Paradigm shift in Discovery & Secretion of Biosimilars via path breaking Innovation

Radha108 nano peptides stimulate the Cytotoxic T-cells of the innate immune system to naturally produce bio similars like cytokines (interleukins and interferons). Radha108 is proven to increase the production of these cytokines by 5 folds. These nano peptides get absorbed in the blood through buccal mucosa and have potential of crossing the blood brain barrier (BBB). Radha108 acts on pituitary gland that in turn promotes the differentiation of B cells, maturation of macrophages, monocytes and stimulates the production of cytokines IL-1 to IL-11, TNF-α, INF–γ. It also helps in the maturation of immature thymocytes either into helper or suppressor T cells that help in priming body’s immune system against infections and immune disorders like asthma, allergy, upper respiratory tract infection (URTI), carcinomas and type 2 diabetes thereby saving huge amount of resources and money that are spent in treating such ailments with little or no efficacy. Radha108 acts as a molecular signaling device which works through receptors on target cell surfaces. These nano-informational peptide proteins mitigate cell fusion by docking on the glycoprotein receptors present on the CD4+ and CD8+ T cells for Gp120, Gp180 and Gp160 thereby closing the entry of virus, foreign antigen and allergens. Radha 108 nano peptides SEQ ID 1-8 was extracted from bovine colostrum and has been granted the US patent (U.S. Patent No. 9,249,188 & 8,518,454 B2). These nano peptides consist of ELVPGVPRGTQL (DNAbinding Protein Inhibitor ID -3), VAIIQHMIKKLR (Epstein – Barr virus induced gene-2), LPQEVLNENLLRF (Alpha S1Casein), RLNARMAELR ( S-adenosylm ethionine synthetase isoform type -1), SSLQVLNMSHN( Tolllike receptor -4), EYQELMNVK (Keratin type II cytoskeletal 59kDa component IV), VDTLNDEINFLR (Keratin type II cytoskeletal 7), DGIVNENLAER ( Ribonucleoside – diphosphate reductase small chain). Thus, Radha 108 nanopeptides stimulate the secretion of biosimilars (wide range of cytokines like interleukins and interferons) that are very effective in treating viral infections like HIV, cold, swine flu and immune disorders like allergy, asthma, arthritis, diarrhea, fatiguemalaise, anaemia, endometriosis by stimulating the cytotoxic T cells

frequent international travel, diseases now spread more easily than ever before. Fortunately, recent research has uncovered a natural agent, which can increase our ability to fight disease and improve the quality of life for many people.
Radha 108 nano peptides extracted from mammalian colostrum (first milk) stimulates our body's own immune system as a broadspectrum anti-viral and a new generation immunomodulator to fight against several diseases and prevents all communicable infections. It is a natural product manufactured by nano-biotechnology patented proprietary ultra-nano filtration processes from bovine colostrum.
Radha 108 consists of low molecular weight active pharmaceutical ingredients (API) -Proline Rich Polypeptides (PRPs). Radha 108 is registered under Ayush license number GA/1647 (Validity, 2018). Radha-108 belongs to a class of nano informational peptides, consisting of an oligo ribonucleotide attached to a peptide molecule. It acts as a broad spectrum immuno-modulator and antiviral agent via increasing body's own immune system naturally.
The innovation of Radha 108 in the field of immunotherapy is quiet revolutionary in therapeutic and preventive medicine. It is a form of treatment that uses different aspects of the immune system, its cells and molecules, and its various stratagems to tip the balance in favour as our body battles to maintain a healthy state.
Almost all individuals, healthy or diseased, with a few exceptions have benefited from regular Radha 108 supplementation. The use of Radha 108 did not cause any side effects even when given in high doses, exceeding the normal doses for prolonged periods. It has been shown to be beneficial in people with specific ailments as well.
Numerous studies have shown the effectiveness of Radha 108 in eliminating or alleviating symptoms of herpes, chronic fatigue syndrome, and viral infections including Epstein Barr, hepatitis, secondary infections due to AIDS, Candida, cancer and many other diseases and infections. Studies have also shown that continued use provides the greatest benefit, with maximum immune activity occurring 24 to 48 hours after taking the first dose.
