Parthenogenesis derived Pluripotent Embryonic Cells are Patentable in Europe

Parthenogenesis - Bischoff, Steve R, 2010 - Duke University/ISCO

The significance of the ISCO Euro Court of Justice ruling positively hits on a number of fronts:

1. It is of course clear now that International Stem Cell Corp (ISCO) can be granted European Patents on their Parthenogenesis IP which gives them a distinct commercial position in the Pluripotent field in Europe.

2. Other Parthenogenesis programs can proceed to file & secure IP in Europe as a result of the ruling.

3. Existing Patent Applications that specify Parthenogenesis derivation methods as an "embryonic" cell source now have a clarified legal route to secure IP

4. Existing Patent Applications that specify "Pluripotent" derivation methods as an "embryonic" cell source now have a clarified legal route to include Parthenogenesis derived ES cells as a result of the ruling.

5. The combination of this clarification ruling on an activated unfertilized egg not being a "human embryo" by definition and the previous Non-Destructive language on use of IVF supernumerary pre-embryos clearly indicates a pathway to patent pre-embryo ES methods in Europe. An extracted Blastomere cell from a post fertilization state isn't capable of developing into a human independently and as long as its extraction doesn't do harm the 4-8 cell the pre-embryo can develop into an human, as it's potential is maintained, but only if it continues to correctly divide and post its implantation in the mother's womb will it have a chance to develop. The Non-Embryonic-Destruction ("NED") issue has already been indicated by the EPO's examination documentation on hESC Patent Applications and punctuated recently by Issuing Patents to hESC methods to derive human cells conditional upon NED technology tools being used (see Hadasit Medical / CellCure / BTX hESC RPE Patents). 

How does this ruling reflect on Ocata Therapeutics, as they were a primary Licensee to ISCO of their Parthenogenesis IP estate and maintain an interest in hpESCs as a Pluripotent source in their own IP assets?

While ISCO has got a ruling that works well for them, after much effort to get their science understood, the issues for Ocata in Europe are more layered...

As I outlined in the comments above there are directly positive aspects to the outcome in this case which can be extended to the Ocata & the sector, namely:

Pathogenesis is a Patentable Method and Product in Europe as it isn't a technology to create human life. As such anyone wishing to develop innovations using Parthenogenesis can do so with a path to secure IP around their programs. Ocata have covered the use of Parthenogenesis directly in Patent Filings (EPO RPE Apps for instance) and also in the "Pluripotent" manner which covers all sources of ES cells... so this directly and positively relates to Ocata's hESC Apps which include hpESCs and general Pluripotent language in their Apps.

On the issue of NED cell lines and Blastomere this ruling confirms the German Courts findings that the viability of a pre-embryo or capacity to develop into a human is critical to determine when considering whether there is scope for Patentability. The European Court left it to the National Courts to decide, if required, whether there is viability to an embryo. If an embryo for example arrests naturally it therefore has no ability to develop into a human and therefore its use is non-destructive and patentable in Germany for example (as they have done), according to their view of it. This seems logical and correct. If on the other hand a viable embryo is destroyed for its cells - in the case of Blastocyst technology (BioTime, WARF et al) - then there are no grounds for Patentability. If a non-destructive process is used to extract a Blastomere and the remaining pre-embryo remains viable that is also a non-destructive technology and one which the EPO has indicated is ok as a means to derive ES cells and patent the methods related to innovative cell related science (i.e. RPEs... for example). So this all bodes well for Ocata's hESC derivative Methods & Products.

Ocata has edited in their most recent continuation submission to their earliest Blastomere priority related application & paved the way for EPO acceptance as a non-human (mouse) method of NED cell lines (intention to grant was issued Dec 18th 2014). This looks like it will establish the precedent for the later Blastomere priority which is based on Human cell methods. The issues here remain language, ES co-culture methods, NED viability & use interpretations etc at the EPO, irrespective of the European Court of Justice's opinion on Parthenotes. However, this is true generally of the EPO as they are a separate body to the European Institutions. Their most current leaning on the subject can be seen in the recent documentation relating to the mouse patent (below) which includes an acknowledgement of innovation in respect to a Blastomere extraction versus the inefficient & destructive "classical" inner cell mass removal Blastocyst process... 

