CLAIM  NOS:  HP-­2017-­000040,  HP-­2017-­000069  and  IL-­2017-­000016  
`IN  THE  HIGH  COURT  OF  JUSTICE  
`CHANCERY  DIVISION  
`PATENTS  COURT  
`B  E  T  W  E  E  N:  
`
`  
`(1)   SILENCE  THERAPEUTICS  GmbH  
`Claimant  in  the  SPC  action  /    
`Defendant  in  the  revocation  action  
`(2)   SILENCE  THERAPEUTICS  PLC  
`Defendant  in  the  revocation  action  
`
`-­  and  -­  
`
`(1)  ALNYLAM  UK  LIMITED  
`(2)  ALNYLAM  PHARMACEUTICALS  INC  
`(3)  THE  MEDICINES  COMPANY  UK  LIMITED  
`Defendants  in  the  SPC  action  /    
`Claimants  in  the  revocation  actions  
`  
`
`  
`DEFENDANTS’  SKELETON  ARGUMENT  FOR  THE  CMC  
`(Hearing  estimated  at  2  –  3  hours)  
`  
`
`Mark  Chacksfield  
`
`Michael  Conway  
`
`  
`
`Instructed  by  Potter  Clarkson  LLP  for  the  First  and  Second  Defendants  
`
`and  
`
`Bird  &  Bird  LLP  for  the  Third  Defendant  
`  
`
`1.  
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`Silence Therapeutics GMBH Exhibit 2001 Page 1
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`Suggested  pre-­reading  
`(estimate  2  hours)  
`
`The  Patent  (skim  for  flavour)  [A1]  
`
`Pleadings  –  Silence’s  SPC  declaratory  action  
`
`Particulars  of  Claim  [B1/2]  
`Alnylam’s  Defence  [B1/4]  
`[TMC’s  materially  similar  Defence  is  at  [B1/5]  but  need  not  be  read  separately]  
`
`  
`
`Alnylam’s  revocation  action  &  Silence’s  infringement  counterclaim  
`
`Particulars  of  Claim  [B1/8]  
`Grounds  of  Invalidity  [B1/11]  
`(the  prior  art  need  not  be  read,  but  for  reference  is  in  [B2,  parts  1  &  2])  
`Defence  and  Counterclaim  [B1/12]  
`Reply  and  Defence  to  Counterclaim  [B1/13]  
`[Note  also  the  materially  parallel  TMC’s  revocation  action  &  Silence’s  infringement  counterclaim  are  
`at  [B1/14  –  18]  but  need  not  be  considered  separately.]  
`
`Evidence  
`
`Morgan  2  [C1/5]  
`Nicholas  McDonald  2  [D1/7]  
`Morag  Macdonald  2  [D2/4]  
`Morag  Macdonald  3  [D2/9]  
`
`Excerpt  from  Alnylam’s  EPO  opposition  [attached  hereto]  
`
`Draft  consolidated  order  (with  opposing  positions  marked  up)  and  clean  version  [D2/10]  
`
`Introduction  and  issues  
`
`This  is  the  CMC  in  a  patent  action  concerning  so-­called  RNA  interference  (‘RNAi’).    The  
`patent  in  suit  (EP  (UK)  2,258,847,  ‘the  Patent’)  is  a  relatively  recently  granted  divisional  
`patent  based  on  a  filing  in  2003,  nearly  15  years  ago.  
`
`The  Patent  is  under  opposition,  the  9  month  window  having  recently  closed.    There  were  
`also  earlier  opposition  proceedings  against  the  grandparent  patent  (EP  1,527,176),  during  
`which  Silence  was  forced  to  abandon  its  initially  broad  claims  and  amend  down  to  a  very  
`restricted  narrow  set  of  features  which  are  not  said  to  be  of  any  commercial  relevance.    
`
`Finally  there  is  the  parent  patent  (EP  1,857,547,  the  ‘Parent’)  in  relation  to  which  the  EPO  
`has  recently  issued  a  decision  to  grant.    So  far  Silence  has  refused  to  state  its  intentions  
`with  respect  to  this  patent.  
`
`2.  
`
`1.  
`
`2.  
`
`3.  
`
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`Silence Therapeutics GMBH Exhibit 2001 Page 2
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`4.  
`
`5.  
`
`6.  
`
`7.  