The need for Radha 108 for better health stems from the growing awareness that prevention is the best cure. With the increasing risks of antibiotic resistance and significant health threats, such as severe acute respiratory syndrome (SARS), the medical community increasingly turns to the inherent concept of immunization using vaccinations.
Radha 108 is a kin to a vaccine but rather than exposing the patient's immune system to the actual disease or a deactivated version of the same, Radha 108 exposes the patient's immune system to the memory of a health threat, whether foreign or native, and the knowledge of how to best respond to protect itself. In view of proven global safety and efficacy, the product is now ready for a global launch with the product having been patented in several countries like the United States, Africa, Canada and Asia (Singapore and India).

The background of the invention
• Colostrum is the pre-milk substance produced from the mother's breast of all mammals during the first 24 hours of lactation, typically the first 3 milks.
• Colostrum has been known as an immune booster since time immemorial. Colostrum triggers at least 50 processes in the newborn, including transferring all immune factors and the entire immune defense memory from the mother's own immune system.
• Bovine colostrum is up to 40 times richer than human colostrum in immune factors including nano informational peptides, PRPs, immunoglobulins, cytokines, interferons, lactoferrin, and transfer factor.
• They are produced by T-lymphocytes and can transfer the ability to recognize a pathogen to native cells. However, no one till date has been able to isolate active ingredients especially nano informational low molecular weight nano peptides and formulate a product that has the same effect as that of the mother's first three milks, after the birth of the child.
• It has been indicated that colostrum stimulates the lymphoid tissue providing benefits in aged or immune deficient people ( Bocci, Bremen, Corradeschi, Luzzi and Paulesu in Journal Biology).
• In addition, researchers reported that colostrum stimulates maturation of B lymphocytes (type of white blood cell) and primes them for the production of antibodies, enhances growth and the differentiation of white blood cells. Similar activity in cow and human colostrum can also activate macrophages (Dr. M. Julius, McGill University, Montreal: Science News).
• Furthermore, it was indicated that bovine colostrum contains high levels of growth factors that promote normal cell growth and DNA synthesis (Oda, Shinnichi et. al).
• Besides, it has been suggested that an important role for growth factors is in promoting wound healing. Accelerated healing is important in treatment of trauma and surgical wounds (Bhora et. al).
• As such, colostrum contains hundreds of small peptides which serve numerous purposes. Studies have documented the presence of a number of bioactive peptides but no mention has been made of the use of these peptide fragments, their specific sequence or information regarding their isolation.
• Therefore, their segregation and isolation will facilitate gathering of further information with regard to their individual function and help formulate specific and targeted therapies for numerous diseases that are cured by colostrum.
• The challenge with this task is that the peptides are extremely sensitive to temperature, pH, stress, and shear factors. This poses several difficulties in their isolation and in preserving their biological activity and in the method of collection of colostrum so as to be able to deliver it to the patient while retaining its full biological activity. • The present invention addresses these shortcomings by providing isolated nano peptides from colostrum, establishing their method of isolation and the therapeutic uses of the isolated nano peptide fragments. With reference to this innovation, the US patent for this product, US 20070212367 is notable: • US 20070212367-This patent application discloses an immunologically active PRP isolated from mammalian colostrum fluids for treatment of viral and non-viral diseases, a method and a system for processing mammalian colostrum fluids and a pharmaceutical formulation.

Mode of action:
• The informational proteins, Radha 108 are active in mitigating cell fusion.
• Radha 108 series docks on glycoprotein receptor on the cell surface and thus restricts viral entry into the immune cells.
• Radha 108 series get absorbed in the blood stream through buccal mucosa and crosses the BBB.
• The levels of interleukins and cytokines are increased substantially.
• It supports the regulation of the thymus by producing functionally active natural killer (NK) cells.
• Radha 108 augments cell-mediated immunity and activates T-cell precursors to produce helper and suppresser T-cells increasing CD4/8 counts.
• Radha 108 promotes growth and differentiation of stem cells in response to any disease.
