Sonnet BioTherapeutics Receives Notice of Allowance for U.S. Patent Covering Composition of Matter of Specific Amino Acid Substitutions of its IL-18 Binding Protein Resistant Variant Protein

Rhea-AI Summary

Sonnet BioTherapeutics (NASDAQ: SONN) has received a Notice of Allowance from the USPTO for a patent covering its modified version of Interleukin-18 (IL-18BPR). The patent specifically covers variant human IL-18 proteins with amino acid substitutions at positions Y1W, Y1K, M51Y, M51S, M60W, S105E, and D110Y.

The company's IL-18BPR demonstrates wild-type binding to the IL-18 receptor while showing undetectable binding to the inhibitory IL-18 Binding Protein, potentially making it more effective. This development strengthens Sonnet's intellectual property position and opens up licensing opportunities independent of their FHAB platform.

Sonnet has developed two drug candidates utilizing this technology: SON-1411, a bifunctional fusion protein combining IL-18BPR with IL-12, and SON-1400, a monofunctional fusion protein. Both are linked to Sonnet's Fully Human Albumin Binding (FHAB) platform, which extends half-life and targets the tumor microenvironment.

Positive

• Patent strengthens intellectual property position for IL-18BPR technology
• New licensing opportunities independent of FHAB platform could generate additional revenue
• Technology shows improved efficacy potential over traditional IL-18 treatments

Negative

• Clinical efficacy of the technology remains to be proven
• Commercialization timeline and potential market impact unclear

Insights

Biotech Patent Strategist

Sonnet BioTherapeutics has secured a critical intellectual property asset with the USPTO's Notice of Allowance for their patent covering the composition of matter of their IL-18 Binding Protein Resistant (IL-18BPR) variant protein. This patent specifically protects the amino acid sequence modifications that enable their IL-18 variant to evade the natural inhibitory protein (IL-18BP) while maintaining normal receptor binding.

For a micro-cap biotech with $4.2 million market capitalization, this patent represents a significant proportion of the company's overall value. The IP protection creates two strategic advantages: first, it strengthens Sonnet's exclusivity around their two pipeline candidates (SON-1411 and SON-1400) that incorporate this technology; second, it opens potential licensing opportunities independent of their FHAB platform technology.

The technical breakthrough addresses a fundamental limitation in IL-18 therapy development. Previous clinical attempts with IL-18 have faltered due to the inhibitory activity of IL-18BP, which effectively neutralizes the cytokine's immunostimulatory effects. By engineering resistance to this inhibition, Sonnet's variant potentially preserves IL-18's ability to activate both innate and adaptive immune responses in the tumor microenvironment.

Sonnet's bifunctional approach with SON-1411 is particularly noteworthy, as it combines the IL-18BPR with IL-12, another potent immunostimulatory cytokine. This synergistic pairing, coupled with their albumin-binding FHAB platform for extended half-life and tumor targeting, represents a differentiated approach in the competitive immuno-oncology landscape.

While this patent strengthens Sonnet's competitive position, investors should recognize that significant development milestones, including clinical validation, remain ahead. The patent's primary value lies in establishing barriers to competition and creating potential future licensing revenue streams rather than generating immediate financial returns.

Immuno-Oncology Specialist

The USPTO's Notice of Allowance for Sonnet's IL-18BPR patent represents a meaningful advancement in cytokine engineering for cancer immunotherapy. By creating IL-18 variants with specific amino acid substitutions that prevent binding to IL-18BP while maintaining IL-18 receptor interactions, Sonnet has potentially solved a fundamental limitation that has hindered IL-18-based therapies.

From an immunological perspective, this approach directly addresses a common tumor immune evasion mechanism. Many cancers overexpress IL-18BP specifically to neutralize endogenous IL-18, which is a critical cytokine for activating natural killer cells and promoting Th1 immune responses essential for anti-tumor immunity. By engineering resistance to this inhibitor, Sonnet's IL-18BPR could potentially maintain immunostimulatory activity even in tumor microenvironments with high IL-18BP expression.

