Filed on behalf of: Junior Party, Broad

By:
Steven R. Trybus
Harry J. Roper
Jenner & Block LLP
353 North Clark Street, Chicago, IL 60654
Telephone: 312-222-9350
Facsimile: 312-527-0484
strybus@jenner.com

Paper No. ____

UNITED STATES PATENT AND TRADEMARK OFFICE

____________________
BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________________
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF
TECHNOLOGY, and PRESIDENT AND FELLOWS OF HARVARD COLLEGE,
Patents 8,697,359; 8,771,945; 8,795,965; 8,865,406; 8,871,445; 8,889,356; 8,895,308;
8,906,616; 8,932,814; 8,945,839; 8,993,233; and 8,999,641,
Junior Party,
v.
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, UNIVERSITY
OF VIENNA, and EMMANUELLE CHARPENTIER
Application 13/842,859,
Senior Party.

Patent Interference No. 106,048 (DK)

BROAD LIST OF PROPOSED MOTIONS

BROAD LIST OF PROPOSED MOTIONS

Pursuant to Part D of the Declaration of Interference (Paper No. 1), 37 C.F.R. 41.120

and 204, and 104.21, 120, and 204 of the Standing Order (Paper No. 2), Party Broad hereby

provides the following list of proposed motions (starting with motion 2 because Broad filed

Broad Miscellaneous Motion 1 (for substitution of lead and back-up counsel), Paper No. 25 on

March 2, 2016) that Broad presently requests permission to file:

I.

8
9

Threshold Motions
A motion under 37 C.F.R. 41.121(a)(1)(iii) and 208 (a)(1) on the ground that there is

no interference-in-fact between claims 165-200, 202-218, 220-222, and 224-247 (UCs

10

Involved Claims) of the involved application of The Regents of the University of California

11

(UCB), University of Vienna (Vienna) and Emmanuelle Charpentier (EC), (for

12

convenience, collectively referenced as UC), U.S. Patent Application No. 13/842,859 (the

13

859 application) and the claims of the involved Broad patents, each individually as set forth

14

below (for convenience, collectively, Broads Involved Claims):

15

2.

claims 1-20 of Broads involved U.S. Patent 8,697,359 (the 359 patent),

16

3.

claims 1-29 of Broads involved U.S. Patent 8,771,945 (the 945 patent),

17

4.

claims 1-30 of Broads involved U.S. Patent 8,795,965 (the 965 patent),

18

5.

claims 1-30 of Broads involved U.S. Patent 8,865,406 (the 406 patent),

19

6.

claims 1-30 of Broads involved U.S. Patent 8,871,445 (the 445 patent),

20

7.

claims 1-30 of Broads involved U.S. Patent 8,889,356 (the 356 patent),

21

8.

claims 1-30 of Broads involved U.S. Patent 8,895,308 (the 308 patent),

22

9.

claims 1-30 of Broads involved U.S. Patent 8,906,616 (the 616 patent),

23

10.

claims 1-30 of Broads involved U.S. Patent 8,932,814 (the 814 patent),

11.

claims 1-28 of Broads involved U.S. Patent 8,945,839 (the 839 patent),

12.

claims 1-43 of Broads involved U.S. Patent 8,993,233 (the 233 patent), and

13.

claims 1-28 of Broads involved U.S. Patent 8,999,641 (the 641 patent).

UCs Involved Claims, if treated as prior art, do not anticipate or render obvious Broads

Involved Claims, all of which limit the claimed CRISPR-Cas9 systems and methods to use in

eukaryotic cells as opposed to UCs Involved Claims, which are not so limited. Further, Broads

Involved Claims recite additional distinguishing features such as those set forth in Section IV

below. Thus, there is no interference-in-fact, pending any potential and currently unknown claim

construction arguments that UC may raise and the Board may adopt. Broad respectfully submits

10

that this motion raises a threshold issue and Broad respectfully requests that additional pages be

11

authorized due to the large number of Broad Involved Claims or alternatively that these be

12

authorized as separate motions with Broad authorized to cross-reference arguments between the

13

motions. 37 C.F.R. 41.201.

14

II.

15
16

Motions for Priority Benefit

Motions under 37 C.F.R. 41.121(a)(1)(ii) and 41.208(a)(3) establishing that Broad is

entitled to benefit of the following applications with respect to the subject matter of Count 1:

17

14.