`
`Used   as   a   therapy,   RNAi,   in   a   nutshell,   involves   taking   a   chunk   of   modified   RNA   and  
`introducing   it   into   a   patient,   where   it   interferes   with   expression   of   specific   undesirable  
`proteins.    It  is  a  complex  and  relatively  new  field,  based  upon  observations  in  nematode  
`worms   reported   in   Nature   in   1999   and   was   the   subject   of   the   2006   Nobel   Prize   for  
`Medicine.    It  is  not,  to  our  knowledge,  a  technology  that  has  previously  been  before  the  
`Court.  
`
`Silence   is   a   smallish   biotech   company.     Silence   describes   itself   as   a   ‘leader   in   the  
`discovery,   delivery   and   development   of   novel   RNA   therapeutics   for   the   treatment   of  
`serious  diseases  with  unmet  medical  needs’  and  states  that  ‘[its]  fundamental  chemical  
`modification   technology   is   a   core   foundational   innovation   for   today’s   RNAi   sector’ 1.    
`Despite  the  passage  of  15  years  since  the  priority  date  of  its  allegedly  foundational  Patent,  
`Silence  does  not  have  any  RNAi  projects  of  its  own  which  have  successfully  progressed  
`beyond  early  pre-­clinical  work2.    It  is  apparently  in  the  light  of  these  difficulties  that  Silence  
`has  sought  to  develop  a  business  model  as  a  patent  assertion  entity,  which  is  the  focus  of  
`these  proceedings.  
`
`Alnylam3  is  a  larger  US-­based  biotech  company  which  has  extensively  developed  RNAi  
`technology  and,  as  can  be  seen  from  the  evidence,  has  invested  heavily  in  R&D  directed  
`to  developing  RNAi  into  actual  therapeutic  candidates  including  an  extensive  programme  
`of  clinical  trials  (see  Nicholas  McDonald  1  &  2).  
`
`The   Medicines   Company   (‘TMC’),   in   collaboration   with   Alnylam,   has   also   been  
`developing  RNAi  therapeutic  products  as  a  class  of  medicines  and  in  particular  ‘inclisiran’.    
`TMC  has  made  and  is  continuing  to  make  a  substantial    investment  in  developing  inclisiran  
`(see  witness  statements  of  Morag  Macdonald  1  &  2).  
`
`8.  
`
`The  action  involves  three  claims:  
`
`i.  
`
`The   first   is   a   very   unusual   type   of   claim   for   declaratory   relief   of   a   kind   never  
`previously  brought  in  the  UK  nor  elsewhere4.    Silence  seeks  a  declaration  that  it  
`would  be  entitled  to  SPCs  for  the  Patent  based  on  Alnylam’s  and  TMC's  as  yet  un-­
`granted   (and   save   in   respect   of   patisiran,   yet   to   be   applied   for)   marketing  
`
`
`1  Morag  Macdonald  2  §19.  
`2  Morag  Macdonald  2  §19.  
`3  For  the  purposes  of  this  CMC  (but  without  any  admission  on  issues  of  substance),  there  is  no  need  to  
`distinguish  between  the  two  Alnylam  entities.  
`4  To  our  knowledge,  at  least.  
`
`
`
`3.  
`
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`authorisations,  on  the  footing  that  it  says  that  it  wants  to  claim  licence  fees  for  the  
`SPC  period5  (‘the  SPC  Declaration  Action);;  
`
`ii.  
`
`The  second  and  third  are  claims  for  the  revocation  of  the  Patent  and  declarations  of  
`non-­infringement,  respectively  by  Alnylam  and  TMC,  wherein  Silence  has  brought  
`counterclaims  for  infringement  (‘the  Patent  Actions’).  
`
`9.  
`
`The  SPC  Declaration  Action  was  issued  in  July  2017.    At  Silence’s  insistence,  and  upon  
`its  application,  the  three  actions  have  already  been  set  down  to  be  heard  from  the  first  
`available  date  on  or  after  3  December  2018.    The  trial  is  estimated  to  require  10  days  of  
`Court  time,  and  additionally  2  days  of  pre-­reading.    The  technical  difficulty  rating  is  agreed  
`to  be  5.      