To continue, Ocata also has IP that relates to eggs which includes Parthenogenesis techniques and can win Patents in Europe now either using non-destructive hESC NED lines and/or via hpESCs or other Pluripotent sources.

Further, SCNT as a method to create ES cells would I believe fall within the Parthenogenesis ruling as the techniques involved to "activate" the egg would follow the same argument as ISCO's Parthenotes above...

The use of pre-existing IVF supernumerary for SCNT ES cell lines is less clear as it involves an existing viable fertilized pre-embryo (hundreds of thousands in deep freeze) unless the pre-embryo was deemed unviable post thaw and could serve the purpose of being a home for SCNT ES development.

The issue here is the Egg versus a Fertilized Egg (viable pre-embryo) - if you use an Egg in SCNT Methods and produce ES cells you would need to prove that you are not creating anything viable in terms of human life, as there are issues with regard to germ cell manipulation and cloning.

Bottom line is the ISCO/Parthenotes ruling was v. positive for ISCO primarily but also Ocata and other hpESC/Pluripotent source programs.  


Creation, Ensoulment, Birth & The Ethical Use of a Donated Cell

School of Athens” by Rafael w/ Plato and Aristotle - referred to by
Pope Francis during EU Parliamentary address Nov 25, 2014
There is a bridge between the opinions that divide us on this subject. I have written a number of times on the Middle Way, a Compromise if you will, that will heal the scar and abate the fear.

There is an ethically sound scientific process to allow for a donated Pluripotent stem cell from Human pre-embryos to be used for medicine.

The cellular process of embryogenesis has been studied at great length. The fundamental origin of Human Life is indeed the Creation of a pre-embryo – that Sperm and Egg moment and the days thereafter of cell preparation for a Mother’s acceptance. This fertilization moment and the immediate cell divisions after are central to the beginnings of Healthy Physical Life. This understanding is universally acknowledged.

The success of that biological union in the combination of DNA from both parental sexes (male & female) provides the early catalytic events that set in motion the journey to deliver a full term baby. The process is clearly not perfect by anyone’s measure and doesn’t at all guarantee stepwise progress nor a healthy outcome. There are a number of important & vital moments along the way – most importantly to all is the Mother’s acceptance of the pre-embryo into her uterus via the Implantation process around Day 8 or 9 post fertilization.

The period before Implantation is referred to as the “pre-embryo” phase, as it is clear from the scientific evidence and analysis that the cellular process of developmental Life isn't sufficiently complete to begin the formation phase of Human Life unless these early individual cells develop to the Blastocyst stage, are accepted and successfully embedded in the uterus wall of the Mother. Unless that happens a woman will pass the pre-embryo cells out of her system, as she does with the uterus walls during her monthly period cycle. Some women never accept a pre-embryo into their uterus as a result of many possible problems, including the genetic instability or malformation of the combined DNA nucleuses. Some women can only conceive with IVF assistance and pre-embryo screening help.

IVF is not the topic here so I will leave that for others to continue to debate its validity as this blog article is in reference to the pre-embryo period and the possible non-destructive removal of a single cell during this post-fertilization phase prior to Implantation.

Fertilization and the pre-embryo period is a starting cycle without which Human Life couldn't develop, yet it is still merely a starting signal for the remaining many phases that will confirm and define what it is to Be Human.

The scientific distinction is as clear as an Egg and Sperm. A pre-embryo is the union of DNA strands ready to embark on the journey to create a Human. A ball of intelligent cells pre-programmed to develop if the formation is correct, the proper signals received and the internal script processed successfully. An embryo is the resultant accepted & developing Lifeform once embedded in the Mother’s uterus. A Fetus is an established growing person with a beating heart and developing brain within the Mother’s womb. These stages of Life are clearly delineated by the process itself. Science merely exposed what Nature has already defined. The success ratio of Nature is nowhere near perfect in this process, as naturally fertilized ovums are discarded regularly and assisted conception ratios low.

What is important to note here is the difference between a pre-embryo, an embryo and an Human Fetus.

Needless to say all stages are Life and should be duly respected.

