Posts by: Joanna Applequist | (3) posts

Broad Institute maintains patents to Gene Scissors in the US

The CRISPR-Cas9 technology, the so called “gene scissors” which allow for targeted genome-editing, is subject to a patent dispute between two research teams lead by Jennifer Doudna at UC Berkeley and Emanuelle Charpentier then at the University of Vienna on one hand, and Feng Zhang’s lab at the Broad Institute and MIT on the other. At stake are the fundamental rights to the CRISPR technology, which may very well be the greatest, and most profitable, advance in biotechnology of this decade.

The battle has taken an unexpected turn in the US, where the Patent Trial and Appeals Board (the PTAB) of the USPTO on the 15th of February 2017 issued their decision stating that there is no interference-in-fact between several patents and patent applications owned by the Broad Institute and applications owned by UC Berkeley. In the decision, PTAB writes that Broad has persuaded us that the parties claim patentably distinct subject matter” and “Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment.” Thus, the PTAB decided in Broad’s favor. The decision neither cancels nor finally refuses either parties’ claims and therefore both parties are allowed to freely license and assert their right to any third party.

The background of the dispute is that the Broad Institute has received 13 patents on different aspects of the CRISPR technology since 2014, but the UC Berkeley team believes that they alone deserve patent rights to some core technology based on their earlier work.

UC Berkeley filed their first patent application on March 15, 2013 claiming priority from May 2012. They described genetically modified cells that produce the Cas9-enzyme, which is required for working the CRISPR technology, and the use of CRISPR-Cas9 in any setting and cell type.

In October 2013 the Broad team filed their patent application claiming priority from December 2012. The application described adaptations of the CRISPR technology to eukaryotic cells. Broad team requested accelerated examination which resulted in that they obtained 13 granted patents, including the original CRISPR patent, with claims to (very profitable) eukaryotic applications of the technology, even though the UC Berkeley team having earlier date of invention and earlier filing date still has not received any granted patent rights.

UC Berkeley attempted to speed up the prosecution proceedings before the USPTO and finally resorted to intentionally amending the claims in their application in order to achieve an overlap between the claim scope of their earlier filed application and Broad’s granted patents and pending applications. This in turn resulted in the instigation of Interference proceedings before the USPTO in order to determine which team was first to invent the revolutionary technology and thus had the right to obtain patent protection. 

On the 6th of December 2016, long after filing the written arguments, both parties were allowed about 40 minutes to orally present their arguments. Broad argued that the adaptation of the technology to eukaryotic cells was an invention in itself, while the UC Berkeley team held that Zhang’s adaptation of the technology to eukaryote systems was obvious and could have been done by a person skilled in the art of biotechnology based on the work of Doudna and Charpentier.

After almost two (long) months of waiting, the PTAB has now issued their decision meaning that Broad’s patents are not hindered by the UC Berkeley application.

The UC Berkeley team maintains that the Broad Institute’s patents are not patentably distinct from Doudna’s and Charpentier’s invention and have issued a statement that they are considering all options for possible next steps in this legal process, including the possibility of an appeal of the PTAB’s decision.

Joanna ApplequistPatent Attorney

An attempt to clarify what an embryo is

What is really meant by the term ”human embryo” as used in Article 6(2)(c) of the Biotech Directive (98/44/EC)? Are parthenotes to be considered as embryos and what is meant by “capable of commencing the process of development to a human being”?

Following an appeal by International Stem Cell Corporation (“ISCC”) against a decision that the subject matter sought protection for in two related applications is excluded from patentability as it relates to human stem cell, the UK High Court has referred a question to the Court of Justice of the European Union (“CJEU”). The subject matter of these patent applications relates to human embryonic stem cells (hESCs) isolated from oocytes activated by parthenogenesis, which is the initiation of embryogenesis without fertilization through the activation of an oocyte by artificial means in the absence of a sperm.

During normal embryonic development, the first few cell divisions give rise to cells that are totipotent (capable of differentiating into both embryonic and extra-embryonic tissues, such as the placenta). Already when the embryo consists of 100-200 cells and makes up a hollow sphere called the blastocyst, the developmental potential of a central group of cells called the inner cell mass has become restricted to embryonic tissues (pluripotent), while the outer layer of cells gives rises to extra embryonic tissues.

Scientific studies have shown that parthenotes of several species, which in contrast to fertilized embryos only contain maternal DNA, cannot develop to term. This is because paternal DNA is required for the development of extra embryonic tissues necessary for normal embryonic development. In particular, human embryos have been shown not to develop beyond a blastocyst-like structure. And, in contrast to a fertilized ovum, in the first few cell divisions after activation the cells of a parthenote are only pluripotent, not totipotent.