`
`10.   The   claims   are   each   valued   at   in   excess   of   £10M,   and   the   products   themselves   are  
`predicted  by  third  party  analysts  to  achieve  total  sales  until  the  end  of  2028  (the  date  when  
`any  SPC  will  expire)  of  around  $60  billion6.    Silence  has  previously  stated  that  its  claims  
`for  royalties  could  reach  “hundreds  of  millions  of  pounds”7.    On  any  basis  this  is  amongst  
`the  very  heaviest  of  biotech  litigation.  
`
`The  Products  
`
`11.   There  are  four  different  products  in  issue  at  different  stages  of  development.    Each  of  them  
`has  the  potential  to  offer  important  therapies  to  patients  in  areas  of  unmet  or  insufficiently  
`met  clinical  need:  
`
`i.  
`
`Patisiran   is   an   investigational   RNAi   therapeutic   targeting   transthyretin   (TTR)   in  
`development  for  the  treatment  of  hereditary  ATTR  amyloidosis  (hATTR  amyloidosis)  
`–  a  genetic  disease  affecting  approximately  50,000  patients  worldwide,  with  limited  
`treatment  options.    
`
`ii.  
`
`Fitusiran   is   an   investigational   RNAi   therapeutic   targeting   antithrombin   (AT)   in  
`development  for  the  treatment  of  haemophilia  and  rare  bleeding  disorders.    
`
`iii.   Givosiran   is   an   investigational   RNAi   therapeutic   targeting   aminolevulinic   acid  
`synthase  1  (ALAS1)  for  the  treatment  of  acute  hepatic  porphyrias  (AHPs).    
`
`
`5  More  particularly  that  the  four  products  are  protected  by  the  Patent  within  the  meaning  of  Art  3(a)  of  the  
`SPC  Regulation,  and  that  any  MA  granted  would  be  a  valid  authorisation  within  the  meaning  of  Art  3(b).  
`6  Nicholas  McDonald  2  §8.  
`7  [B1/9].  
`
`
`
`4.  
`
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`iv.  
`
`Inclisiran  is  an  investigational  RNAi  therapeutic  being  developed  by  TMC  for  the  
`treatment  of  hypercholesterolemia.    
`
`Issues  in  the  case  
`
`12.   The  claims  are  at  p.110-­111  of  the  Patent  [A1].    Claims  1  –  6,  8  –  10  and  13  of  the  Patent  
`are  asserted.    Claim  1  reads:  
`
`13.  
`
`Infringement  is  disputed,  and  the  basis  for  Silence’s  assertion  of  infringement  is  far  from  
`clear  and  to  date  has  not  been  explained.    For  example,  the  structure  of  patisiran  (likely  
`the  first  of  the  products  to  obtain  an  MA)  is  set  out  in  Alnylam’s  opposition  to  the  Patent  
`as  follows:    
`
`  
`
`  
`
`14.  
`
`It  is  admitted  that  not  all  of  the  claims  are  entitled  to  priority,  and  validity  is  attacked  for  
`lack  of  novelty,  obviousness  and  insufficiency.  
`
`15.   The  insufficiency  plea  is  of  particular  relevance  to  the  issues  on  this  CMC,  and  the  Court  
`is   invited   to   read   sections   9.2   –   9.4   of   Alnylam’s   Notice   of   Opposition   to   the   Patent  
`[attached  hereto],  which  are  directed  to  scope  of  claim  under  obviousness  in  the  AgrEvo  
`sense  (Art  56)  and  insufficiency  (Art  83)  for  a  flavour  of  some  of  the  arguments.  
`
`16.   There  are  additionally  issues  arising  out  of  Silence’s  claim  to  declaratory  relief,  and  as  to  
`the  meaning  and  scope  of  Arts  3(a)  and  3(b)  of  the  SPC  Regulation.  
`
`
`
`5.  
`
`Silence Therapeutics GMBH Exhibit 2001 Page 5
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`The  Issues  on  the  CMC  
`
`17.   Subject  to  the  Court’s  approval  of  the  agreed  provisions,  the  following  matters  remain  in  
`issue:  
`
`i.  
`
`ii.  
`
`Disclosure  in  relation  to  insufficiency;;  
`
`Deadlines  for  fact  evidence;;  
`
`iii.  
`
`The  number  of  expert  witnesses;;  
`
`iv.   Clarification  of  Silence’s  position  on  the  Parent  Patent;;  
`
`v.  
`
`A  few  remaining  disputes  on  the  dates  for  specific  steps.  