61/736,527 filed on December 12, 2012 (B1) (in the priority chain of all of

18

Broads Involved Patents),

19

15.

20

Involved Patents),

21

16.

61/758,468 filed on January 30, 2013 (B3),

22

17.

61/768,959 filed on February 25, 2013 (B4),

23

18.

61/769,046 filed on February 25, 2013 (B5),

61/748,427 filed on January 2, 2013 (B2) (in the priority chain of all of Broads

19.

61/791,409 filed on March 15, 2013 (B6) (in the priority chain of all of Broads

Involved Patents),

20.

61/802,174 filed on March 15, 2013 (B7),

21.

61/806,375 filed on March 28, 2013 (B8),

22.

61/814,263 filed on April 20, 2013 (B9),

23.

61/819,803 filed on May 6, 2013 (B10),

24.

61/828,130 filed on May 28, 2013 (B11),

25.

61/835,931 filed on June 17, 2013 (B12) (in the priority chain of all of Broads

Involved Patents),

10

26.

61/835,936 filed on June 17, 2013 (B13),

11

27.

61/836,101 filed on June 17, 2013 (B14),

12

28.

61/836,127 filed on June 17, 2013 (B15),

13

29.

61/842,322 filed on July 2, 2013 (B16),

14

30.

14/054,414 filed on October 15, 2013 (B17) (issued as Involved 359 patent),

15

31.

14/104,977 filed on December 12, 2013 (B18),

16

32.

14/104,990 filed on December 12, 2013 (B19),

17

33.

14/105,017 filed on December 12, 2013 (B20) (issued as Involved 233 patent),

18

34.

14/105,031 filed on December 12, 2013 (B21),

19

35.

14/105,035 filed on December 12, 2013 (B22),

20

36.

PCT/2013/074736 filed on December 12, 2013 (B23),

21

37.

14/183,429 filed on February 18, 2014 (B24) (issued as Involved 945 patent),

22

38.

14/183,486 filed on February 18, 2014 (B25) (issued as Involved 965 patent),

23

39.

14/183,471 filed on February 18, 2014 (B26) (issued as Involved 356 patent),

40.

14/222,930 filed on March 24, 2014 (B27) (issued as Involved 406 patent),

41.

14/226,274 filed on March 26, 2014 (B28) (issued as Involved 641 patent),

42.

14/256,912 filed on April 18, 2014 (B29) (issued as Involved 839 patent),

43.

14/258,458 filed on April 22, 2014 (B30) (issued as Involved 814 patent),

44.

14/259,420 filed on April 23, 2014 (B31) (issued as Involved 420 patent),

45.

14/290,575 filed on May 29, 2014 (B32) (issued as Involved 616 patent), and

46.

14/293,498 filed on June 2, 2014 (B33) (issued as Involved 308 patent).

For completeness, the list includes the priority applications included in one or more of the

priority chains of the 12 Broad Involved Patents including the 12 applications that issued as

10

Broad Involved Patents. Broad recognizes that it may not need to brief the entirety of this list,

11

but identifies each of the applications in the event that Broad needs to respond to positions taken

12

by UC.

13

Broad respectfully requests that these motions be authorized as a single motion and that

14

Broad be given at least 25 pages for discussion of benefit of B1, which is common to all 12

15

patents, an additional 10 pages each for discussion of benefit of B2 and B6, which are common

16

to all 12 patents, and additional pages for discussion of benefit of each further application in the

17

priority chain of Broads Involved Patents.

18

III.

19
20
21
22

Motions For Judgment Based on Unpatentability of UCs Involved Claims

Motions for judgment pursuant to 37 C.F.R. 41.121(a)(1)(iii) and 208(a)(1) on the

grounds that all of UCs Involved Claims are unpatentable to UC:

47.

