Multiplex Genome Engineering using CRISPR / CAS Systems

CRISPR_Crystal_CAS9

 

CRISPR is a novel tool used in trail blazing research in an attempt to cure thousands of genetic diseases whose sufferers have little or no other hope of being cured. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has given scientists the ability to readily edit the human genetic map which could previously only been done with much difficulty.  Additionally, they hope that they might even prevent incipient diseases by gene editing embryos in the womb, a likely controversial use of the technology.

60 Minutes

60 Minutes CRISPR

 

A few years ago, journalist Bill Whitaker interviewed MIT professor Dr. Feng Zhang, the inventor of a novel way to bypass human genetic instructions using the CRISPR material.  At the Broad Institute, he and other researches are employing CRISPR to defeat diseases such as hemophilia, Huntington’s, sickle cell and other difficult to resolve infirmities.  In order to understand the CRISPR phenomenon one must understand the origins of their hopes.

60 Minutes CRISPR

60 Minutes CRISPR

Years ago, the Human Genome Project was an international endeavor focussed on the charting of the architecture and purpose of DNA amino acid sequences; the project began in 1990 and concluded in 2003.  Dr Eric Lander of the Human Genome Project described on 60 minutes how they could read the entire human genome, however, they knew of no way to cure any diseases.

 

 

The breakthrough came when researchers noted that bacteria retain a copy of infectious viral DNA in order to destroy future viruses.  In other words, bacteria make a copy of the virus material so that they could remember the previous attack and remove any future infestation before it gets out of hand.  As a result, Dr. Zhang figured out a way of using the CRISPR material in order to permit the fast editing of human DNA.

This is accomplished using an enzyme called CAS9 for CRISPR Associated Protein 9; this he used to make a map in order to locate and cut specific strand complementary to the CRISPR DNA.  The strands of material making up DNA are composed of four amino acids, namely, Adenine (A), Cytosine (C), Guanine (G), Thymine (T) arranged in an enormous series of information.  Therefore, using their knowledge of DNA, he could use CRISPR to remove any short string within the strand that was determined to be erroneous based upon the particular sequence of the above referenced acids.

In order to further research, Dr. Zhang has distributed the technology to over 2000 labs in 60+ nations.  The CRISPR frenzy had begun and it was not long before researchers were fast editing insects, foodstuffs, and animals to edit out disease propagating characteristics, improve crops yield and cure diseases.  All of these potential monumental modifications could mean large financial returns to the scientific teams and the institutions funding them.  Indeed, a patent fight developed between University of California Berkeley and Zhang’s team at the Broad Institute.

In September 2018, a Federal Appellate Court unanimously ruled in favor of Broad and Zhang in that Berkeley had not proven there case and that there was no interference between the CRISPR patents of the two pioneering groups.  The Berkeley group are undeterred and have even gone as far as to allege that information was withheld from the USPTO by Zhang and Broad.  There are even alleged emails from a Broad researcher that suggest that Zhang and his team only started their creations after reading the Berkeley discoveries.  CRISPR patent warfare is ongoing in Europe and it seems so far that the Berkeley team has the upper hand in Europe.  As Berkeley has basic patents issued in Europe and many other countries for CRISPR CAS9 genome editing, it will be an uphill battle for Dr. Zhang and the Broad Institute.

Official_European_Patent_Office_Logo

European Patent Office

 

Broad, MIT, Harvard along with the Zhang team received a 2015 patent for its Multiplex Genome Engineering using CRISPR / CAS Systems; however, the patent was eventually revoked over existing prior art as it lacked novelty.    They filed an appeal on the prior decision by the Opposition Division relating to a technical question citing Article 87 EPC.  It soon seemed that the appeal process would continue longer than expected even though the Opposition Division had ruled according to the existing EPO case law; thus, it was believed that the appeal would be referred to the Enlarged Board of Appeal.

Further communications from the two parties resulted in the regular Appeal Board deciding against Broad et al.  By upholding the previous decision the panel had invalidated the patent.  As Broad has stated that the same technical issues affects some of its other EPO patents, these others are also in danger of revocation on the same basis unless the interpretation of Article 87 EPC is changed.  Additionally, because the appeal was not bumped up to a higher group in the regular appellate process, only the European Patent Office President can refer the case to the Enlarged Board.  However, the EPO Presidential power is restricted to those occasions where Appeal Boards have ruled differently in preceding case law, and therefore it is believed that this may darken any hopes for a portion of the CRISPR European patents from Dr. Zhang and company.