Healthy Human Life can and does develop from a pre-embryo after one cell is extracted for analysis and medically screened while the remaining pre-embryo cells continue to divide and develop. The same biological process is required for all pre-embryos to be accepted into and nurtured by the Mother’s uterus – including the one that had a cell extracted for genetic screening. Healthy babies are born every day using various cell extraction screening techniques, free of genetic issues as a result.

The confusion here is that during these past years of discovery cells were used from leftover & donated pre-embryos that were not needed any longer by couples that had fertility treatment to conceive. These pre-embryos were donated and had their cells removed in a process which terminated the pre-embryo’s development. This method of obtaining cells via donated pre-embryos for science continues. This method of cell extraction isn't necessary as a cell can be extracted from an earlier stage pre-embryo using a technique called Preimplantation Genetic Diagnosis (PGD), which is used daily by fertility clinics world-wide. It can and should be used as the method of choice to extract a Pluripotent cell from a pre-embryo in order to screen for genetic issues while also enabling the process of scientific discovery & cellular science. A Pluripotent cell is not a pre-embryo nor is it capable of developing to become a pre-embryo or embryo. The use of this PGD process can & does maintain the integrity of the pre-embryo state and it’s potential, while allowing for genetic screening & vital treatments for those that suffer from disease. One does not negate the other.

While I can appreciate the moral dilemma with respect to those that feel a pre-embryo is a Human Life, I must differ in that the science has proven that Human Life isn’t yet defined in these cells. There is Biological Life of course present and the potential to develop further into a Human but it isn’t sure whether it may or may not have the integrity to be viable nor capacity to develop further. It isn't sure either that the Mother’s system will accept the pre-embryo into her uterus and begin the developmental process of formation to become what is defined by all as being Human. This process is dependent on a number of natural system checks and balances. It has been revealed that a successful pre-embryo must first properly create a DNA construct and divide correctly to the point of being presentable to the Mother’s uterus. Incorrectly formed pre-embryos don’t, in almost all cases, pass this initial test. To say that an incorrectly formed pre-embryo that is rejected by the Mother’s system is a Human is wrong. This would by extension apply also to a pre-embryo that seems to have the right cellular makeup but still doesn't get accepted by the Mother’s uterus for other natural selection reasons. There are chemical signals within the Mother’s body that function as a viability filter and She initiates acceptance & provides the signal environment for Human organ development post Implantation. So unless a pre-embryo embeds in the uterus we cannot begin to be classified as Human as we haven’t started to emerge from that pre-embryo ball of cells and take shape. Even then the issue of the many and correctly passaged development stages of the embryo into a Fetus lies ahead.

Our Churches, Temples & Shrines aren't the sole purveyors of ethics and moral standing in our community. They certainly can help us along the path but we must all accept our own responsibility to understand and draw conclusions on the reality of our progress as a society. If Religion is anything it is a bellwether for the community and when some within the community need its guidance it has a duty to inform and guide based on the best interests of the people themselves, by disseminating knowledge and wisdom in a practical and spiritual context.

I say this as it has long been debated whether pre-embryo cells from donated IVF fertility treatments are sound ethical starting blocks for medical science. Will this still be the case when the truth is known that pre-embryos need not be destroyed and their potential maintained?

It is my opinion that to negate the progress of medical science in assisting the creation of Life is tantamount to ignoring Man in their quest for Love & Happiness. Especially if it doesn't harm the potential of further Life becoming a reality. It is also important to acknowledge that while assisting Life science has opened a door for simultaneous treatment of the sick. Life and Treatments together in one, as God intended.

Will there be criticism when medical science proves that Mother Natures’ most important cells – the potential Life forming pre-embryo cells – are used for the living that suffer and provide needed relief? Or will the misunderstood concept of the need to destroy prevail while the true facts of early Life processes, the nature of an independent cell state & its developmental knowledge be withheld from God’s people?

Pre-embryo cells can be taken without harm to the potential of Life and donated to help the living. Tissue willingly provided, as is done regularly today with blood and organs. A child can be born only when a pre-embryo is accepted by a Mother’s uterus, develops and successfully grows to term.

