From Patent Sequence to Peer-Reviewed Study: Tracing CB5005 Across the Research Record

The defensible conclusion is specific: CB5005 progressed from a patent-defined peptide into several peer-reviewed preclinical formulation and delivery studies, but the record does not establish human safety, efficacy, regulatory approval, or current legal or commercial status.

The record begins with a November 9, 2004 provisional filing. The patent family disclosed a 21-amino-acid peptide, inventor-reported cell experiments, and claims later granted in U.S. Patent 7,408,022. Patent issuance established legal claims, not treatment validation.

Studies published from 2016 through 2020 examined CB5005-related systems in cells, tumor spheroids, and mice. These papers added peer-reviewed evidence while remaining entirely preclinical.

The 2022 study concerned CB5005N, an 11-residue nuclear-localization derivative used in a liposomal system—not the full 21-residue CB5005 peptide. Its findings should not be presented as a direct replication of full-length CB5005 research.

The CB5005 research record begins with a patent filing, not a peer-reviewed paper. The earliest identified filing was a U.S. provisional application dated November 9, 2004. Its sequence disclosures and experimental examples subsequently entered the public patent record, followed years later by peer-reviewed studies that examined CB5005 in drug-delivery systems and preclinical cancer models.

That chronology matters because a patent and a research paper answer different questions. A patent describes an invention and defines claims for which legal protection is sought. A peer-reviewed article reports experiments evaluated through a journal’s editorial process. Neither format, by itself, demonstrates clinical safety or efficacy. Tracing CB5005 therefore requires attention not only to dates and titles, but also to what each document can establish.

The patent family begins in 2004

The CB5005-related patent family identifies U.S. provisional application 60/626,163, filed on November 9, 2004. That filing was followed by U.S. application 11/270,295 and international application PCT/US2005/040534, both titled “Composition and method for increasing apoptosis in cancer cells.” The patent record names Yao-Zhong Lin and Claudia Budu as inventors and Celtek Bioscience, LLC as assignee.

The U.S. application was published as US 2006/0099275 A1 on May 11, 2006. The international application appeared as WO 2006/053015 A2 on May 18, 2006, with a later A3 publication dated March 29, 2007. These were related public disclosures within one patent family, not three independent biological studies.

U.S. application 11/270,295 issued as U.S. Patent 7,408,022 B2 on August 5, 2008. Its claims concern specified cell-permeable peptides containing the patent-described 11-residue sequence and an NF-κB nuclear-localization sequence. A continuation application, U.S. 12/185,766, was published as US 2009/0155905 A1 on June 18, 2009; Google Patents identifies that continuation as abandoned.

For historical status, Google Patents currently labels U.S. Patent 7,408,022 “Expired – Lifetime” and the associated international case as ceased. Those database labels are useful for reconstructing the record, but they are not a jurisdiction-specific legal opinion, freedom-to-operate analysis, or official clearance determination.

What sequence did the patent identify as CB5005?

The patent identifies CB5005 as SEQ ID NO: 4, a synthetic peptide containing 21 amino acids. Its architecture joins an 11-residue cell-permeable segment to an NF-κB p50-derived nuclear-localization sequence. The same document describes related peptides designated CB5002, CB5003, and CB5007, which served as comparators or controls in the disclosed experiments.

Mechanistically, the design combines two propositions. The first is that one segment can support cellular entry. The second is that the attached p50-derived sequence can influence intracellular NF-κB-related biology. These propositions should not be collapsed into a single claim that the peptide simply “enters cells and works.” Cell-surface association, internalization, subcellular localization, target engagement, and a downstream phenotype are distinct experimental stages. The broader design and evidence are examined in this explanation of CB5005 and NF-κB targeting.

The patent specification describes inventor-reported experiments in DU145, PC3, LNCaP, and N2a cells. The reported work included peptide-uptake observations, nuclear p50 measurements, apoptosis-associated assays, and experiments combining peptides with cisplatin, etoposide, or TNF-α. It also compared CB5005 with SN50 under specified in-vitro conditions and reported stronger effects for CB5005 in those experiments.

Those examples are scientifically relevant because they show the experimental rationale disclosed with the invention. They should nevertheless be described as patent data, not as independently replicated findings or clinical evidence. Even a positive cell-culture result can reflect concentration, exposure duration, cell type, assay design, or nonspecific toxicity. Establishing persistent NF-κB pathway activity and dependence requires more than one positive readout, as discussed in the evidence needed to assess constitutive NF-κB activation.

The record moves into peer-reviewed preclinical research

A later phase of the record begins in 2016, when Zhang and colleagues published a study in Acta Biomaterialia examining CB5005 in combination with doxorubicin. The experiments included brain-endothelial and U87 glioma-cell systems, tumor spheroids, and mouse studies. Yao-Zhong Lin was listed as an author, and the publication record included affiliations with Tongji University and Celtek Bioscience. The PubMed record for the 2016 study documents a peer-reviewed preclinical investigation, not a human trial.