`
`Disclosure  
`
`18.   The  parties  have  filed  disclosure  statements  [B1/6,  21,  and  22].    That  of  Silence  is  directed  
`only  to  its  SPC  claim,  and  not  to  the  Patent  Actions.  
`
`19.   The   parties   are   agreed   that   Alnylam   and   TMC   should   between   them   provide   product  
`descriptions  addressed  to  the  four  products.  
`
`20.   No  disclosure  is  sought  as  regards  obviousness.    The  issue  between  the  parties  concerns  
`disclosure  relating  to  insufficiency.  
`
`21.   This  is  a  case  in  which  insufficiency  is,  as  the  Court  will  appreciate  from  the  pleadings  and  
`the  gist  of  the  opposition  submissions,  a  substantive  and  substantial  one  –  it  is  not  just  a  
`‘sheep  dog’  as  is  sometimes  the  case.    The  allegation  that  the  teaching  of  the  Patent  is  
`not  sufficient  to  support  claims  of  the  breadth  that  Silence  appears  to  advance  is  plainly  a  
`real  one  which  will  require  serious  investigation  at  trial,  and  one  of  the  core  issues  is  this:  
`do  the  oligonucleotides  as  parameterised  within  the  claims  actually  work?  
`
`22.   This  raises  a  straight  issue  of  fact  –  which  of  the  modified  oligonucleotides  are  stable  and  
`effective?     That   is   something   that   is   likely   not   readily   answerable   from   the   published  
`papers,   since   rarely   if   ever   do   companies   publicise   failures,   but   it   is   material   that   the  
`parties  have  in  their  possession  which  can  readily  be  produced8.  
`
`23.   Alnylam  and  TMC,  in  the  course  of  R&D  work,  have  between  them  made  and  tested  many  
`different   modified   potential   RNAi   products,   in   the   course   of   which   testing   they   have  
`
`
`8  Morag  Macdonald  3  §5.  
`
`
`
`6.  
`
`Silence Therapeutics GMBH Exhibit 2001 Page 6
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`encountered  many  difficulties,  failures  and  dead  end  potential  products.    The  identification  
`of  the  oligonucleotides  tested,  and  the  results  of  the  tests  performed  on  them,  is  highly  
`relevant  to  the  question  of  whether  and  to  what  extent  the  claims  encompass  inoperative  
`subject  matter9.      
`
`24.   Alnylam  and  TMC  intend  to  adduce  fact  evidence  at  trial  about  this,  and,  if  ordered,  to  
`provide  the  appropriate  disclosure.  
`
`25.   Mr  Morgan  questions  whether  the  disclosure  from  Silence  would  be  useful10.    But  given  its  
`15  years  of  work,  without  any  real  progress,  the  inference  is  that  Silence  has  carried  out  
`research   into   a   variety   of   RNAi   therapeutic   targets   and   presumably   researched   the  
`modification  of  a  range  of  siRNAs  for  this  purpose  which  have  not  in  fact  proved  stable  
`and  efficacious,  despite  their  knowledge  at  least  of  what  is  disclosed  in  the  Patent11.  
`
`26.   Alnylam   and   TMC   have   written   to   Silence   requesting   that   it   clarify   whether   or   not   it  
`proposes  to  advance  any  positive  case  at  trial  on  insufficiency  based  upon  or  by  reference  
`to  any  RNAi  molecules  produced  or  tested  by  it  or  its  licensees  (whether  developed  in  
`factual  evidence,  via  expert  evidence  or  through  materials  or  questions  put  to  any  witness  
`at  trial)12.    This  is  a  letter  to  which  Silence  has  failed  to  respond,  despite  being  chased.  
`
`27.   One  can  understand,  tactically,  why  Silence  refuses  to  do  so.    It  wishes  to  keep  open  the  
`option  of  adducing  such  evidence  without  stating  this  now,  since  stating  this  now  would  
`have  obvious  disclosure  ramifications.  
`
`28.   Silence  should  not,  however,  be  allowed  to  duck  the  issue  in  this  way,  and  should  make  
`clear  at  the  CMC  whether  or  not  it  will  advance  any  such  case  at  trial.    If  it  will  not  make  
`its  position  plain,  then  a  timetable  for  it  to  do  so  should  be  provided,  as  per  paragraph  9.2  
`of  Alnylam  and  TMC’s  updated  draft  order  (see  Exhibit  MXM-­7  to  Morag  Macdonald  3).  
