Fig 1.
Application of Classification of Overlap Method (COM).
(A) UPC and CPC classes and time period used to implement COM; (B) Description of UPC and CPC classes; (C) Visual depiction of the 58 patents in the pre-set in the classes selected, an indication of completeness. White spaces indicate the patents not retrieved in this set; (D) Total patents retrieved and percentage of 58 key patents covered by the Pre-CRISPR patents.
Fig 2.
Patenting activity for genome engineering patent set.
(A) patents granted yearly 1999–2017; (B) Top 10 assignees (with formal names) New England Biolabs, Sangamo Biosciences, Harvard University (President and Fellows of Harvard College), University of California (The Regents of The University of California), WARF (Wisconsin Alumni Research Foundation), MIT (Massachusetts Institute of Technology), Stanford University (The Board of Trustees of The Leland Stanford Junior University), Boehringer Mannheim (Boehringer Mannheim Corporation).
Fig 3.
Patenting activity for CRIPSPR roots set.
(A) Patents granted yearly 1976–2017; (B) Top 10 assignees (with formal names): Univ of California (The Regents of The University of California), MIT (Massachusetts Institute of Technology), Isis Pharmaceuticals, Sangamo Biosciences, Life Technologies, Alza (Alza Corporation), Harvard Univ (President and Fellows of Harvard College), Broad Institute (The Broad Institute, Unger, Evan (Evan C. Unger), Caltech (California Institute of Technology).
Fig 4.
Steps for genetic backward-forward path analysis (GBFP) adapted from (17).
Fig 5.
Main path results for genome engineering patent set.
Three main paths (GE1, GE2 and GE3) have been identified. GE1: Cloning and restriction endonuclease (REs); GE2: core genome editing; GE3: Endonuclease and related enzymes. Labeled nodes represent patents and are identified in the side table with the patent number which allows one to search for and read the patent on various databases.
Fig 6.
Technology clusters in GE2 main path.
The patents in GE2 are identified in clusters of different technologies shown in the table in the upper left of the fig: (A) restriction endonuclease (RE) production technology; (B) separation of RE and DNA binding domains; (C) hybrid REs and genome engineering; (D) Zinc-finger nuclease (ZFN); (E) Therapeutic application of ZFN, TALEN, or CRISPR; (F) Transcription activator-like effector nuclease (TALEN); (G) Extending genome engineering to RNA level regulation. Nodes represent patents repeated from Fig 5 and the actual patent numbers are identified in the lower left legend in Fig 5.
Fig 7.
Main path for the CRISPR roots showing patents on this knowledge trajectory from the CRISPR patents (gen 0), the patents cited by the CRISPR patents (gen 1) and the patents cited by gen 1 patents but not by CRISPR patents (gen 2).
Three main paths (CR1, CR2, and CR3) have been identified. CR1: Technologies for introducing nucleic acid into mammalian cells; CR2: Genome engineering (including protein binding domains, ZFN and CRISPR); CR3: DNA finger printing and PCR. Labeled nodes represent patents shown in the table below the main path diagram. The node numbers increase along the time axis.
Table 1.
The ten top-ranked patents from the CRISPR nucleus according to information centrality.
Table 2.
Eight key patents in the main path and core of genome editing which are also in the CRISPR roots set.
Table 3.
The estimated annual improvement (k) in percentage for the genome engineering patent set (domain) and the CRISPR roots set.