Background & AimHarnessing the specificity and versatility of antibodies for cell and gene therapies as a delivery vehicle offers a transformative advance for precision medicines. From their ability for targeted delivery of therapeutic payloads to modulation of cellular interactions, antibodies hold immense potential in refining the precision, efficacy, and safety of future therapies. However, finding the right antibody candidate can be laborious and inefficient.Methods, Results & ConclusionHerein, we introduce an advanced and comprehensive solution to quickly identify and produce antibody leads for cell and gene therapy. This method involves the use of next-generation sequencing of outputs derived from both in vivo (i.e., B-cells and PBMCs) and in vitro (i.e., phage display) discovery campaigns. We pair this with an advanced bioinformatics platform that leverages machine learning to optimize the selection of potential antibody candidates. With this approach, it uncovered 5 – 50x more of the population diversity compared to traditional methods (e.g., random colony screening with Sanger). While next-generation sequencing expands the coverage of the underlying sequence diversity, top candidates are prioritizes using machine learning, selecting diverse leads from distinct clusters and prioritizing leads within clusters that have a reduced number of sequence-based liabilities. Once candidates are selected, they can be efficiently produced because we optimized expression vectors for high production rates. Thus, resulting in a quick and effective solution to generate candidates for vehicles in cell and gene therapy.In summary, we present our advanced end-to-end solution that uses next-generation sequencing, machine learning-based lead prioritization, and optimized antibody expression. Taken together, this platform consistently elevates the number of diverse leads and helps to uncover rare clones with favorable biophysical properties.

Storage studies of almond milk powder mix of standard formulation comprising skimmed milk powder, cane sugar, starch, almond, cardamom and permitted food colour were conducted in 4 types of packages, viz., pouches made of polypropylene, polyester/polyethylene, metallized polyester/polyethylene and high-density polyethylene (H D PE) rigid containers. The storage conditions were 38degreesC with 92% RH and 27degreesC with 65% RH. The chemical, microbiological and sensory qualities of the product, initially and at regular intervals were assessed. The shelf-life of the mix was 20, 30, 65 and 90 days in polyester/polyethylene, polypropylene, metallised polyester/polyethylene and HDPE packaging materials, respectively at 38degreesC and 92% RH and could be stored for more than 6 months at 27degreesC and 65% RH in all the packages studied.

A multicentre, randomized, comparative clinical trial of 200 mg RU486 (Mifepristone) followed 48 h later by either 5 mg 9-methylene PGE(2) vaginal gel (meteneprost) or 600 mug oral PGE(1) (misoprostol) for termination of pregnancy within 28 days of the missed period, was carried out through the Indian Council of Medical Research's (ICMR) network of Human Reproduction Research Centres (HRRCs). A total of 893 subjects were assessed regarding their therapeutic responses to the two different treatment groups. The results indicated a success rate of 84.6% among 453 women treated with RU486 followed by 9 methylene PGE(2) vaginal gel, that was not significantly different from the success rate of 87.7% observed in 440 women treated with RU486 followed by oral PGE(1). The majority of study subjects (90%) started bleeding within 72 h. About 26% of the subjects had started bleeding before the administration of any prostaglandin. The average duration of bleeding in all the subjects was about 7 days. No life threatening side effects were observed among the subjects in two treatment groups. Gastro-intestinal complaints were reported more often by women treated with oral PGE(1) as compared to those treated with 9-methylene vaginal PGE(2) gel; nausea occurred in 25.7% and 19.2%, vomiting in 6.8% and 4.6%, and diarrhoea in 4.8% and 0.9% of the subjects in the 2 treatment groups, respectively. Fever higher than 38 degreesC and severe abdominal pain were reported by 4.2% and 5.0% of all subjects treated, respectively. Intravenous infusion of glucose and saline was required by 6 subjects in each treatment of the prostaglandin treated groups. Blood transfusion was required in 2 subjects, one in each treatment group, for profuse bleeding. (C) 2000 Elsevier Science Inc. All rights reserved.

A total of 627 women who had discontinued the use of the Norplant-II implants for various reasons and were exposed to the risk of pregnancy were followed-up for two years for return of fertility. The cumulative conception rates in women who had discontinued due to planning pregnancy were 80.3 per 100 women at one year and 88.3 per 100 women at two years. The majority of women who did conceive (90 percent), had fall-term normal live births; about 4 percent of women had spontaneous abortions, the remaining 6 percent decided on elective termination of pregnancy (ETP). The cumulative conception rates in women who discontinued due to bleeding irregularities and 'other reasons' were 64.5 and 55.8 per 100 women at one year and 77.9 and 75.1 per 100 women at two years, respectively. These rates were significantly lower as compared to those observed in women who discontinued due to planning pregnancy. A large proportion, about 40 percent, of women who conceived after discontinuation of the method due to bleeding irregularities and ''other reasons,'' opted for ETP indicating that many women in these two groups,did not desire another child and that such women need to be counselled for adopting another method of contraception. The spontaneous abortion rates observed in ex-users of Norplant-II implants (1.7 to 4.4% pregnancies) were comparable to the spontaneous abortion rates prior to Norplant-II implant use (3.6% pregnancies) indicating that ex-users of Norplant-II implants were not at a higher risk of spontaneous abortion. There was no association between the pregnancy rates and either duration of Norplant-II implants use or bleeding patterns during the three months prior to discontinuation of the method in this sample. However, there was a delay in return of fertility in women aged more than 30 years as compared to those who were below the age of 30 years. The study indicates that the return of fertility was not impaired in ex-Norplant-II implant users who were planning pregnancy. In addition, those women who continued with the pregnancy until term delivered full-term normal babies in all the study groups.

A dose-finding study was carried out with two different doses of RU 486 (200mg or 600mg) each in combination with two doses of 9-methylene-PGE2 gel (3mg or 5mg) for termination of pregnancy between 7 to 28 days after missed menstrual period. It was observed that the success rates with 200mg RU 486 followed by 5mg 9-methylene-PGE2 gel were 94.5% and 89.6% in women with 7-14 days and 15-28 days of missed menstrual period, respectively. These rates were similar to those observed with 600mg RU 486 given along with 3mg or 5mg 9-methylene-PGE2 gel and were significantly higher than those observed with 200mg RU 486 given along with 3mg 9-methylene-PGE2 gel. All subjects except four started bleeding following the treatment. The average duration of bleeding in subjects with successful outcome (complete abortion) ranged between 7.0 to 11.8 days in the four different treatment schedules. There were no serious side effects with any of the treatment schedules; only one subject required transfusion of one unit of blood for heavy bleeding. The immediate and delayed complication rates were similar with the four treatment schedules.

The subdermal implant NORPLANT II contraceptive was studied for its safety, efficacy and acceptability over a period of 5 years of use in a phase III multicentre clinical trial. A total of 1,466 women were observed for 52,849 women-months of use. Only four pregnancies were reported during the study period, giving a method failure rate of 0.8 per 100 users at 5 years of use. The continuation rates were 61.4, 49.0 and 42.1 per 100 users at 3, 4 and 5 years of use, respectively. The majority of the discontinuations were due to bleeding irregularities which accounted for 22.2 26.3 and 28.5 per 100 users at 3, 4 and 5 years of use, respectively. The next common reason was planning pregnancy which was observed mainly in women having one child. The discontinuations due to infection, expulsion or displacement of device were very low (0.2-0.3 per 100 users). Due to vigorous efforts made by the centers to follow the subjects, the lost-to-follow-up rate was very low (1.6% at 5 yr).