The CJEU gave guidance in the Oliver Brüstle v Greenpeace case (C-34/10) as to what is the correct interpretation of Article 6(2)(c), saying that the concept “human embryo” must be understood in a wide sense. Accordingly, “any human ovum must, as soon as it is fertilized be regarded as a human embryo since fertilization is such as to commence the process of development of a human being”. Also, any artificially manipulated ovum capable of commencing the process of development of a human being just as an embryo created by fertilization must be regarded as a “human embryo”.  Hence, any human ovum after fertilization, any non-fertilized human ovum into which the cell nucleus from a mature human cell has been transplanted and any non-fertilized human ovum whose division and further development have been stimulated by parthenogenesis constitute a “human embryo” within the meaning of Article 6(2)(c).

In the case at hand, ISCC argued that it was necessary to establish what the CJEU meant by “capable of commencing the process of development of a human being”. According to ISCC, the question is whether it means “commencing a process of development which leads to a human being” or whether this applies also to processes that are incapable of leading to a human being. ISCC submitted that the test adopted by the CJEU was clearly directed at the first alternative and therefore their inventions should not be excluded from patentability as their embryos never develop past the blastocyst-like structure. They argued that CJEU incorrectly assumed that parthenotes were capable of commencing the process which leads to the development of a human being. ISCC also pointed to the reasoning of the Bundesrichtgehof following the ruling of the CJEU in Brüstle, interpreting the CJEU judgment as permitting the use of hESC derived from non-viable embryos.

The Comptroller General of Patents (the UK patent office) argued that the test applied by the CJEU might refer only to the start of the process of development and did not require its completion and the birth of a viable human being. In doing so, he pointed for example to the phrase “as soon as fertilized”, as well as to similarities between early development of parthenotes and viable embryos. However, the Comptroller agreed that it was unclear whether the Brüstle test turned on commencing the process of development, or commencing the process capable of creating a viable human being.

The Deputy Judge decided a further reference was justified, based on the different factual matrix (the evidence before the CJEU was that parthenotes have the potential to create a human being whereas in the present data was presented showing that this is not the case) combined with the insufficient clarity of the test applied by the CJEU in Brüstle

Like the Advocate General in Brüstle, the Judge considered that a distinction should be made between totipotent cells and pluripotent cells. He emphasized that parthenotes and fertilized ova are not identical at any developmental stage. In his view, if the process of development is incapable of leading to a human being, as in the case of parthenotes, then it should not be excluded from patentability as a “human embryo”.  Also, the Judge repeated well known concerns of the biotech industry and academia and concluded with stating that the total exclusion from patent protection of the fruits of stem cell research would be “to the detriment of European industry and public health”. 

It appears as if the last word on stem cell patenting has not been said…  

Joanna Applequist, Associate

The question to be referred:

“Are unfertilized human ova whose division and further development have been stimulated by parthenogenesis, and which, in contrast to fertilized ova, contain only pluripotent cells and are incapable of developing into human beings, included in the term “human embryos” in Article 6(2)(c) of Directive 98/44/EC on the legal protection of biotechnological inventions?”

The case:       International Stem Cell Corporation v Comptroller General of Patents, Patents Court, London, UK, 17 April 2013, Case No. [2013] EWHC 807 (Ch)

Link:             http://www.bailii.org/ew/cases/EWHC/Ch/2013/807.html

“There is so much more to learn …” – first report from our Specialist programme

It is peculiar how all of a sudden all news media and even friends and family seem to discuss patents and intellectual property rights… Samsung vs. Apple (R.I.P. Steve Jobs), America Invents Act and EU-patents. Perhaps it is because when you start to work within a new field, you tune in things that used to pass you by.

Most of us, who started the Specialist programme close to six weeks ago, represent to some extent the best within our specific technology fields. It is therefore a somewhat odd feeling, finding ourselves knowing so very little… The more I learn, the more I realize how little I know… and to me this is quite exciting!

These past six weeks have revealed how multilayered and complex the role of a patent attorney is, encompassing science and technology, law and business, communication and salesmanship as well as writing, translations and grammar….  Who would have thought that at the age of 30 something I would be working on perfecting my Swedish grammar?

But it is a privilege to get the opportunity to learn and it is a lot of fun. Although, I must admit that is with a great deal of humility that I look back at the article in Ny Teknik entitled “Bara de riktigt duktiga kan bli patentkonsulter” (Only the best can become patent attorneys), published only days before we started the Specialist programme.

So far, it has been a little bit like the first day (or weeks) of school, realizing that there is so much more to learn… I am truly looking forward to the upcoming first home office period.

Joanna Applequist, Associate, Awapatent