This paper extended the research question beyond the patent’s initial cell experiments. It evaluated CB5005 in a delivery-oriented context involving a second agent and increasingly complex models. A spheroid can reproduce some three-dimensional barriers absent from a monolayer culture, while a mouse experiment can address distribution and tumor-model outcomes that a dish cannot. Neither model fully predicts human pharmacology, toxicity, or therapeutic benefit.

In 2018, another Zhang and colleagues paper, published in the Journal of Controlled Release, evaluated CB5005-conjugated, doxorubicin-loaded PEGylated liposomes. The work included cell, spheroid, and mouse glioma models. Yao-Zhong Lin was again an author, with the publication record listing affiliations that included Tongji University and Celtek Bioscience, LLC. Reported delivery and survival observations came from preclinical models. The 2018 PubMed entry provides the paper’s bibliographic record and abstract.

The conjugated liposome is not experimentally interchangeable with free CB5005. Attaching a peptide to a nanoparticle changes the construct’s size, valency, surface properties, distribution, and uptake behavior. The liposome also carries a pharmacologically active cargo. A result obtained with the complete formulation therefore cannot automatically be assigned to the peptide alone. This is a general feature of cell-penetrating peptide research: cargo size and construct architecture can change delivery behavior.

A 2020 Molecular Pharmaceutics paper by Hu and colleagues examined irinotecan-loaded liposomes modified with CB5005. Its experiments used A549 cells and mouse xenografts, and Yao-Zhong Lin was listed with a Celtek Bioscience affiliation. The study reported tumor-penetration and NF-κB-related findings in these preclinical systems. The paper’s PubMed record identifies the models and formulation studied.

This 2020 work broadened the formulation context from doxorubicin and glioma models to irinotecan and a lung-cancer model. It did not establish that all CB5005-containing constructs behave alike. Peptide density, conjugation chemistry, drug cargo, particle properties, dose, tumor model, and administration conditions can each affect the observed outcome.

The 2022 CB5005N study concerns a derivative, not full CB5005

A 2022 Frontiers in Chemistry article studied a peptide designated CB5005N in a gambogic-acid liposome system using breast-cancer cells and mouse experiments. The article describes CB5005N as the nuclear-localization portion or derivative with the sequence VQRKRQKLMPC. That 11-residue peptide is not equivalent to the full 21-residue CB5005 sequence disclosed in the earlier patent. The full Frontiers article makes the construct distinction visible in the study’s formulation and methods.

The distinction is more than nomenclature. Removing the cell-permeable segment changes the molecule being tested, while attachment to a liposomal system introduces another delivery architecture. The 2022 results may inform research on the nuclear-localization-derived sequence, but they should not be reported as though they were a direct replication of experiments with full-length CB5005.

What the affiliations show—and what they do not

The documents establish a narrow continuity across the record. Yao-Zhong Lin appears as a co-inventor in the patent family and later as a co-author on the 2016, 2018, and 2020 CB5005-related papers. Those publication records include Celtek Bioscience among the listed affiliations.

This continuity connects an inventor named in the original legal disclosure with later peer-reviewed preclinical research. It does not, on its own, establish the current status of a Celtek development program, ownership of every later formulation, continuing patent enforceability, commercial availability, or regulatory authorization. It also does not turn co-authorship or affiliation into proof that the reported findings were independently replicated.

Historical SBIR records provide additional background rather than direct validation. They list Celtek Bioscience Phase I projects titled “Enhancement of Cancer Therapy by Inhibiting NF-kB” in 2003 and “Peptide Inhibitor For Alzheimer’s Disease Therapy” in 2004. These records indicate early research interests, but a Phase I SBIR award represents support for early-stage research. The Alzheimer’s-related project should not be folded into the later cancer-related CB5005 patent family without direct documentary evidence connecting them.

The strongest conclusion supported by the record

The CB5005 patent publication history documents a progression from invention disclosure to later experimental investigation. The 2004 provisional filing and subsequent patent family disclosed the peptide sequence, proposed uses, cell experiments, and legal claims. Issuance of U.S. Patent 7,408,022 in 2008 confirmed that claims were granted in the United States; it did not validate CB5005 as a treatment.

The papers published from 2016 through 2020 added peer-reviewed evidence involving cells, tumor spheroids, and mouse models, while the 2022 paper investigated a shorter derivative in another liposomal system. This is a meaningful preclinical literature trail, but it remains preclinical. The distinction between cultured cells, animal models, and human evidence is explained further in this guide to the biotechnology evidence ladder.

The defensible reading is therefore specific: CB5005 moved from a patent-defined peptide and inventor-reported experiments into several peer-reviewed formulation and delivery studies. The record supports continued scientific investigation across multiple preclinical systems. It does not establish human efficacy, human safety, regulatory approval, or present commercial and legal status. Keeping those boundaries visible is what turns a list of documents into an accurate research history.