Current Issue : October - December Volume : 2020 Issue Number : 4 Articles : 5 Articles
The discovery of numerous potent and broad neutralizing antibodies (bNAbs) against\nHuman Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein has invigorated the potential\nof using them as an effective preventative and therapeutic agent. The majority of the anti-HIV-1\nantibodies, currently under clinical investigation, are formulated singly for intra-venous (IV) infusion.\nHowever, due to the high degree of genetic variability in the case of HIV-1, a single broad neutralizing\nantibody will likely not be suffcient to protect against the broad range of viral isolates. To that end,\ndelivery of two or more co-formulated bnAbs against HIV-1 in a single subcutaneous (SC) injection\nis highly desired. We, therefore, co-formulated two anti-HIV bnAbs, 3BNC117-LS and 10-1074-LS,\nto a total concentration of 150 mg/mL for SC administration and analyzed them using a panel of\nanalytical techniques. Chromatographic based methods, such as RP-HPLC, CEX-HPLC, SEC-HPLC,\nwere developed to ensure separation and detection of each antibody in the co-formulated sample.\nIn addition, we used a panel of diverse pseudoviruses to detect the functionality of individual\nantibodies in the co-formulation. We also used these methods to test the stability of the co-formulated\nantibodies and believe that such an approach can support future efforts towards the formulation and\ncharacterization of multiple high-concentration antibodies for SC delivery....
Bradykinin (BK) and bradykinin-related peptides (BRPs), which were identified from\na diversity of amphibian skin secretions, exerted contractile and relaxing effects on non-vascular\nand vascular smooth muscle, respectively. Here, we report a novel bradykinin-related peptide\nwith a molecular mass of 1890.2 Da, RVAGPDKPARISGLSPLR, which was isolated and identified\nfrom Ordorrana hejiangensis skin secretions, followed by a C-terminal extension sequence VAPQIV.\nThe biosynthetic precursor-encoding cDNA was cloned by the â??shotgunâ? cloning method, and the\nnovel RR-18 was identified and structurally confirmed by high-performance liquid chromatography\n(HPLC) and tandem mass spectrometry (MS/MS). Subsequently, the myotropic activity of the\nsynthetic replicate of RR-18 was investigated on the rat bladder, uterus, tail artery and ileum\nsmooth muscle. The peptide was named RR-18 in accordance (R = N-terminal arginine,\nR = C-terminal arginine, 18 = number of residues). In this study, the synthetic replicates of RR-18\nshowed no agonist/antagonism of BK-induced rat bladder and uterus smooth muscle contraction.\nHowever, it displayed an antagonism of bradykinin-induced rat ileum contraction and arterial\nsmooth muscle relaxation. The EC50 values of BK for ileum and artery, were 214.7 nM and 18.3 nM,\nrespectively. When the tissue was pretreated with the novel peptide, RR-18, at the maximally effective\nconcentration of bradykinin (1 x 10-6 M), bradykinin-induced contraction of the ileum and relaxation\nof the arterial smooth muscle was reduced by 50â??60% and 30â??40%, respectively. In conclusion, RR-18\nrepresents novel bradykinin antagonising peptide from amphibian skin secretions. It may provide\nnew insight into possible treatment options for chronic pain and chronic inflammation....
Biologic drugs represent a large and growing portion of health expenditures. Increasing\nthe use of biosimilars is a promising option for controlling spending growth in pharmaceutical care.\nAmid the considerable uncertainty concerning physiciansâ?? decision to prescribe biosimilars, explicit\ncost control measures may help increase biosimilar use. We analyze the role of regional cost control\nmeasures for biosimilars and their association with physician prescriptions in ambulatory care in\nGermany. We collect data on cost control measures implemented by German physician associations and\nnational claims data on statutory health insurance covering 2009 to 2015. We perform panel regressions\nthat include time and physician fixed effects to identify the average associations between cost control\nmeasures and biosimilar share/use while controlling for unobserved physician heterogeneity, patient\nstructure, and socioeconomic factors. We identify 44 measures (priority prescribing, biosimilar quota)\nfor erythropoiesis-stimulating substances, filgrastim, and somatropin. Estimates of cost control\nmeasures and their consequences for biosimilar share and use are heterogeneous by drug, measure\ntype, and physician group. Across specialists, biosimilar quotas accounted for 5.13% to 9.75% of the\ntotal average biosimilar share of erythropoiesis-stimulating substances. Explicit quota regulations are\nmore effective than priority prescribing. Regional variation in biosimilar use can be partly attributed\nto the presence of cost control measures....
Antibody drug conjugates (ADCs), consisting of a cancer-specific antibody and cytotoxic\npayload, are shown to be a potent class of anticancer therapeutics, with enhanced therapeutic effcacy\nand reduced â??off-targetâ? side effects. However, the therapeutic window of ADCs is narrowed by\nproblems such as diffculty in site-specific conjugation of payload, changes in antibody stability\ndue to payload conjugation, and diffculty in tissue penetration. In this respect, aptamers have\nadvantages in drug-delivery, as they can be easily and stably conjugated with cytotoxic drugs. We\npreviously reported that oligobody, an aptamer-antibody complex, is a novel delivery method for\naptamer-based therapeutics. In the current study, we describe DOligobody, a drug-conjugated\noligobody comprising an aptamer-drug conjugate and an antibody. A cotinine-conjugated anti-HER2\naptamer (cot-HER2apt) was specifically bound to HER2-positive NCI-N87 cells, and underwent\nreceptor-mediated endocytosis. Further, HER2-DOligobody, a cot-HER2apt-conjugated monomethyl\nauristatin E (cot-HER2apt-MMAE) oligobody, inhibited the growth of HER2-positive NCI-N87 cells.\nFinally, systemic administration of HER2-DOligobody significantly reduced tumor growth in a\nxenograft mouse model. Taken together, these results suggest that our DOligobody strategy may be a\npowerful platform for rapid, low-cost and effective cancer therapy....
There is increasing data in favour of follicle-stimulating hormone (FSH) therapy in patients\nwith oligo-asthenozoospermia and normal-range gonadotropins in order to increase sperm count\nand above all sperm motility. Some studies showed an improvement in DNA fragmentation and\nspontaneous pregnancy. Recently, biosimilar FSH has been marketed with the same indications. We\nperformed a retrospective multicentric case-control study involving 147 asthenozoospermic patients\nbetween 18 and 45 years of age. A total of 97 patients were treated with biosimilar FSH 150 UI three\ntimes a week for 3 months, while 50 control subjects received no treatment. Patients were evaluated\nat baseline and after 3 months with semen analysis including DNA fragmentation, testicular colour\nDoppler ultrasound, and blood tests. Spontaneous pregnancies were recorded during a further\nfollow-up period of 6 months. Treated patients showed after treatment a statistically significant\nincrease in sperm concentration, total sperm count, and total motile sperm, as well as improved\nprogressive motility and non-progressive motility. DNAfragmentation showed a significant reduction.\nConversely, in the control group, no significant change was found. Pregnancy rate was significantly\nhigher in treated patients. These data suggest comparable effcacy of biosimilar FSH in the treatment\nof male infertility; however, larger studies are needed to confirm our results....
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