A day 3-4 Morula stage cell extraction does not destroy the potential to create Life. 
Later stage cell extractions at the Blastocyst Stage terminates the pre-embryo.
Ensoulment is by a far the greatest gift to Human Life – for without it we would be unconscious. Consciousness defines our Personhood, our Self. It is the defining characteristic that allows the physical to exist and the non-physical to be reasoned. One could say that this component of Humanity is Divine. It certainly is one of the central tenets of Religion and for which a valued guide in our community is sought.

Throughout the History of Christianity there has been an overriding concept debated within the inner halls of the Institution itself – Ensoulment and when it occurs.

More clearly than ever today is the molecular insight into the developmental phases of the origins of Human Life. This in itself requires the ethical and moral concepts of the day to be reflected upon.

Terminating a pregnancy – once it is established in the Mother’s womb – has always been an immoral act in the eyes of the Christian Church. In certain circumstances the willful termination of a developing Life was considered unavoidable if the Life of the Mother was at risk. The implications of this Human Act in the eyes of the Catholic Church was Excommunication as the punishment, in most cases. However, this was not universally true throughout history as there was a clear separation between the ethics of the immoral act of terminating a Life willfully and the punishment itself, if it was performed early in the developmental cycle post fertilization.

It seems the “Ensoulment” moment was the dividing line. A uniformly accepted believe for most of recorded history as occurring after a period of weeks post fertilization. Therefore the doctrine of a Human Life’s relationship to God, beyond the potential of a developing Lifeform, was enshrined in the Church’s teachings in this fundamental Ensoulment moment. These philosophical discussions within the Catholic Church are a documented series of changing positions dating back to the beginnings of the Christian Church.

When the issue was debated it was framed by the obvious question of at what point in the development of a Life in the Mother´s womb is that Life considered Human with a Soul and therefore one with God.

That Ensoulment moment was long considered 40 days after fertilization at a minimum for a male Fetus and 90 days at the outside for a female Fetus. The documentation dates back thousands of years to the Ancient Greek scholars & Aristotle in 350 BC. However, even at that time there were contradictory opinions that held the Soul entered at the moment of conception. The teachings of Aristotle of a later Ensoulment moment became widespread by the time of Augustine in the fifth century as the concept of stage development of a Lifeform from vegetative to animal to Human became accepted. Prevailing Christian thought became documented in the 12th century by the preachings of Thomas Aquinas and the Council of Vienne to that of Aristotle. Yet subsequent Popes differed on the doctrine of excommunication on the basis of formed versus unformed Fetuses and the topic of Ensoulment as a consequence. Early Church theologians attempted to bridge this divide with a Casuistry compromise that allowed for non-ensouled Life to be regarded as different than that of an ensouled Human Life. Since the eighteenth century the Church has considered Human Life beginning at conception along with Ensoulment. Needless to say this debate has raged in the Church since it’s inception as an Institution.

What is apparent from a lay perspective is that the Church has adapted its own views to the popular reality of the day and considered scientific facts, as presented. The difference between then and now is fundamental in that today there is molecular science and it has revealed to all the embryonic process and the value of the cell in curing the living.

As the reality of the day becomes the norm, there is and will be assisted births, genetic treatments and cellular science derived from the earliest stage of Life (naturally conceived, programmed or reprogrammed). An altered series of biological interventions by science in the process of serving his fellow man.

This process can be done without destroying a naturally fertilized union between an Egg and Sperm. There are many ways to create that don’t destroy. There is a need to accept and understand what the difference is between the viability to create Life, the potential of cells and Human Life itself. Without bridging the divide on the issues a meaningful opportunity to engage and grow stronger together will be lost.

There is no question in my mind that there is a Duty in respecting existing and developing Human Life Implanted, Developing & Ensouled in the womb through all possible means.

Medical assistance by way of Non-Destructive cell science for the benefit of those in need is similarly a Duty and Humane.

Blood & The Search For A Universal Drug Delivery System

The doctrine that we are all equal under God applies in reality to the very Blood of humanity that runs through our veins. This was the shocking truth that changed an age old way of intellectual & class division. After millennia Science did that not faith. The fluid of life is an interchangeable commodity that drives the body and mind. A genetic brain unique to a person's cells is common enough to be of practical benefit. Donors of all types, colors and creeds can have some siphoned off and provided to those that need a refill. 

