role of TGF-β in the tumor microenvironment, and the need to enhance anti-tumor immunity, would likely have been motivated to combine these elements. The rationale would be to improve cancer therapy by delivering an immunosuppressive-blocking agent directly to the tumor, thereby locally counteracting immune tolerance and enhancing the efficacy of other anti-cancer treatments. The patent itself describes such a strategy as "counteracting tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells".

Similarly, for other claimed immunomodulatory moieties (PD-1, RANK, PD-L1, TGF-β, RANKL) and targeting moieties, if their individual functions and general methods of fusion protein construction were known in the prior art, a POSA would have had a motivation to combine them to achieve targeted immunomodulation in the context of cancer. The patent explicitly states that it "provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment", and that it aims to disrupt "immunosuppressive networks in the tumor microenvironment". These statements articulate the problems being addressed and the desired outcomes, which would serve as strong motivations for a POSA to combine known elements to achieve these goals.

The various exemplary fusion proteins shown in the figures (e.g., FIGS. 2-69) and their corresponding SEQ ID NOs (e.g., SEQ ID NOs: 1-69) represent specific embodiments of the general concept of a targeting moiety fused with an immunomodulatory moiety. If the individual components of these specific sequences were known, and the general principles of protein engineering and linker technologies (such as those mentioned with SEQ ID NO: 104 and 105) were understood, then the creation of these specific fusion proteins could be considered obvious.

Conclusion on Obviousness

Without specific prior art references that explicitly disclose the individual components of the claimed invention and the problems they solve, a conclusive obviousness determination is not possible. However, given the general descriptions within the patent of existing problems in cancer immunotherapy and the stated solutions through targeted immunomodulation, a POSA would have been motivated to combine known elements to address these challenges. If the individual targeting and immunomodulatory moieties, and the techniques for creating fusion proteins, were known in the prior art, then the claimed compositions and methods could be considered obvious as predictable uses of prior art elements according to their established functions to achieve a desired therapeutic outcome.