`
`
`9  Or,  if  said  to  be  functionally  limited,  are  clearly  defined.  
`10  Morgan  2  §§16-­19.  
`11  Morag   Macdonald   2   §32.   The   Defendants’   position   in   this   regard   is   also   supported   by   the   learned  
`editors  of  Terrell,  who  state  that  “In  contrast  to  the  position  on  obviousness,  disclosure  going  to  pleaded  
`insufficiency  allegations  is  generally  more  readily  ordered.  It  can  be  powerful  evidence  in  support  of  an  
`insufficiency  if  the  patentee’s  own  documents  show  that  despite  serious  efforts  to  do  so,  they  were  unable  
`to  work  the  claimed  invention,  either  at  all  or  in  some  material  respect.  Similarly,  attempts  of  the  party  
`alleging  insufficiency  will  be  equally  relevant.”  –  Terrell  on  Law  of  Patents,  (18th  Edn.  Sweet  &  Maxwell  
`2016)  at  19-­295.  
`12  Morag  Macdonald  3  §8.  
`
`
`
`7.  
`
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`

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`29.  
`
`If  Silence  chooses  not  to  run  a  case  based  upon  or  by  reference  to  its  (or  its  licensees)  
`work,  then  Alnylam  and  TMC  are  more  sanguine  about  the  disclosure  issue,  and  will  not  
`press  for  it13.  
`
`30.  
`
`If,  however,  Silence  is  to  run  such  a  case  then  it  should  give  appropriate  disclosure.    The  
`question  is  then  just  one  of  what  is  appropriate,  in  all  the  circumstances14.      
`
`31.   This  is  of  course  a  case  of  the  highest  value,  and  complexity.    Third  parties  put  the  total  
`aggregate  sales  up  to  202815  of  the  four  products  in  the  region  of  $60  billion.    Silence  has  
`proclaimed  that  it  seeks  royalties  in  the  “hundreds  of  millions”,  and  whilst  it  will  no  doubt  
`seek  to  retreat  from  those  figures  at  the  hearing  by  reference  to  the  local  nature  of  this  
`action,  the  reality  is  that  it  is  trying  to  use  this  jurisdiction  as  a  testing  bed  for  the  totality  of  
`its  royalty  claim.  
`
`32.  
`
`It  is  also  an  action  with  a  wider  public  interest,  relating  as  it  does  not  only  to  a  public  
`monopoly  right,  but  a  monopoly  right  which  Silence  has  threatened  to  try  to  use  to  prevent  
`the  marketing  by  Alnylam  and  TMC  of  the  four  products16,  each  of  which  is  directed  to  
`treating  areas  of  unmet  or  insufficiently  met  clinical  need.      
`
`33.   Mr  Morgan’s  evidence  is  that  the  disclosure  exercise  would  be  expensive.    He  quotes  a  
`figure  of  £1.5M,  although  the  explanation  of  this  in  his  evidence  is  most  unclear.  Given  
`that   this   figure   is   10   times   the   costs   anticipated   by   Alnylam,   a   company   which   is  
`substantially  larger  and  which  has  successfully  taken  four  products  into  advanced  stages  
`of  development,  one  would  have  expected  a  much  more  detailed  explanation  to  support  
`these  figures.  
`
`34.   Furthermore  Ms  Macdonald  is  surprised  by  these  numbers,  and  in  her  experience  puts  
`the  normal  costs  of  a  disclosure  search  even  of  the  scope  described  at  about  a  fifth  of  that  
`figure.    She  does  not  understand  why  this  exercise  would  cost  the  sorts  of  sums  that  Mr  
`Morgan  suggests,  and  he  does  not  provide  any  detail  to  explain  the  figures  he  advances.  
`See  Macdonald  3  §§10  –  12  [D2/9].      
`
`35.   Lastly  Mr  Morgan  notably  fails  to  make  any  counter  suggestion  that  would  be,  in  his  view,  
`proportionate  to  the  matters  which  are  in  issue  in  this  case;;  a  case  which  Silence  seeks  to  
`
`
`13  Reserving  their  rights  to  draw  inferences  in  due  course.  
