• PleasegiveRespondtoEACHSTUDENT answer (below).Make sure yourRespondis atleast 100 wordsin length withnew informationandwritten in your own wordsandproviding thoughtful commentary/information/explanation.
• Provide aCuriosity Questionswith your respond.
• ProvideReferencesto support your feedback/comments/respond.

Student 1:

Curia is a research and development as well as manufacturing biotech company. They classify new chemical structures and develop drug leads. They are involved in research and development as well as manufacturing. The company manufactures steroids, hormones, highly potent compounds, gene synthesis, PCR cloning, mutagenesis, plasmid design , plasmid DNA scale- up, DNA sequencing, and custom APIs (Curia, n.d.). Of the drugs in development that I was able to get access to Mabs for Malaria and Coronavirus disease 2019 vaccine are in the inactive development stage (GlobalData, n.d.). The process for manufacturing the MAbs would be determining which antibody to use, then choosing a cell line to produce the antibody, next would be growing the cell line in a bioreactor with parameters ie. temperature, pH, dissolved oxygen and nutrient concentration to control the growth. Antibody production proceeds they are then harvested and purified. Once purified it is then prepared into final dosage ( Avantor, n.d.).

According the Curia, n.d., there has been over 600 patents that have been issued. Over past approximately 20 years the patent trend has fluctuated, having peaks in 2008 and 2012. The lowest it has been since the inception of the company was in 2019. The latest patent was published on December5, 2023 titled Choline salt forms of an HIV capsid inhibitor (GlobalData, n.d.). This company has over 350 drug discovery programs, 600 plus issued patents and approximately 95 preclinical and clinical candidates developed (Curia, n.d.) I would advise the company to manufacture in-house. Their stats prove that the company can handle producing products that are currently in development. Cruia is a contract research, development, and manufacturing organization (CDMO) (Cruia, n.d.), having the appropriate capable staff to handle in-house production.

Student 2:

Legend Biotech is a biotechnology company that seeking to leverage cell therapies to treat cancers in patients. By leveraging stem cells and various intracellular machinary, Legend Biotech is hoping to treat common cancer types. Legend Biotech currently is producing Carvykti, a gene therapy that manipulates white blood cells of patients to attack their multiple myeloma cancer cells (MEDICATION GUIDE CARVYKTI (Ciltacabtagene Autoleucel), 2023). This company is also working on several other variations of cancer treatments (3 according to their website) aiming to use several immune cells such as CAR- T, CAR-NK,and non-genetically modified CAR-T cells to attack cancer cells (Legend Biotech, n.d.). According to a review paper, Carvykti and other CAR T cell products are produced via various cellular growth by growing T cells and then inoculating these cultures with antibody-coated beads or plate-bound antibodies to induce T cell activation and then are genetically modified using delivery methods such as lentiviral vectors (Watanabe et al., 2022). These products are not grown at mass-scale like other cellular products mentioned in class as they are specifically catered towards individual patients (thereby only a specific amount is grown by traditional laboratory means on plates).

This company, despite not having an enormous variety of specifically marketed products, does indeed have its own IP. Legend Biotech owns the patent for 'BCMA-Targeted CAR-T Cell Therapy for Multiple Myeloma', a treatment for a subject who has multiple myeloma with a single infusion of chimeric antigen receptor (CAR)-T cells that comprise an anti-BCMA CAR administration (Schecter & Fan, 2022). The company also has several PCT applications, some of which have become US patents such as the similar patent which includes patented single-domain antibodies that target BCMA, and chimeric antigen receptors that comprise one or more anti-BCMA single-domain antibodies (Fan et al., 2021) In a theoretical scenario in which I am a consultant for this company, this research suggests to myself that this company should develop its products in-house. The amount of very specific engineering that needs to go on for these therapies (often genetically modifying cells for per-patient) does not lend itself well to enlisting the services of a CMO. Using them to create a specific patient therapy wouldn't somehow make the treatment development more streamlined like it would other biomanufacturing companies.

Student 3:

Atara Biotherapeutics is an allogeneic T-cell immunotherapy company dedicated to "harnessing the natural biology of T cells" (Atara Biotherapeutics, 2024). Atara Bio has 4 products; Tabelecleucel (tab-cel), ATA3219, ATA3431, and ATA188. All four pipelines were developed to treat cancer and/or autoimmune diseases using CAR T cell therapies. Tab-cel is the only approved by the European Union, and ATA3219, ATA3431, and ATA188 are still under development (Atara Biotherapeutics, 2024). To manufacture CAR T cells, Atara Bio could be using a automated stirred-tank bioreactor. Using this bioreactor has been proven to provide better overall cell yields compared to using a static T-flask culture, and is proven comparable to other expansion systems (Costariol et al., 2020). It even allowed T cells to retain expression of the CAR gene and retain their cytolytic function, even when the bioreactor is at the highest agitation intensity (Costariol et al., 2020).

Atara Bio has four patents that were granted to them and Amgen Inc. One of those patents is titled "Variant activin receptor polypeptides and uses thereof" (Sun et al., 2007). This invention "provides variant activin IIB soluble receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11" and provides "polynucleotides, vectors and host cells capable of producing the variant polypeptides and proteins" (Sun et al., 2007).

If I was a consultant for Atara Bios for there ATA3431 product, " an allogeneic dual CAR T candidate targeting both CD19 and CD20 antigens for autoimmune disease" (Atara Biotherapeutics, 2024), I would say that the company should use a CMO to manufacture this product. It will allow the company to hire experienced staff, that has gained knowledge from all of their different clients over time, and who has regulatory and quality knowledge for manufacturing. CMOs are also more cost effective compared to in house manufacturing since it costs a lot to individually train the staff and purchase the equipment required to manufacture CAR T cells (Azulay, 2019) .