The company's bifunctional approach with SON-1411 leverages established synergy between IL-18 and IL-12. These cytokines operate through complementary but distinct signaling pathways that converge on interferon-gamma production and enhanced cytotoxic lymphocyte activity. The combination has demonstrated superior anti-tumor effects compared to either cytokine alone in numerous preclinical models.

The integration with Sonnet's FHAB technology adds another dimension of potential advantage. By binding to serum albumin, these fusion proteins can achieve extended circulation half-life. More importantly, the FHAB domain's affinity for glycoprotein 60 and SPARC enables preferential accumulation in tumor tissues, where these proteins are often overexpressed. This tumor-targeting capability could help mitigate the systemic toxicity concerns that have historically cytokine therapies.

While this patent strengthens Sonnet's intellectual property position in the competitive cytokine therapeutics landscape, clinical validation will ultimately determine the value of this approach. The engineering of a cytokine to evade its natural inhibitor while preserving receptor binding represents sophisticated protein engineering with potential applications beyond the specific constructs mentioned in the patent.

Company advancing development of its modified version of Interleukin-18 (IL-18^{Binding Protein Resistant} or IL-18^BPR) that exhibits wild-type binding to the IL-18 receptor (IL-18Rc), coupled with undetectable binding to the inhibitory IL-18 Binding Protein (IL-18BP) thus making IL-18^BPR more effective in vitro

Sonnet’s variant human IL-18^BPR is a key cytokine which comprises substitutions at the following amino acid positions: Y1, M51, M60, S105 and D110, relative to human wildtype IL-18

Patent opens up potential licensing opportunities for rights to IL-18^BPR independent of Sonnet’s F_HAB platform patent estate

Management releases “What This Means” segment discussing the allowed patent; Access here

PRINCETON, N.J., March 19, 2025 (GLOBE NEWSWIRE) -- Sonnet BioTherapeutics Holdings, Inc. (the “Company” or “Sonnet”) (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, today announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance to the Company for a second patent in the IL-18 variant protein field which discloses the amino acid sequence of its variant human IL-18^BPR protein. The allowed patent claims cover variant human IL-18 (hIL-18) proteins, including but not limited to hIL-18 proteins having amino acid substitutions at the following positions: Y1W, Y1K, M51Y, M51S, M60W, S105E, and D110Y, relative to human wildtype IL-18. Additionally, the Company announced the release of a Virtual Investor “What This Means” segment to discuss the allowed patent, which is now available here.

“I believe that Sonnet has become of one of the few companies that hold proprietary rights to IL-18^BPR which could be a highly valuable cytokine for cancer patients. This patent covers the composition of matter of the amino acid sequence of our human IL-18^BPR variant protein which bolsters our intellectual property position and provides further validation to our approach that when IL-18^BPR is synergistically combined with IL-12, we believe we will have the potential to develop an important therapeutic asset for oncology and cell-based therapy. Additionally, we feel that this patent enables us to explore opportunities for IL-18^BPR to be licensed independent of our F_HAB platform. We continue to believe that novel bifunctional molecules such as SON-1411, when combined with our proprietary F_HAB platform, have the potential to demonstrate improved tumor targeting, extended half-life and an enhanced therapeutic window,” said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer.

Sonnet previously reported the generation of two novel drug candidates, SON-1411 (IL18^BPR-F_HAB-IL12) and SON-1400 (IL18^BPR-F_HAB), each containing a variant version of recombinant human interleukin-18 (IL-18^BPR). SON-1411 is a proprietary bifunctional fusion protein consisting of IL-18^BPR combined with single-chain wild-type IL-12, linked to Sonnet's Fully Human Albumin Binding (F_HAB^®) platform while SON-1400 is a monofunctional fusion protein comprising the same IL-18^BPR domain linked to the F_HAB. F_HAB extends the half-life and biological activity of linked molecules by binding native albumin in the serum and targets the tumor microenvironment (TME) through high affinity binding to glycoprotein 60 (gp60) and the Secreted Protein Acidic and Rich in Cysteine (SPARC).

