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Cl3hmAb

A Neutralizing Antibody Against Multiple HIV Strains

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Drug Name Cl3hmAb
Description Clone 3 human monoclonal antibody (Cl3hmAb) binds to KLIC, an immutable site of the transmembrane protein gp41 on the HIV (human immunodeficiency virus). Compared with other epitopes developed for antibodies directed against HIV, KLIC  occurs with greater frequency and is more conserved. As a result, Cl3hmAb is a broadly neutralizing antibody against HIV without “virus escape” and can become a new immunotherapy method to treat HIV.
Compared to the best of currently known 90 mAbs, Cl3hmAb has demonstrated superior neutralizing capability. Tested against 43 strains of the virus in 5 independent research institutes worldwide, 95% of the HIV viruses were neutralized at an IC 90 or above, with impressively 2.6 times better neutralization potency than that of the currently best-known antibodies.
Target Glycoprotein gp41 (the subunit of envelope glycoprotein gp160)
Drug Modality Humanized monoclonal antibody
Indication Acquired immune deficiency syndrome (AIDS)
Product Category Anti-HIV agent
Mechanism of Action Cl3mAb prevents HIV from infecting host cells by binding to gp41.
Status Preclinical
Patent Patent covers the recombinant form of the Clone 3 antibody, related commercial applications to treat HIV, and cell line that produces Cl3hmAb.

Collaboration Opportunity

Protheragen Inc. is actively seeking partnership for our business partner to further develop Cl3hmAb. Potential collaboration can be strategic alliance, licensing, or marketing agreement.

We look forward to hearing from you.

Envelope Glycoprotein gp160 (the Precursor of Glycoprotein gp41)

Introduction Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. Then gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.
Gene description Envelope surface glycoprotein gp160, precursor
Official Symbol env
Gene Type Protein coding
Organism Human immunodeficiency virus 1 (gb-acronym: HIV-1)
Lineage Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae; Lentivirus; Primate lentivirus group
mRNA Refseq  
Protein Refseq NP_057856; NP_579893; NP_579894; NP_579895
UniProt ID P04578
Function Envelope glycoprotein gp160 is a homotrimer encoded by a viral gene Env and is cleaved into gp41 and gp120. Exposed on the surface of the viral envelope, the glycoprotein gp120 binds to the CD4 receptor and chemokine co-receptors on host cells, particularly the helper T-cell. The glycoprotein gp41 is non-covalently bound to gp120, and participates in the second step by which HIV enters the host cells.
Major Conditions Acquired Immune Deficiency Syndrome (AIDS)

Acquired Immune Deficiency Syndrome (AIDS)

HIV is a retrovirus belonging to the Retroviridae family, lentivirus genus, which was first identified in 1983. There are two main forms of the virus that cause human disease: HIV-1 and HIV-2. Athough their DNA sequences differ by as much as 40%, the two forms are similar in their genetic structures and modes of transmission. Compared with HIV-1, HIV-2 is considered less virulent, progressing to AIDS less frequently and associated with lower mortality.

HIV causes AIDS, a gradual deterioration of the immune system, leading to opportunistic infections and ultimately, death. The Joint United Nations Programme on HIV and AIDS (UNAIDS) estimated that there were approximately 37.9 million adults and children living with HIV/AIDS worldwide in 2018, with 79% were aware of their status and 62% accessing antiretroviral drug therapy. In 2018, a total of 770,000 (range 570,000 to 1.1 million) people died of AIDS-related causes worldwide. USD 26.2 billion (constant 2016 dollars) will be required for the global AIDS response in 2020.

With the adoption and widespread use of highly active antiretroviral therapy (HAART), AIDS-related mortality has decreased significantly in the developed world. Nonetheless, side effects, compliance issues, and cost of the HAART all contribute to the limitation of this therapy to completely eradicate the HIV virus. The strategies to boost the host immune response in AIDS patients, such as Chimeric Antigen Receptor T Cell therapy and vaccine therapy may prove more promising. Immunotherapeutic agents may be used as adjuncts to HAART and potentially as HAART-sparing treatments.

Cl3mAb Prevents HIV from Infecting Host Cells by Binding to gp41.

The specific binding between the virus envelope protein and the two receptor sites on the CD4 cells causes the HIV to be infectious:
(1) The glycoprotein gp120 first binds to CD4 receptor, followed by the binding with the chemokine co-receptors CXCR4 and/or CCR5.
(2) Conformational changes of the glycoprotein gp41 lead to the fusion of CD4 cell membrane and viral envelope.

As a broadly neutralizing antibody, Cl3hmAb prevents the infection caused by multiple HIV strains by abrogating an essential infectivity process which requires the fusion between the viral membrane and the CD4 cell membrane. KLIC, to which Cl3hmAb binds, is the essential core epitope of the virus surface transmembrane protein gp41 and has a linear conformation. KLIC is composed of a few amino acids, and the targeted sequence of the amino acids are highly conserved. Thus, compared with other epitopes developed for neutralizing monoclonal antibodies directed against HIV, KLIC occurs with greater frequency and more conserved.

Figure 1. from Tagliamonte et al. Journal of Translational Medicine 2010, 9(Suppl 1): S1

Patent Status of Cl3hmAb

Patent covers the recombinant form of the Clone 3 antibody, related commercial applications to treat HIV, and the cell line that produces Cl3hmAb.


The Neutralizing Effect of Clone 3 Antibody

Tests in five international research institutes demonstrated that Clone 3 antibody neutralizes 41 of 43 (95%) primary HIV isolates tested.

Tests were conducted on Clades A, B, C, E, and F found worldwide.

Diane Hong Business Development Manager
1-516-927-7606
info@protheragen.com

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