CD147 Competitive Landscape

The CD147 IP landscape is well-populated, evolving from early murine/chimeric mAbs for oncology to sophisticated engineered antibodies and cell therapies. Key assignees include academic institutions (e.g., Fourth Military Medical University - FMMU for HAb18) and biopharma (Abgenix/Amgen, Centocor/J&J, CytomX, Daiichi Sankyo, Ibex Biosciences). Patent types cover composition of matter (sequences, ADCs, CARs), method of use (cancer, infectious diseases, inflammation), engineered constructs, and diagnostics.

Patent Assignee Distribution (Illustrative)

Note: Chart data is illustrative based on report mentions and not exhaustive.

Table 1: Key CD147 Patents (Excluding WO2022150759A1)

WO2022150759A1 (Ibex Biosciences, VhH platform) has entered national phases (US, EP, CN, JP, AU, CA, KR). Daiichi Sankyo's CN111051513A (CD147 signaling activators) is also in prosecution. CytomX's US20180303952A1 (activatable Abs) is abandoned, but related applications may exist. Prosecution histories offer insights into inventive aspects and evolving IP.

This application covers a VhH (nanobody) antibody platform targeting CD147 for naked antibodies, ADCs, and CARs (CAR-T/NK).

• Key Claims: Specific VhH sequences (SEQ ID NOs: 4-15) and CDRs (SEQ ID NOs: 16-39) with ≥70% identity. Exemplified: Ibx-11, Ibx-13, Ibx-75, Ibx-76, Ibx-77. Covers various antibody formats, CAR constructs, and ADCs with diverse payloads.
• Functional Properties/Indications:
  • Anti-viral (SARS-CoV-2, measles, HIV, influenza) by blocking CD147 interaction.
  • Anti-malarial (Ibx-13 reduces *P. falciparum* parasitemia *in vitro*).
  • Anti-cancer (Ibx-11/Ibx-13 ADCs kill MiaPaCa-2 cells; Ibx-76/77 inhibit angiogenesis).
  • Anti-inflammatory/autoimmune.
• Experimental Support: Specific binding of Ibx-11, Ibx-13, Ibx-77 to human CD147 (not murine). Ibx-77 $K_D$: 138.0 nM (steady state) / 36.1 nM (kinetic).
• Strengths: VhH platform advantages (size, stability, versatility). Broad indications.
• Vulnerabilities: Broad initial claims in crowded fields (e.g., cancer) may face prior art challenges. Novelty of specific VhH sequences and functional attributes vs. existing binders is key. More *in vivo* data needed for ADCs/CARs.

Ibex should pursue a multi-faceted strategy:

• Deepen Composition of Matter claims for specific VhH domains with detailed characterization.
• Develop and patent specific ADC embodiments (VhH-linker-payload) with *in vivo* data.
• Refine CAR-T/NK constructs with specific co-stimulatory domains, safety switches, and comparative data.
• Strengthen Method of Use claims with robust preclinical/clinical data for specific diseases (e.g., malaria, specific viruses, cancer subtypes).
• File for combination therapy patents.
• Explore and patent diagnostic applications (e.g., radiolabeled VhH).
• Protect novel formulations and manufacturing processes.
• Maintain broad geographical patent filings.
• Clearly articulate novelty and non-obviousness against prior art.

The CD147 space has significant patent activity. Potential conflicts exist with:

• Dominant/Crowded Areas: Conventional mAbs (Abgenix, FMMU), glycoengineered Abs (FMMU's Metuzumab), signaling modulators (Daiichi Sankyo), activatable Abs (CytomX), CAR-T/NK (Central South Uni., academic/NIH), small molecules (CN201310574056).
• FTO for Ibex (WO2022150759A1): Depends on novelty of VhH sequences/epitopes. For ADCs, linker/payload IP matters. For CARs, VhH domain and CAR architecture uniqueness are key. Broad use claims will face prior art; specific, data-supported claims are better. Anti-malarial/viral VhH applications might have more FTO latitude. Detailed FTO analysis per product is crucial.