We accept the DNA of another to live on, with new Blood, without question and without any harm.

With 7.2 Billion humans on the planet you would think that we'd have enough of the Red stuff to go around. Think again. We don't even have enough fresh supplies to meet current demand, let alone future requirements based on the donation system. How can we expect this system to suddenly change to meet the forecasted demand when the population hits 10 Billion within a few decades and then 15 Billion a generation or two later?

Enter science, as usual, to solve the human evolutionary dilemma - Create it.

Not only is it possible to do so now, in inexhaustible volumes to satisfy all, but those cell products can and will be modified by the Scientists & Doctors of this 2nd Blood Revolution to deliver the needed solutions against the parasites, funguses, viruses, bacterias et al. that plague & kill daily in countless numbers.

Engineered weapons of the vascular system that naturally hone in and destroy invading pathogens.

The below provides a rough summary of how this is coming together from the perspective of ACTC and it's scientific colleagues.


Phase 1 - Blastomere Derived Renewable Stem Cell Line
Phase 2a - Clinical Expansion & Banking of Hemangioblast Derived Megakaryocytes
Phase 2b - Engineered Variants for Drug Delivery Requirements
Phase 3a - Differentiation of Platelets, Red Blood Cells & Line Derivatives 
Phase 4a - Biocompatible Unit Preparation & Universal Distribution
Phase 4b - Locally Served Fresh Product via Bioreactor Automated Production



Cell Research Jan 2011 - "Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice" - SCRMI, Univ of Illinois Chicago, Cha Univ, Harvard / BWH & ACTC 

Blood July 2014 - "Platelet bioreactor-on-a-chip" - Harvard / BWH, Univ Colorado & Colorado School of Mines, McGill, ACTC

Vector - Boston Children's Hospital Blog March 2014 - "The Platelet Whisperers

MedCity News April 2014 - "Biochip mimics how the body produces platelets so they could be made in a lab"

NY Times May 2014 - "Young Blood May Hold Key to Reversing Aging"

UCSF July 2014 - "Key to Aging Immune System Is Discovered

Proceedings of the National Academy of Sciences of the USA, June 2014 - Whitehead Institute & MIT - "Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes"

The Scientist Sept 2014 - "Next Generation: Blood-Cleansing Device" - (Engineered MBL Protein use example in fighting Sepsis - with cell engineering it can be done without dialysis)

Advanced Cell Technology's Scientific Advisory Board

Dr. Langer's Lab & Dr. Jensen's Lab of MIT

The Scientist July 2013 - "Narrow Straits - Transfecting molecules into cells is as easy as one, two, squeeze.

Proceedings of the National Academy of Sciences of the USA, Feb 2013 - "A vector-free microfluidic platform for intracellular delivery"

R&D, July 2013 - "Researchers put squeeze on cells to deliver"

Dr. Daley's Lab - "Hematopoiesis Research" - HHMI / Children's Hospital Boston / Havard  & "CellNet" - Children's Hospital Boston / Havard / Boston Univ & iPS mRNA Tech

Daley / Children's Hospital Boston / Harvard Patent Families: 

Biomechanical Induction of Hematopoiesis
Inhibition and Enhancement of Reprogramming by Chromatin Modifying Enzymes
Methods for Enhancing Hematopoietic Progenitor Cell Engraftment 
Method to Produce Induced Pluripotent Stem (iPS) Cells from Non-Embryonic Human Cells 
Method of Enhancing Proliferation and/or Hematopoietic Differentiation of Stem Cells

Advanced Cell Technology's Patent Portfolio for the Blood Program:


Blastomere Non-Destructive Human Embryonic Stem Cell Technology 

Blastomere Patent Family

5 Granted US Patents: 1, 2, 3, 4, 5

iPS/Reprogramming Renewable Stem Cell Derivation papers 1 & 2

iPS/Reprogramming Renewable Stem Cell Patent Family Portfolio: 1, 2 with examples A, B, C and SCNT Tech


HEMANGIO-COLONY FORMING CELLS - US Patent Granted & Patent Family 



STEM CELLS UNDER STROMAL-FREE CONDITIONS - PCT Pub June 2011 & US App Pub Dec 2012 & Patent Family  
(Note: SCRMI is a JV between ACTC & Cha Biotech of Korea - North American Rights belong to ACTC - Japan/Korea to Cha - ROW split)


Synthetic Biology & Process vrs Product - is this the Stem Cell sector's next big commercialization challenge?

