Goodbye Dolly. In re Roslin Institute (Edinburgh) ( ; May 8, 2014; Federal Circuit)

Transcription

1 Goodbye Dolly In re Roslin Institute (Edinburgh) ( ; May 8, 2014; Federal Circuit)

2 The History of Dolly Early, Scientists at the Roslin Institute clone two sheep, Megan and Morag, from differentiated embryo cells August 31, 1995 GB is filed July 5, 1996 Dolly ( 6LL3 ) is born August 30, 1996 PCT/GB96/02099 is filed February 19, 1997 USSN 08/802,282 (USPN 6,147,276) February 22, 1997 Roslin announces existence of Dolly January 4, 1999 USSN 09/225,233 (at issue) 14 February 2003 Dolly is euthanized November 5, 2005 USSN 11/265,113 (USPN 7,514,258) February 5, 2013 BPAI affirms Examiner s rejections May 8, 2014 CAFC affirms Examiner s rejections

3 Roslin Institute (Edinburgh)

4 Dolly s Inventors Sir Ian Wilmut, OBE FRS FMedSci FRSE is an English embryologist and Chair of the Scottish Centre for Regenerative Medicine at the University of Edinburgh Dr. Keith Campbell ( ), Professor of animal development at the University of Nottingham, Head of Embryology at PPL Therapeutics Jointly awarded the Shaw prize for medicine and life sciences in 2008

5 Dolly Science Somatic Cell Nuclear Transfer 1. Remove nucleus of somatic cell arrested at quiescent phase (G 0 ) 2. Implant somatic cell nucleus into enucleated oocyte 3. Implant created embryo into a surrogate animal Somatic cell - any differentiated body cell other than gametes Oocyte - female gametocyte

6 T EAW B1 I4RB CIHR,CSHT S EW RA T RT, K OKLOALSACSHC H & & B IB RICRHC,HL,LLPL P

7 What is a Clone? Exact genetic replica of the adult mammal from which the somatic cell nucleus was obtained But is Dolly really a clone? Epigenetics: stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable (methylation, histone modification, microrna, prions, srna, etc.) Mitochondrial DNA is from surrogate

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9 Dolly: Not the First Clone 1952: John Gurdon of Oxford University, South African frog 1963: Carp 1984: Dr. Steen Willadsen at the Institute of Animal Physiology in England claimed that he had cloned a live lamb from an immature sheep embryo cells through the process of nuclear transfer. 1986: Mouse (from ES cells 1994: Dr. Neal First, U. of Wisconsin clones calves from embryos that had grown to 120 cells. 1995: Megan and Morag Welsh mountain lambs, cloned from cultured, differentiated cells 1996: Dolly

10 Why clone anything? To further human medical practice To manufacture human proteins (Factor IX, etc.) To engineer whole genomes To genetically engineer animals to make drugs To create better crops and livestock To recreate extinct species In January 2009, an extinct animal, the Pyrenean ibex, was cloned, at the Centre of Food Technology and Research of Aragon, using the preserved DNA of the skin samples from 2001 and domestic goat egg-cells. To establish stable animal models for diseases To make stable banks of stem cells To recreate a deceased pet To clone humans, of course

11 USSN 09/225,233 Filed in January, 1999 First claims were PxP directed to reconstituted non-human mammalian embryo and animal produced by same, having same set of chromosomes as another individual animal 5 years of contentious prosecution with all claims consistently rejected in light of prior art and for various 112 deficiencies throughout prosecution 2006, TD s filed with Notice of Appeal; 218 page Appeal Brief 2008 BPAI affirms Examiner 2009, TD s filed with Notice of Appeal, 126 page Appeal Brief 2013 BPAI again affirms Examiner

12 Claims from ~ 2002

13 Representative Claims 1 st Appeal

14 BPAI Decision - 1 st Appeal, 2008 product-by-process claims are claims to the product itself, and are anticipated by the prior description of any product, no matter how made, that is the same as, or substantially the same as, a product made by the recited process. Differences are patentably significant only to the extent that the different subject matter is encompassed or excluded from the scope of the claimed subject matter. Clone = not new, not patentably distinct from naturally occurring animal = not patentable