Fusion of human immunodeficiency virus (HIV) particles with human white blood cells, particularly CD4 cells occurs with the aid of glycoprotein (Gp) epitopes on the viral wall. Radha108 docks on HIV Gp120 mimicking receptor on the cell surface and thus restricting virus/antigen entry into the immune cells.
Radha 108 proteins directly support the NK cells of the immune system. NK cells provide the front line of defense specially equipped to locate and kill disease cells. NK cells attach to the surfaces of foreign substances or their outer cell wall, and inject a chemical "grenade" (granule) into the interior. Once inside, the granules explode and destroy the foreign invader within five minutes.
The NK cell itself remains intact and moves on to destroy the next immune attacker. Many doctors and clinicians are finding Radha 108 helpful in promoting NK function and activity as well as supporting a healthy immune system for all patients.
The immune system plays a great role in the quality of our health. Strong, active and optimally functioning NK cells promote optimal health and deter foreign substances from affecting immune function.
• Radha108 (PRP) promotes differentiation of B cells, differentiation and maturation of macrophages and monocytes.
• Activates NK cells, cytotoxic cells of the innate immune system.
• Mitigates cell fusion and docks on HIV glycoprotein like Gp120, 180, 160 and 41 mimicking receptor on the cell surface closing entry of viruses.
• Stimulates the maturation of immature thymocytes into either helper or suppressor T cells.
• Radha108 also functions as a molecular signaling device which works through receptors on target cell surfaces. These proteins also mediate interactions between cells directly and regulate processes taking place in the extracellular environment. The cytokines interleukin 1 and 6, interferon-gamma and lymphokines have been shown to stimulate the lymph glands and are thought to be highly effective antiviral immune substances.
Interleukins regulate the duration and intensity of the immune response and are responsible for cell to cell communication, boost T-cell activity and the production of immunoglobulins.
The cytokine IFN-beta is involved in the regulation of unspecific humoral immune responses and immune responses against viral infections.
Extensive preclinical studies have documented a direct cytostatic and cytotoxic effect of the cytokine TNF-alpha against subcutaneous human xenografts and lymph node metastases in mice as well as a variety of immunomodulatory effects on various immune effector cells, including neutrophils, macrophages, and T-cells.
Following is a description of some of the biological activities of the IFN-beta and TNF-alpha cytokines: It is a glycoprotein with 20,000MW consisting of 166 amino acids. It is also known as fibroblast interferon, Type-1 interferon, pH2stable interferon, and R1-GI factor. IFN-beta is produced mainly by fibroblasts and some epithelial cell types.
IFN-beta is involved in the regulation of unspecific humoral immune responses and immune responses against viral infections. IFN-beta increases the expression of HLA class I antigens and blocks the expression of HLA class II antigens stimulated by IFN-gamma. IFN-beta stimulates the activity of NK-cells thereby activating antibody-dependent cytotoxicity.
The activity of T suppressor cells is also stimulated by IFN-beta. IFN-beta enhances the synthesis of the low affinity IgE receptor CD23. In activated monocytes, IFN-beta induces the synthesis of neopterin.
It also enhances serum concentrations of beta-2-microglobulin. IFN-beta selectively inhibits the expression of some mitochondrial genes. IFN-beta shows anti proliferative activity against a number of cell lines established from solid tumors.
IFN-beta can be used for topic treatment of condylomata acuminata. It is also suitable for the prophylactic use following surgical removal of large condylomas. Some studies suggest that IFN-beta tends to prevent disease activity in patients with multiple sclerosis.
IFN-beta has been used in the treatment of chronic active hepatitis B and appears to be most promising if the disease has not lasted longer than 5 years. The antiviral activity of IFN-beta is demonstrated also in the treatment of severe childhood viral encephalitis.
IFN-beta is a lipophilic molecule that should be particularly useful for local tumor therapy due to its specific pharmacokinetics.
It is hardly removed from the tumor tissues after intraregional administration and hence also shows little systemic side effects. Head and neck squamous carcinomas, mammary and cervical carcinomas, and also malignant melanomas respond well to treatment with IFN-beta.
