EFTA00748858Set 9
159p42,676w
Finite population size 69
4.6 Numerical simulations 75
4.7 General Payoff Matrix 76
5 Mutation—selection equilibrium in games with multiple strategies 86
5.1 Introduction 86
5.2 Perturbation method ... Special case: Two strategies 97
5.2.2 Low mutation rates 97
5.3 Examples 99
5.3.1 Cooperators, Defectors, Loners 99
5.3.2 Reversing the ranking of strategies by mutation 101
5.3.3 Cooperators, Defectors ... Outlook 106
5.4.1 Strong selection 106
5.4.2 More general mutation rates 107
5.4.3 Alternative processes 108
5.5 Discussion 110
6 Mutation-selection equilibrium in games with mixed strategies
https://www.justice.gov/epstein/files/DataSet%209/EFTA00748858.pdf
EFTA00603737Set 9
17p11,455w
result of colorectal epithelium) and travelled through the circulation until it
the mutations that occur during each cell division. What is remark- lodged at a distant site (for example, lung ... cell within a the metastatic lesion is assumed to have all the driver gene mutations
large tumour often contains the same core set of genetic altera- needed to expand. Motivated ... histopathological images (Fig. la), we
tions, with heterogeneity confined to mutations that emerge late model the lesion as a conglomerate of balls of cells (see Methods and
during tumour growth
https://www.justice.gov/epstein/files/DataSet%209/EFTA00603737.pdf
EFTA01201684Set 9
2010-10-087p6,726w
Timing and heterogeneity of mutations associated with
drug resistance in metastatic cancers
Ivana Bozic'' and Martin A. Nowa ka'bi
'Program for Evolutionary Dynamics, Department of Mathematics, and °Department ... cancer therapy were concerned with calculating the proba-
resistance have been implicated, including mutation of target bility that cells resistant to chemotherapy are present in a tumor
genes and activation ... advantage or disadvantage
preexisting subpopulation of resistant cells; however, little is provided by resistance mutations (17, 18), multiple mutations
known about the genetic composition of this resistant subpopu• needed
https://www.justice.gov/epstein/files/DataSet%209/EFTA01201684.pdf
EFTA01140242Set 9
2013-08-2714p12,142w
found in Human
for the adoption of this technology into medical practice. We Genome Mutation Database (HGMD) (13, 14) and labeled
performed whole exome sequencing (WES) on 81 volunteers ... disease-causing mutations (DM). These alleles also were re-
for each volunteer, we requested personal medical histories, quired to be rare (<1% allele frequency in 6,500 exomes from
constructed ... only rare Genomes (16, 17)] and predicted to be damaging to protein
damaging mutations and known pathogenic variations in genes function by two of three predictions algorithms [Polyphen 2.0
previously
https://www.justice.gov/epstein/files/DataSet%209/EFTA01140242.pdf
EFTA01100261Set 9
2016-02-2939p20,086w
wide variety of diseases with over 6,000 diseases caused by a genetic
mutation and 95% having no approved therapy. Key targets include muscular dystrophy, cystic fibrosis, various
malignant ... allow Editas to perform gene editing
through various methodologies to address most disease-causing mutations.
Exhibit 12: Approaches Available to Gene Editing for Editas
CUT & REVISE CUT & REMOVE CUT & REPLACE ... hods for selenms specific cells by
2,734,162 introducing precru, mutations utplung the CRISell
Cas system
Source: EPO org. Morgan Stanley Research
Nine oppositions have been filed against Patent
https://www.justice.gov/epstein/files/DataSet%209/EFTA01100261.pdf
second problem is that many cancer cells,
responding to a prevention drug, can quickly mutate to become immune and more resilient.
Due to recent advances in circulating tumor cell technology ... cancer. To date, the test has
identified more than 1,200 cancer-causing genetic mutations, the largest collection in the world. The
findings have led to a host of cancer ... genotype-directed clinical trial. The test can also help identify the specific mutation within
the cell that makes it cancerous. "Even though a cancer cell may have hundreds of mutations
https://www.justice.gov/epstein/files/DataSet%209/EFTA01085311.pdf
EFTA02443859Set 11
12p5,813w
Arnold, R Burger (2003). Stability of the G-matrix in a population
experiencing pleiotropic mutation, stabilizing selection, and genetic drift. Evolution 57: 1747-
1760.
6. Komarova NL, MA Nowak ... Kirby. Oxford University Press, 317-337.
8. Komarova NL, A Sengupta, MA Nowak (2003). Mutation-selection networks of cancer
initiation: Tumor suppressor genes and chromosomal instability. J theor Biol ... colorectal cancer. Nat Rev Cancer 3: 695-701.
