Scientist III, Process Chemistry (Antibody-siRNA Conjugates)
Arrowhead Pharmaceuticals · Madison, WI · 3 wk ago
On-siteResearch$110k/yrFull-time
Responsibilities
- Optimize discovery-stage conjugation protocols for antibody-siRNA conjugates, improving yield, reproducibility, and product quality to enable scale-up.
- Develop GMP-ready, kilogram-scale conjugation processes, including site-specific and stochastic conjugation strategies, linker chemistry, and payload attachment.
- Work hands-on in the laboratory to design, execute, and optimize conjugation reactions, purification (chromatography, TFF/UF-DF), and analytical control strategies.
- Oversee and direct CROs/CDMOs executing process development and manufacturing activities, including setting technical direction, reviewing data, and ensuring timelines and quality standards are met.
- Characterize conjugates for DAR/siRNA-to-antibody ratio, aggregation, charge heterogeneity, and stability using relevant analytical methods (e.g., HIC, SEC, IEX, LC-MS, AEX).
- Lead technology transfer to internal and external manufacturing partners, authoring process descriptions, batch records, and development reports.
- Troubleshoot process and analytical challenges; design experiments to define process parameters, ranges, and robustness for kilogram-scale operation.
- Collaborate cross-functionally with discovery chemistry, linker/conjugation chemistry, analytical development, and CMC teams.
Requirements
- PhD in Organic Chemistry, Bioconjugate Chemistry, Chemical Engineering, or a related field; or a Bachelor's/Master's degree with commensurate hands-on industry experience.
- Demonstrated hands-on experience in siRNA conjugation development is required.
- Familiarity with oligonucleotide and/or antibody chemistry, linker design, and bioconjugation methods.
- Strong problem-solving, documentation, and communication skills.
Preferred
- Experience with antibody-oligonucleotide conjugates (AOCs) or antibody-drug conjugates (ADCs).
- Experience developing and scaling processes to GMP/kilogram scale and managing CRO/CDMO relationships.
- Knowledge of site-specific conjugation technologies (e.g., engineered cysteines, enzymatic/click chemistry).
- Experience with tech transfer and CMC/GMP environments.