“SON-1411 (IL18^BPR-F_HAB-IL12) is a bifunctional combination of IL-12 and the F_HAB domain with a human variant of human interleukin-18 (“IL-18^BPR”), which was modified to resist an inhibitory interaction with IL-18 binding protein (IL-18BP). IL-18 is involved in activating both innate and adaptive immune responses; however, IL-18 clinical therapies have been hampered by a lack of efficacy due to the inhibitory activity of the IL-18BP,” commented John Cini, Ph.D., Sonnet Chief Scientific Officer.

About SON-1411

SON-1411 is a candidate immunotherapeutic recombinant drug that is closely related to and will replace SON-1410, which links an unmodified single-chain human IL18 and an unmodified IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. The only difference between SON-1410 and SON-1411 is that in the latter, the IL-18 domain has been modified via mutagenesis to retain wildtype binding to the IL-18 receptor (IL-18 Rc) while inhibiting or abolishing binding to the IL-18 binding protein (IL-18 BP). The A10m3 scFv was selected to bind both at normal pH, as well as at the acidic pH that is typically found in the TME. The F_HAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of IL-18 and IL-12, as well as a variety of potent immunomodulators that can be added using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as SPARC and gp60, several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1411 is designed to deliver IL-18^BPR and IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

About Sonnet BioTherapeutics Holdings, Inc.

Sonnet is an oncology-focused biotechnology company with a proprietary platform for developing targeted biologic drugs with single or bifunctional action. Known as F_HAB (Fully Human Albumin-Binding), the technology utilizes a fully human single chain antibody fragment (scFv) that binds to and "hitch-hikes" on human serum albumin (HSA) for transport to target tissues. Sonnet's F_HAB was designed to specifically target tumor and lymphatic tissue, with an improved therapeutic window for optimizing the safety and efficacy of immune modulating biologic drugs. F_HAB platform is the foundation of a modular, plug-and-play construct for potentiating a range of large molecule therapeutic classes, including cytokines, peptides, antibodies, and vaccines.

Sonnet’s lead program, SON-1010, or IL-12-F_HAB, is in development for the treatment of advanced solid tumors, certain types of sarcoma, and platinum-resistant ovarian cancer (PROC). SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement with Roche in combination with atezolizumab (Tecentriq^®) for the treatment of PROC. The Company is also evaluating its second product candidate, SON-1210, an IL12-F_HAB-IL15 bifunctional for solid tumors, in collaboration with the Innovative Immuno-Oncology Consortium (IIOC), and plans to commence an investigator-initiated and funded Phase 1/2a study for the treatment of locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).

The Company’s SON-080 program is a low dose of rhIL-6 in development for Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Diabetic Peripheral Neuropathy (DPN). SON-080 demonstrated encouraging results in a Phase 1b/2a clinical trial, being well tolerated with no evidence of a pro-inflammatory cytokine response. In October 2024, Sonnet announced a license agreement with Alkem Laboratories, Inc. who will assume responsibility for advancing development of the SON-080 program into a Phase 2 study in DPN in India.

Forward-Looking Statements

This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the impact of the second patent in the IL-18 variant protein field, outcome of the Company’s clinical trials, the Company's cash runway, the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions.

These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential, "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Investor Relations Contact:
JTC Team, LLC
Jenene Thomas
908-824-0775
SONN@jtcir.com 

FAQ

What is the significance of Sonnet's new IL-18BPR patent for SONN stock?

The patent strengthens Sonnet's intellectual property position and opens new licensing opportunities independent of their FHAB platform, potentially creating additional revenue streams.

How does Sonnet's IL-18BPR technology differ from traditional IL-18 treatments?

IL-18BPR shows wild-type binding to IL-18 receptor with undetectable binding to inhibitory IL-18BP, making it potentially more effective than traditional IL-18 treatments.

What are the key drug candidates developed with Sonnet's IL-18BPR technology?

SON-1411 (bifunctional fusion protein with IL-12) and SON-1400 (monofunctional fusion protein), both linked to the FHAB platform.

What specific amino acid substitutions are covered in Sonnet's new patent?

The patent covers Y1W, Y1K, M51Y, M51S, M60W, S105E, and D110Y substitutions relative to human wildtype IL-18.