It has been ruled on by the Supreme Court and Affirmed in Federal Appeals Court and at the USPTO that naturally occurring biological matter cannot be exclusively owned. This was today confirmed again in the matter of Roslin Institute's desire to Patent the "clones" of their SCNT cloning process. After years of examination rulings and a lengthy legal challenge, the Federal Appeals court upheld the decision of the USPTO that no Patents will be issued on the product of the process that created Dolly, as it produced a copy of a nature, and therefore "Dolly's genetic identity to her donor parent renders her unpatentable." Further, Judge Dyk stated that "There is nothing in the claims...that suggests that the clones are distinct in any relevant way from the donor animals of which they are copies."

The issue at hand is pertinent and important to note in that cells themselves are natural biological products, aren't they? Therefore they themselves, if unaltered scientifically, wouldn't be Patentable themselves therefore. The Process yes but the cell itself, if identical to the naturally occurring original, wouldn't?

Processes in the stem cell field are seemingly never ending...

The "product-by-process" standards that have applied to determining patentability by limiting duplicate product patents will need to be revisited to narrow the "product" window to only unique synthetic constructs. This developing legal framework of patent scope now calls into question old technology product claims and may give rise to a freedom to operate latitude the Courts are indicating on natural biological ownership.... or am I missing something here?

Are cells which are innovatively derived also being pushed to be genetically altered as a synthetic variant of the original as a requirement to secure a firm path to market?

Is an RPE cell derived from different innovative methods, such as hESC, iPS, SCNT, hpESCs, subject to a novelty test against an existing natural RPE cell in order to secure product claims? Will there be a race to alter the cells to create genetically unique versions in relation to the natural standard and the competitive versions?



Dolly the Sheep-type clones ineligible for patent: appeals court
BY BERNARD VAUGHAN - Thu May 8, 2014 6:45pm EDT

(Reuters) - The method for cloning animals such as the famed Dolly the Sheep can be patented, but the resulting animals themselves cannot, a U.S. federal appeals court has ruled.

"Dolly's genetic identity to her donor parent renders her unpatentable," Judge Timothy Dyk wrote Thursday for the U.S. Court of Appeals for the Federal Circuit in Washington, D.C.

Pilar Ossorio, a professor of law and bioethics at the University of Wisconsin Law School, called the decision a victory for people who thought cloning animals was morally wrong.

"This ruling is taking away an incentive for research organizations to pursue more research into cloning, at least on the margins," she said.

Scientists Ian Wilmut and Keith Campbell of the Roslin Institute of Edinburgh, Scotland, generated international headlines and intense ethical debates in 1996 when they created Dolly the Sheep, the first mammal to be cloned from an adult cell.

Dolly, named after country singer Dolly Parton, was euthanized six years later after she was diagnosed with a progressive lung disease.

The institute, which owns a patent to a method of cloning called somatic cell nuclear transfer, applied for a patent over the clones themselves but was rejected by a U.S. Patent and Trademark Office examiner in 2008.

In February 2013, the USPTO affirmed the examiner's decision, saying the clones did not possess "markedly different characteristics than any found in nature."

In affirming the USPTO, the Federal Circuit said that nature, natural phenomena and abstract ideas were not eligible for patent protection.

Salvatore Arrigo, a lawyer for Roslin, said he was disappointed with the ruling.

"There's no doubt in anyone's mind that Dolly is man-made," he said.

Roslin had argued that its clones were distinguishable from their donor mammals, in part because environmental factors could make their shape, size, color and behaviors different than their donors.

The Federal Circuit disagreed, noting that Roslin itself had said that such differences were produced "quite independently of any effort of the patentee."

"There is nothing in the claims...that suggests that the clones are distinct in any relevant way from the donor animals of which they are copies," Dyk wrote.

The USPTO declined to comment.

The case is In re Roslin Institute (Edinburgh), U.S. Court of Appeals for the Federal Circuit, No. 1407.