16. Sasaki A, MA Nowak (2003). Mutation landscapes. J theor Biol 224: 241-247.
17. Wei X, JM Decker, S Wang
https://www.justice.gov/epstein/files/DataSet%2011/EFTA02443859.pdf
working, the CTC-
iChip's new ability to extract thousands of cancer cells for mutation analysis will allow
patients to have a far more tailored and less toxic treatment ... targeting only those
mutations that are causing the cancer. Today, this is done with drugs that block a
pathway unique to a mutated cell's surface, or in the field ... kidney or its base. Each cell type typically has a variety of genetic mutations. For
example, non-small cell lung cancer cells have about three known mutation types
https://www.justice.gov/epstein/files/DataSet%2011/EFTA02714314.pdf
EFTA00611781Set 9
2013-12-137p6,384w
what is the time scale required population of size N, which reproduces asexually. The mutation
by evolution to discover the sequences that perform desired rate, u, is small: individual mutations ... given length are arranged such that distance one.
nearest neighbors differ by one point mutation [19]. For constant
selection, each point in sequence space is associated with a non-
Results ... explores a succeeded, if the population discovers a sequence that differs
fitness landscape. The mutation-selection process biases from the specific sequence in no more than a fraction
https://www.justice.gov/epstein/files/DataSet%209/EFTA00611781.pdf
EFTA00760692Set 9
302p12,726w
Arnold, R Burger (2003). Stability of the G-matrix in a
population experiencing pleiotropic mutation, stabilizing selection, and
genetic drift. Evolution 57: 1747-1760.
NL, MA Nowak (2003). Language dynamics ... Christiansen, S Kirby. Oxford University
Press, 317-337.
NL, A Sengupta, MA Nowak (2003). Mutation-selection networks of
cancer initiation: Tumor suppressor genes and chromosomal instability. J
theor Biol ... colorectal cancer. Nat Rev Cancer 3: 695-701.
Sasaki A, MA Nowak (2003). Mutation landscapes. J theor Biol 224: 241-247.
Wei X, JM Decker, S Wang
https://www.justice.gov/epstein/files/DataSet%209/EFTA00760692.pdf
EFTA00583237Set 9
3p1,238w
Final Frontier? Inhibitor Cocktails to Stamp out Cancer
The use of mutation-specific, inhibitor drugs to fight cancer has been growing in popularity around the world. In
fact, over ... enzyme pathway found
distinctly on breast cancer cells with a BRAC genetic mutation. The PARP molecule's attachment prevents the cell
from performing DNA repair, leading to its death.
What ... become immune to an inhibitor drug. Their
models also showed how even a single mutated cell can quickly evolve to tumor level. For example, approximately
half of non-small cell
https://www.justice.gov/epstein/files/DataSet%209/EFTA00583237.pdf
EFTA01177305Set 9
3p1,238w
Final Frontier? Inhibitor Cocktails to Stamp out Cancer
The use of mutation-specific, inhibitor drugs to fight cancer has been growing in popularity around the world. In
fact, over ... enzyme pathway found
distinctly on breast cancer cells with a BRAC genetic mutation. The PARP molecule's attachment prevents the cell
from performing DNA repair, leading to its death.
What ... become immune to an inhibitor drug. Their
models also showed how even a single mutated cell can quickly evolve to tumor level. For example, approximately
half of non-small cell
https://www.justice.gov/epstein/files/DataSet%209/EFTA01177305.pdf
EFTA00803978Set 9
2018-10-166p6,713w
example, when a leading-eight donor is picked at random. With probability p (the mutation rate),
defects against an ALLC recipient, who is mistakenly considered this player then adopts some ... Overall, the two modes of
population member can have considerable consequences on the updating, mutation and imitation, give rise to an ergodic process
further reputation dynamics. on the space ... better understanding of such cases, we analytically we present results for the case when mutations are relatively
explored the consequences of a single disagreement in a homo- rare
https://www.justice.gov/epstein/files/DataSet%209/EFTA00803978.pdf
EFTA00611788Set 9
2013-12-137p6,378w
what is the time scale required population of size N, which reproduces asexually. The mutation
by evolution to discover the sequences that perform desired rate, el, is small: individual mutations ... given length are arranged such that distance one.
nearest neighbors differ by one point mutation [19]. For constant
selection, each point in sequence space is associated with a non-
Results ... explores a succeeded, if the population discovers a sequence that differs
fitness landscape. The mutation-selection process biases from the specific sequence in no more than a fraction
https://www.justice.gov/epstein/files/DataSet%209/EFTA00611788.pdf