15 BPAI Decision - 1 st Appeal, 2008 But are they different? Occupy a different space Exist at a different time Epigenetic/phenotypic differences Space/Time: Trivial and true of any two separate objects Phenotypic: Trivial, animals are complex and are normally somewhat different, any two separate objects will never be exactly identical on some scale Claims are not directed to something new within the meaning of 35 U.S.C. 102 Thus, claims are not patentable under 35 U.S.C. 101

16 Claims 2 nd Appeal

17 BPAI Decision - 2 nd Appeal, 2013 Restated issue: under what circumstances, if any, is a copy of a pre-existing thing patentable subject matter within the meaning of the applied statute? Is a clone patentable or a product of nature? No findings of technical facts are identified as leading to errors in the conclusions drawn in previous opinion Disagreement centers on application of law Roslin: clone is a structural limitation = structurally identical copy of parent Court cites the Mayo line of cases and Bilski

18 BPAI Decision - 2 nd Appeal, 2013

19 BPAI Decision - 2 nd Appeal, 2013

20 BPAI Decision - 2 nd Appeal, 2013 The clones do not differ genetically from their nuclear donor; the goal of a clone is to be as identical to the donor as possible Phenotypic (epigenetic) differences do not change a clone (structurally) to a non-clone Nonetheless, are there any differences, and are the differences sufficient to make clones patentable? Differences alleged by Roslin: Color patterns - Time-delayed genetic copy Iris patterns - Epigenetics Behavioral differences - The clone is living

21 BPAI Decision - 2 nd Appeal, 2013 None of these differences were convincing. Even if time-delayed, its still the same stuff Phenotypic differences do not rise to the level of a thing having a distinctive name, character, and use from the donor. The fact that its living which allows it to be cloned again is not convincing. Court cites In re Bergy, we think the fact that microorganisms are alive is a distinction without legal significance and that they should be treated under 101 no differently from chemical compounds.

22 BPAI Decision - 2 nd Appeal, 2013 Roslin argues that the Myriad decision supports the conclusion that clones are patentable; the clone has been isolated from the normal biological process. Clones reduce a portion of nature, a single donor mammal s genetic information, to a concrete form, a clone with intact genetic information of the donor. But its still a phenomenon of nature Any differences, such as epigenetic, do not involve the hand of man

23 CAFC Decision Even before Myriad, we all knew that naturally occurring organisms were not patentable (citing Chakrabarty, Funk, etc.) Describing Chakrabarty, the Court states that the modified bacterium was patentable because it was new with markedly different characteristics from any found in nature and one having potential for significant utility. (underlining added) Thus, discoveries that possess markedly different characteristics from any found in nature, are patentable, but any existing organism or newly discovered plant found in the wild is not patentable

24 CAFC Decision Roslin contends that the clones are the product of human ingenuity and not nature s handiwork, but [their] own. But Dolly does not possess markedly different characteristics from any [farm animals] found in nature. Dolly s genetic identity to her donor parent renders her unpatentable. Phenotypic differences due to epigenetic events do not help Roslin because they are unclaimed. Further, they do not require the hand of man to intervene and occur naturally.

25 CAFC Decision Roslin argues that they are structurally different at the cellular level due to differences in mitochondrial DNA. CAFC states that this is of no moment because this feature is also not claimed Nothing in the specification shows how mitochondrial differences might change the cloned mammals. BPAI said: [a]s for the influence of the oocyte into which the donor nucleus is transferred, the [ ]233 Specification teaches that [a]nimals produced by transfer of nuclei from a source of genetically identical cells share the same nucleus, but are not strictly identical as they are derived from different oocytes. The significance of this different origin is not clear, but may affect commercial traits. The Specification cautions further that [i]t remains... to consider whether it is possible or necessary in specific situations to consider the selection of oocytes. Thus... the Specification does not disclose any systematic differences in the clones that arise from the capture of the recipient oocyte.

26 Conclusions?