`14  CPR   31.5(7)   and   the   overriding   objective   are   germane   here,   in   particular   so   as   to   achieve   justice  
`between  the  parties  having  regard  inter  alia  to  the  value  and  importance  of  the  case  to  the  parties,  equality  
`of  arms,  the  relevance  of  the  documents  sought  and  the  costs  of  the  exercise.  
`15  The  end  of  any  potential  SPC  period.  
`16  E.g.  Morgan  1  §30  [C1/1].  
`
`
`
`8.  
`
`Silence Therapeutics GMBH Exhibit 2001 Page 8
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`

`

`use  to  extract  royalties  it  puts  in  the  hundreds  of  millions.    Where  a  party  brings  a  case  to  
`Court,  and  intends  to  rely  on  its  own  internal  work  to  support  it,  it  is  not  good  enough  for  it  
`just  to  say  “the  disclosure  you  propose  is  too  much  so  you  can’t  have  anything”.    Only  
`Silence  has  knowledge  of  the  nature  of  the  documents  in  its  possession  after  all17.    In  
`particular  it  is  not  clear  whether  all  of  the  potential  documents  he  refers  to  actually  relate  
`to   the   core   issue   of   the   identities   of   modified   oligonucleotides   tested   for   stability   and  
`efficacy  in  vitro  and  in  vivo,  and  the  results  of  those  tests,  nor  does  he  indicate  a  different  
`search  that  would  capture  the  relevant  material  in  a  more  cost-­effective  manner.      
`
`36.   As  regards  the  suggestion  of  a  PDD,  this  was  proposed  so  as  to  facilitate  the  parties’,  and  
`the   Court’s,   understanding   of   the   documents   disclosed.     The   proposal   was   purely   a  
`practical  one,  intended  to  reduce  costs  overall.    Given  Mr  Morgan’s  suggestion  that  the  
`costs  of  this  would  extend  to  £3M  (a  figure  that,  we  submit,  indicates  more  about  Silence’s  
`approach  to  estimating  costs  than  anything  else),  then  Alnylam  and  TMC  are  not  going  to  
`press  the  point.  
`
`37.   As  regards  the  SPC  claim,  both  sides  may  wish  to  adduce  fact  evidence  relating  to  the  
`pleaded  issues,  but  are  content  to  progress  this  part  of  the  case  without  disclosure  on  
`either  side.    
`
`Deadlines  for  fact  evidence  and  CEA  notices  
`
`38.   There  is  a  dispute  over  the  deadline  for  the  parties  to  serve  fact  evidence.    Silence  seeks  
`a  date  in  line  with  the  expert  evidence:  14  September  2018  for  evidence  in  chief  and  replies  
`on   26   October   2018.    Alnylam   and   TMC   consider   this   unworkable.     It   is   likely   that  
`substantial  aspects  of  the  fact  evidence  will  be  material  to  which  the  experts  will  need  to  
`have  reference  when  preparing  their  reports  –  insufficiency  for  example.    Fact  evidence  
`therefore  needs  to  come  properly  in  advance  of  the  expert  reports.  
`
`39.   The  only  reason  Silence  has  given  for  its  proposed  dates  is  the  inconvenience  that  it  says  
`would   be   involved   in   requiring   the   parties   to   serve   fact   evidence   during   the   summer  
`vacation  period.18    As  it  is,  however,  Alnylam  and  TMC  now  propose  that  fact  evidence  be  
`exchanged  on  31  May  for  evidence  in  chief  and  28  June  for  any  reply  evidence.    These  
`dates  are  suggested  to  ensure  that  there  is  proper  time  between  the  service  of  fact  and  
`expert  evidence,  but  have  the  happy  coincidence  of  dealing  with  Mr  Morgan’s  summer  
`vacation  point.  
`
`
`17  And  this  is  not  helped  by  Silence’s  failure  to  provide  a  disclosure  report  relating  to  the  Patent  Actions.  
`18  Morgan  2  §38.  
`
`
`
`9.  
`
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`

`40.   CEA  notices  should  be  filed  with  fact  evidence  in  chief,  since  after  all  that  is  what  they  are.  
`
`The  number  of  expert  witnesses  
`
`41.   The  Patent  relates  to  the  therapeutic  use  of  modified  oligonucleotides  in  RNAi.    Alnylam  
`and   TMC   wish   to   call   two   experts   (they   agree   that   it   is   appropriate   for   them   to   share  
`experts):  one  in  RNAi  technology  and  one  in  oligonucleotide  therapeutics,  reflecting  the  
`underlying  issues.  
