Analysis of the Innovation Trend in Cell-Free Synthetic Biology

Round 1

Reviewer 1 Report

The paper goes in to some detail analysing trends in papers and patents published in the field of CFPS, breaking down and categorising by topic, geographical spread etc and looking for trends over time.  From this analysis they draw conclusions on the highest impact routes for future research in this area.

The paper is well written and clear to follow.  There is some interesting analysis and breakdown and the categories used seem largely sensible to the field.

Possible points for improvement:

I’m not convinced that the peak in patents in 2005 is fully explained.

Line 54:  do any of these references mention VLPs or vaccines?

Line 114-116: Is the link between commercial product availability and subsequent increases in papers published in the field corroborated by, e.g. references to the kits in these papers, or first availability of these kits?  It seems like quite a short time between the patent and paper spikes for commericalisation…

Figures 1, 2 & 4 – could be useful, for quick visualisation, to have a key on the figures.

Line 183:  what are spinout companies classed as?  Academia or company?

Figure 3b:  Does the number of patents per group differ for different geographical regions?  Might this be linked to the rise / fall or prevalence of different regions in the field?

Section 3.2 . 3.3:  Are patents filled by companies / academia on the same topic areas?

Line 237: “suggests continued growth” – i.e. suggests that growth will continue?

I think more work could go in to making clear the link between the analysis conducted in the paper and the conclusions reached.  Perhaps there needs to be a time line for the advent of particular new applications / formation of important companies in the field?

Will the raw/categorised data be made available?

Author Response

see attached file.

Author Response File: Author Response.docx

Reviewer 2 Report

This manuscript is for sure of interest to the CPFS stakeholders and is unique in its genre, probably it will attract many citations. The authors performed an accurate search of CFPS technology using public databases and manually removed non-pertinent publications, thus assuring the foundation for reliable results.

Interesting is the increase of publications/year corresponding to the development of the synthetic biology field, probably due to the increase of patents/year observed around 2005, which would provide more commercial products.

Valuable to know would be the most frequent definition used to describe the CFPS technology.

Notable the manual categorization into subtopics, giving the reader interesting insights on the diverse use of the technology, in particular, highlighting the efforts to increase the accessibility to a more efficient technology in terms of reducing costs and increasing protein yields.

Important for the adoption of the technology is the analysis based on the affiliation of the corresponding authors, which emphasize the growing interest of companies for the CFPS technology, mentioning in particular which groups filled more patens in industry and academia. Especially for the industry, this information is useful for readers interested in understanding the possible commercial applications of CFPS.

Interesting is the analysis of the distribution of efforts around the globe, although I believe would have been also interesting to analyze the number of patents filed and manuscripts published in India to have a more global overview also for investors that may be keen to read the paper. In addition, India could be an important landscape for use of the last developments of CFPS as point-of-care diagnostics and freeze-dried cell-free systems for on-demand biomanufacturing.    

Author Response

see attached file.

Author Response File: Author Response.docx

Reviewer 3 Report

Meyer et al. describe the trends on patent filing and manuscript publications with respect to cell-free synthetic biology. The authors gathered and curated a number of patents and publications based on the theme, affiliations, country, etc. While this can be of interest to people who are familiar with cell-free synthetic biology, a clear picture on use-case and merit of cell-free synthetic biology is lacking. In particular, the figures are all graphs (which can easily be delegated to supplement) and no pictorial explanations are given for cell-free synthetic biology, key applications, and future directions. The authors would need to greatly expand the manuscript to address the following issues. 

The authors need to provide at least the following figures and detailed descriptions.  There are so many references on cell-free synthetic biology that the authors should not find any difficult to create the following figures. 

1. Cell-free synthetic biology: general introduction

2. Key applications

3. Seminal papers 

4. Improved CFPS: historical trend in benchmark proteins yield (e.g., GFP)

5. Cost breakdown of CFPS (comparing several methods and commercial kits)

Author Response

see attached file.

Author Response File: Author Response.docx

Round 2

Reviewer 3 Report

The authors addressed some of the concerns expressed by the reviewer and improved their presentation.  While a further elaboration on the CFPS would be desirable, the manuscript in its present form may be acceptable.