• Mechanism of Action Elucidation:
  • Signaling Pathways: CD147 involved in CD147/ERK1/2/STAT3/MMP-2 (HCC, targeted by AC-73), TRAF6-IKK-IRF5 (atherosclerosis), PI3K/Akt-GSK3β (cisplatin resistance in ovarian cancer).
  • CD147 Dimerization: Critical for tumor progression; targeted by AC-73.
  • Interaction with Cyclophilins (CypA/CypB): Crucial for inflammation, viral entry (SARS-CoV-2), atherosclerosis; targeted by SP-8356.
• Role in Chemoresistance: CD147 linked to chemoresistance (e.g., Metuzumab enhances gemcitabine sensitivity in NSCLC). Mechanisms involve DNA damage repair or drug efflux.
• Metabolic Reprogramming in Cancer: Interacts with MCT1/MCT4 to facilitate lactate efflux, supporting Warburg effect.
• Fibrosis: Induces myofibroblast differentiation and ECM deposition. AC-73 reduces intestinal fibrosis.

• Targeting CD147 Dimerization: Small molecules like AC-73 offer a novel approach.
• Logic-Gated CAR Therapies: synNotch systems (e.g., GPC3/CD147 for HCC) enhance specificity and safety.
• Targeting Myeloid Cell CD147: Anti-CD147 Abs show preclinical efficacy in atherosclerosis by targeting myeloid cell functions.

• CD147 Isoform Specificity: Targeting disease-associated isoforms could improve therapeutic index. Less focus currently.
• Combination with Metabolism-Targeted Therapies: Synergistic potential with glycolysis inhibitors, etc., relatively underexplored.
• CD147 in Non-Oncology Inflammatory Diseases: Broader clinical development for common autoimmune/chronic inflammatory diseases (RA, IBD) seems less advanced.
• Targeting CD147 in TME Beyond MMP Induction: Modulating other stromal components, immune interactions, and immunotherapy resistance.

CD147 development involves academic-industry collaborations, licensing, and acquisitions. FMMU collaborated with Chengdu Hoist Biotech (Licartin) and Pacific Meinuoke (Metuzumab). Abgenix (Gavilimomab) was acquired by Amgen. University of Oxford partners with Novavax for the RH5 malaria vaccine. Ibex Biosciences is developing its VhH platform. Daiichi Sankyo and CytomX are other notable players. Recent high-profile licensing deals specifically for novel CD147 *therapeutics* were not prominent in provided 2020-2025 news.

Actionable Insights for WO2022150759A1 (Ibex Biosciences):

• Leverage VhH-specific advantages (size, stability, penetration, manufacturing).
• Prioritize indications with strong preclinical PoC and differentiation (e.g., anti-infectives like malaria/viral; specific oncology niches).
• Advance ADC development with novel, specific VhH-linker-payload constructs and robust *in vivo* data.
• Innovate in CAR-T/NK design to show benefits over scFv-CARs; incorporate safety mechanisms.
• Maintain FTO vigilance and pursue strategic patenting (narrower, data-supported claims).

General Competitive Positioning for CD147 Therapeutics:

• Mechanism of Action Differentiation (e.g., signaling activators, dimerization disruptors).
• Focus on Safety and Therapeutic Window (e.g., activatable platforms, inducible CARs).
• Biomarker-Driven Patient Selection, especially in oncology.

Future Outlook:

• More sophisticated biologics (bispecifics, trispecifics, conditionally activated).
• Advanced cellular therapies (novel CAR designs, safety switches, logic gates, allogeneic).
• Combination strategies with other modalities.
• Expansion into non-oncology indications (infectious diseases, inflammatory/autoimmune).
• Small molecule innovation (oral bioavailability, diverse mechanisms).

Success hinges on efficacy and safety, addressing CD147's physiological expression. For Ibex, leveraging VhH advantages for differentiated products in well-chosen indications is key.