`
`42.   Silence  disagrees  and  says  that  only  one  expert  witness  is  necessary  on  each  side,  in  the  
`field  of  oligonucleotide  therapeutics.  
`
`43.   The  evidence  of  Ms  Macdonald,  based  on  her  investigations  of  the  field  to  date,  is  that  
`typically  no  one  individual  is  expert  in  both  the  chemistry  relating  to  oligonucleotides  and  
`the  therapeutic  application  of  RNA  interference  technology.    As  such  Silence’s  proposal  is  
`unrealistic  or  unworkable.      
`
`44.   Mr  Morgan  cites  the  increased  costs  of  having  two  experts,  but  that  must  be  considered  
`in  the  context  of  litigation  of  this  value  and  complexity.    As  Ms  Macdonald  notes  in  her  
`evidence,   it   is   not   uncommon   that   more   than   one   expert   will   be   instructed   in  
`biopharmaceutical  cases  involving  issues  of  both  the  underlying  science  and  therapeutic  
`application19,  and  there  is  a  need  for  such  here.      
`
`Clarification  of  Silence’s  position  on  the  Parent  Patent  
`
`45.   Shortly   before   Christmas   the   EPO   issued   a   decision   to   grant   the   Parent   Patent.     The  
`expected   date   for   mention   of   the   grant   is   17   January   2018.     The   Defendants   have  
`separately  written  to  Silence  requesting  that  it  state  its  intentions  in  relation  to  the  Parent  
`Patent.    It  must  know  its  plans,  since  this  patent  has  been  15  years  in  the  writing,  and  no  
`doubt  has  been  crafted  with  its  patent  assertion  business  in  mind.    But  thus  far  Silence  
`has  failed  to  respond  substantively.20    
`
`46.   The  Parent  Patent  and  the  Patent  derive  from  the  same  application,  and  are  very  closely  
`related.    If  Silence  intends  to  make  any  claim  in  respect  of  the  Parent  Patent,  whether  for  
`infringement  and/or  for  some  kind  of  declaratory  relief  (if  available),  then  it  is  self-­evidently  
`desirable  that  it  should  do  so  within  the  present  proceedings.      
`
`
`19  Macdonald  2  §38.  
`20  CMS  second  letter  of  8  January  2017.  
`
`
`
`10.  
`
`Silence Therapeutics GMBH Exhibit 2001 Page 10
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`

`47.  
`
`It  would  have  been  helpful  had  Silence  chosen  to  indicate  its  intentions  in  advance  of  the  
`CMC,  but  its  position  has  instead  been  tactical  and  remains  unknown21.    This  game  playing  
`should  stop,  and  if  it  is  not  willing  to  break  its  silence  at  the  CMC  then  Silence  should  be  
`required  to  state  its  position  within  a  reasonable  period  thereafter  –  by  28  February  2018  
`is  proposed.    
`
`Miscellaneous  dates  
`
`48.   There  are  a  number  of  other  dates  on  which  the  parties  have  yet  to  agree,  namely:  
`
`i.  
`
`ii.  
`
`Notices  to  Admit  Facts;;  
`
`Notification  of  independently  valid  claims;;  
`
`iii.   Date  for  nominating  experts;;  
`
`iv.   Service  of  expert  reports  in  chief  and  in  reply.  
`
`49.   The   first   two   have   a   little   substance.     Silence   proposes   1   June   and   13   April   2018  
`respectively.    These  are  too  late.    In  general,  and  in  litigation  of  this  weight  in  particular,  
`the  parties  should  deal  with  matters  promptly  and  up  front.    This  is  litigation  of  Silence’s  
`bringing,  and  it  is  they  who  forced  an  early  application  for  a  trial  date  on  Alnylam  and  TMC.    
`There   is   no   reason   to   delay   getting   on   with   matters.   Alnylam   and   TMC   suggest   14  
`February  2018  and  28  February  2018  respectively.  
`
`50.   The  remaining  dates  appear  minor  points,  which  it  is  hoped  can  be  agreed,  and  if  not  
`should  not  take  long  to  address  orally.      
`
`
`21  See  CMS’  second  letter  of  8  January  2017.  
`
`
`
`11.  
`
`Silence Therapeutics GMBH Exhibit 2001 Page 11
`
`