IFN-beta also appears to be very promising for the adjuvant therapy of malignant melanomas with a high potential for metastasis. Response rates have been reported to be improved by combining IFN-beta with antineoplastic agents or other cytokines.
In many instances a combination of the various interferons has been found to cause synergistic effects. The antiviral/anti proliferative/antitumor properties of IFN-beta are potentiated by febrile temperatures. 84 TNF-alpha is a glycoprotein with a 17,000MW consisting of 157 amino acids. It has immuno-modulating effects on various immune effector cells. TNF-alpha shows a wide spectrum of biological activities.
It causes cytolysis and cytostasis of many tumor cell lines in vitro. Sensitive cells die within hours after exposure to picomolar concentrations of the factor and this involves, at least in part, mitochondria-derived second messenger molecules serving as common mediators of TNF cytotoxic and gene-regulatory signaling pathways.
The factor induces hemorrhagic necrosis of transplanted tumors. Within hours after injection TNF-alpha leads to the destruction of small blood vessels within malignant tumors. The factor also enhances phagocytosis and cytotoxicity in neutrophilic granulocytes and also modulates the expression of many other proteins. Radha 108 promotes the production of these cytokines (IFN beta and TNF-alpha). The trial was conducted to evaluate the safety of Radha 108 Oral Spray on 12 HIV patients for a period of 30 days.
• No adverse effects were reported during the study.
• Improvement was observed in HIV associated clinical symptoms (Table 1).
• Week after week weight gain showed a positive response. • Radha 108 Oral Spray appeared to be safe and well tolerated.
• Significant viral load reduction in minimizing the infection associated with HIV/AIDS.
• Week after week weight gain showed a positive response.
• Marked reduction in symptoms.
• Significant increase in CD4 count.

Phase III study: Rwanda, Africa
A t-Trial was conducted in 60 patients with HIV/AIDS, where patients received a 12 month treatment with Radha 108 Oral Spray with an objective to study the efficacy and safety under clinical conditions.
• Patients were unaware of positive potentials of drug so as to avoid any bias.
• After day 1 moderate level of relief of diarrhea and fever was observed.
• Week after week weight gain showed a positive response.
• After 14 days, relief from skin lesion, mouth thrush, fever, diarrhea, tuberculosis symptoms was seen.
• After 90 days relief of all symptoms with increase in absolute CD4 counts and reduction in viral load.
• No adverse effects observed over 12 months follow up even after 5 years of therapy, and an improvement in Quality of Life was noted. 85 Nausea, Cough.

Phase III revalidation trial in
• Inclusion criteria was absolute CD4 cell count greater than 100 cells/mm3 and exclusion criteria was no pre-exposure to ART.      Absolute CD4 Count: Absolute CD4 cell count was available for all 50 patients with pre and post treatment values. There was an increase in Absolute CD4 count in 26 (52%) patients. Absolute CD4 cell count range with number of patients at baseline and at the end of study is shown in Figure  5. The inclusion criteria was absolute CD4 cell count greater than 100 cells/mm3and 100% symptomatic patients at baseline and exclusion criteria was no pre-exposure to ART.   88 100 % of the total study cases had vomiting at baseline and all the patients had relief from vomiting after treatment from 3rd Week onwards. (Figure 8) 100 % of the total study cases had fever at baseline and all the patients had relief from fever from 3rd week onwards. (Figure 9)  Absolute CD4 and CD8 cell count: • CD4 cell counts were available for all 51 patients with pre and post treatment values. There was an absolute increase in CD4 counts for 67% patients and an average increase in CD4 count by 27 (The median CD4 cell counts increased from 276 to 305). This effect was found statistically significant (p < 0.05). CD4 cell counts range with number of patients at baseline and at the end of study is shown in figure 12a.
• While there was a significant improvement in CD8 count with 75% of patients showing an increase in CD8 counts and the average difference in CD8 count from baseline to the week-12 was found to be 102.69 ± 267.44. This effect was statistically significant (p < 0.05). (Figure 12b)