NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

I think there is a simple misunderstanding here. That patent has nothing to do with the DCVax-L P3, imo. And it makes sense why they would not change process part way through their trial. They said this in their Sept 2013 PR:

This next generation system has already been cleared by FDA for use in the manufacturing for NW Bio’s clinical trials. These systems are now in use producing the vaccines which already have been injected into the tumors of DCVax-Direct patients.

And no where in the PR will you find them saying this system is in use in the DCVax-L trial.

http://www.nwbio.com/nw-bios-patent-portfolio-further-expanded-with-manufacturing-automation-patent/

They did so in the Direct study because they only developed the system fully just before the first patient was dosed. They had already dosed many patients with the "old" system in the DCVax-L P3.

Also I don't think that's what they were implying in that mention in SEC filing. Here's the full mention from June 2012:

With biologics products, “the process is the product”: i.e., the manufacturing process is considered to be as integral to the product as is the composition of the product itself. If any changes are made in the manufacturing process, and such changes are considered material by the regulatory authorities, the company sponsor may be required to conduct equivalency studies to show that the product is equivalent under the changed manufacturing processes as under the original manufacturing processes, and/or the company sponsor may be required to conduct additional clinical trials. Our manufacturing processes have undergone some changes during the early clinical trials. Accordingly, we may be required to conduct equivalency studies, and/or additional clinical trials, before we can obtain product approval, unless the regulatory authorities are satisfied that the changes in processes do not affect the quality, efficacy or safety of the product.

https://www.sec.gov/Archives/edgar/data/1072379/000114420412037417/v315727_s1.htm

If those equivalency studies would be requested they would be after FDA reviewed the BLA, not before. And they are almost certainly talking about changes in manufacturing process from UCLA P1 studies (using UCLA's own clean room) to Cognate manufacturing for the P3 (obviously a diff facility and at least somewhat different process). Or their switch from acid-eluted peptide loading to WTL loading. But I don't think they are talking about changes made during the P3 study, as that's highly inadvisable (ask Larry Smith for his opinion on that). It would throw into question the validity of data. Regulators may even consider results uninterpretable.

Here are some other mentions from that same 10-Q to consider:

Multiple late stage clinical trials of DCVax-L for GBM, our lead product, may be required before we can obtain regulatory approval:

Typically, companies conduct multiple late stage clinical trials of their product candidates before seeking product approval. Our current Phase III 300-patient clinical trial of DCVax -L for GBM is our first late stage trial. We may be required to conduct additional late stage trials with DCVax-L for GBM before we can obtain product approval. This would substantially delay our commercialization. There is also some possibility that changes requested by the FDA could complicate the application process for product approval. In addition, a number of products are under development for brain cancer and at least one has recently been approved in the US. It is possible that the standard of care for brain cancer could change while our Phase III trial is still under way. This could necessitate further clinical trials with our DCVax -L product candidate for brain cancer.

and then right after this they say:

We face extensive competition from companies developing new treatments for brain cancer. These include a variety of immune therapies, as mentioned above, as well as a variety of small molecule drugs and biologics drugs. There are also a number of existing drugs used for the treatment of brain cancer that may compete with our product, including, Avastin® (Roche Holding AG), Gliadel® (Eisai Co. Ltd.), and Temodar® (Merck & Co., Inc.), as well as Novocure’s electrotherapy device.

GLTA