MRC/UCB Antibody Discovery Initiative FAQs
What are the aims of the MRC/UCB antibody initiative?
- To provide academics with access to UCB’s novel single B-cell antibody discovery platform
- To deliver a high quality monoclonal antibody for academic drug discovery projects with clinical line of sight
- To provide an antibody research tool to enable investigation of mechanism of human disease
Who will own the IP?
- The academic groups will own arising project IP.
- UCB will have the first option to enter a negotiation to exclusively license any resulting programmes of relevance to the company’s therapeutic areas of interest.
What therapeutic areas are within scope?
- All areas – this call is NOT limited to areas of interest to UCB
- Exclusion criteria – existing or previous UCB projects, existing 3rd party arrangements, technical feasibility / tractability, existing commercial antibody products to the target
What constitutes a fundable project?
- Significant unmet need
- Strong scientific rationale
- Good evidence
- Technically validated
Is the call restricted to applicants with prior/current MRC funding?
- NO. The call is open to all eligible UK based researchers and organisations.
Is there a need for the immunogen and for screening assays to be in place before submitting an application?
- You should have a good idea of your preferred immunogen (see below) and of a possible screening assay cascade prior to making an application. Successful projects cannot be initiated until both immunogen and assays are available, although in some cases early plans can be further refined through the technical review with advice from UCB.
What are the technical requirements for the immunogen and why is it important?
- Intrinsic quality of immunogen is a critical success factor in the generation of an immune response producing antibodies specific to your protein of interest.
- It is important to consider the species from which the immunogen is derived and any desired cross-reactivity between species. Rabbits are frequently used for antibody generation, so for an anti-mouse protein antibody, information on the percentage identity between the mouse and rabbit proteins is required. Other animal species can be considered.
- Peptide, protein and syngeneic cells transformed with the protein of interest are all suitable as high quality immunogens. Areas for consideration include:
- Purity >90% by SDS-Page
- Low levels of aggregation <5%
- Low Endotoxin level (ideally <1EU/mg)
- Need to carefully consider the epitope to target, the rationale for its choice and likely cross-reactivity
- Conjugation to appropriate carriers (e.g. Ova, KLH, BSA) is required, and location of Peptide length (Justification for choice)
- Syngeneic Cells
- This is an option for membrane proteins (and occasionally secreted proteins where purified protein is not readily available). UCB can provide advice with this and can be explored at technical review.
What are the technical requirements for the antigen binding assays and why is it important?
- Having generated an effective immune response, typically 100 million B-cells are plated onto 500 x 96 well plates and are cultured for 1 week. The supernatant from each well is them initially screened for binding, typically using an homogenous fluorescence based assay (TTP Labtech Mirrorball device), although alternative formats are available (e.g. ELISA, flow cytometry).
- Efficient screening of 50,000 samples requires, reliable, consistent, sensitive, plate based assays suitable to automation.
- Where possible it is also important to demonstrate that antibodies bind to natively produced protein rather than recombinant tagged forms. The development of such assays is strongly encouraged.
What are the requirements of a functional activity assay?
- Master plates are created from wells containing confirmed binders, typically containing 150µl of B-cell culture supernatant for use in further assays. This can include epitope binning or cross blocking assays but ideally should also include an assay of functional activity
- A functional assay is typically a cell-based screen, although additionally/alternatively a protein-based assay may prove useful.
- It is advisable to consider more than one functional assay, and potentially an assay cascade.
- Complexity of the cascade will be dependent on the biology of the interaction being modified.
- Throughput will be determined by the compatibility of the screening system with supernatant, transient supernatant or purified samples
- If a functional assay cannot be used, then it may be possible to generate a small panel of antibodies to different epitopes of the target protein using a cross-blocking approach. However, this is inefficient, resource rich and time consuming. This would not be considered a preferred option and would significantly impact on the assessment of your proposal.
Where will the work be carried out?
- In the majority of cases the work will be conducted solely at UCB’s research facilities in Slough, UK.
What is the application process?
- A single stage Full Application process
- There is NO expression of interest or Outline application stage
What is the decision making process?
- A freedom to operate assessment will be undertaken by UCB prior to the applications being sent out for external Peer Review
- Prioritisation decisions will be made by an independent Panel (with NO UCB representation), comprised of representatives from MRC’s DPFS Panel, Research Boards and other experts.
- Prioritised applications will be assessed by a technical Panel, which will be responsible for feedback on additional work required, allocation of slots at UCB, and any follow-up funding
What are the timescales?
- Applications will be scheduled at UCB over the following 12 months, timing will be dependent on assay and immunogen readiness, and available time on the Platform.