under 35 U.S.C. 112 for lack of adequate written description for all of UCs
Involved Claims because those claims all include limitations and subject matter

which were not possessed at the time of filing the Involved UC 859 application

by the four individuals currently named as inventors, e.g.:

a. an engineered system or method comprising b) a single molecule DNA-

targeting RNA comprising i) a targeter-RNA that hybridizes with the target

sequence, and ii) an activator-RNA that hybridizes with the targeter-RNA

wherein the activator-RNA and the targeter-RNA are covalently linked to one

another with intervening nucleotides, e.g. UC Involved Claim 165, see also

UC Involved Claims 166-200, 202-218, 220-222 and 224-247,

b. a method comprising a nucleotide sequence that is operably linked to a

10

control element operable for any desired cell type, e.g. UC Involved

11

Claims 171-172 and 189-190, or an engineered system or method

12

comprising a Cas9 protein wherein the Cas9 protein comprises one or

13

more Protein Transduction Domains) (PTD(s)) or wherein the one or

14

more PTD(s) aid in traversal of an organelle membrane, e.g. UC Involved

15

Claims 180 and 181, see also UC Involved Claims 182, 198-200, 206-208

16

and 216-218,

17

c. a method comprising creation of a double strand break in the target DNA

18

molecule which is repaired by a non-homologous end joining (NHEJ) repair

19

mechanism or creation of a double strand break in the target DNA molecule

20

which is repaired by a homology-directed repair mechanism which

21

incorporates a sequence of a donor polynucleotide into the target DNA

22

molecule, thereby editing the target DNA molecule, e.g. UC Involved Claims

23

178-179, or a method wherein the editing comprises modifying the target

DNA molecule by inserting a sequence of a donor polynucleotide, e.g. UC

Involved Claim 237; see also UC Involved Claims 196-197,

d. an engineered system or method wherein the CRISPR-Cas system comprises

two or more single molecule DNA-targeting RNAs, e.g. UC Involved Claim

195, see also UC Involved Claims 205 and 215,

e. an engineered system or method wherein one or both of the nucleic acids

of [a nucleic acid comprising a nucleotide sequence encoding a Cas9

protein] and [a nucleic acid comprising a nucleotide sequence encoding a

single molecule DNA-targeting RNA] are one or more vectors and

10

wherein the nucleotide sequence encoding said Cas9 protein and/or the

11

nucleotide sequence encoding said single molecule DNA-targeting RNA

12

are operably linked to a control element operable in a desired cell type,

13

e.g. UC Involved Claim 204, see also UC Involved Claims 167, 169, 170-

14

176, 186-194, 200, 209-210, 212 and 214, and

15

f. an engineered system comprising modification to secondary structure

16

wherein the modification comprises an engineered secondary structure, e.g.

17

UC Involved Claim 225 or wherein the modification comprises adding,

18

removing, or otherwise altering loops and/or hairpins in the single molecule

19

DNA-targeting RNA, e.g. UC Involved Claim 229 or wherein the one or

20

more modified nucleotides are selected from the group consisting of 2-

21

aminopurine, 5-bromo-uridine, pseudouridine, and 7-methylguanosine, e.g.

22

UC Involved Claim 235, see also UC Involved Claims 226-228, 230-234,

23

237-239 and 244;

48.

under 35 U.S.C. 112 for lack of enablement for all of UCs Involved Claims

because, in light of the state of the art, the disclosure does not contain sufficient

information to enable persons of ordinary skill in the art to make and use, without

undue experimentation, the full scope of the subject matter defined by claims that

include limitations to:

a. a system or method, for delivery to and use in any environment, including in a

desired cell type, including a cell having organellar DNA using a Cas 9

protein having one or more protein transduction domains (PTDs), that aid in

the traversal of the organelle membrane, wherein a target DNA molecule is

10

cleaved or edited or transcription of at least one gene encoded by the target

11

DNA molecule is modulated by a system comprising a single molecule DNA-

12

targeting RNA,

13

b. an engineered tracrRNA or single molecule DNA-targeting RNA transcribed

14

from a vector comprising a nucleotide sequence encoding the RNA that is

15

operably linked to a control element operable to transcribe from a plasmid,

16

phage or viral vector, including wherein the RNA is engineered to comprise

17

modification in secondary structure, artificial loop, hairpin and/or 5-end

18

extension or one or more modified nucleotides, for use and/or improved use in

19

a desired cell type,

20

c. a system or method of using a CRISPR system to create a double stranded

21

break that is repaired by gene editing, or to create a break that is repaired by

22

incorporation of a sequence of a donor polynucleotide, and

d. a system or method comprising two or more single molecule DNA-targeting

2
3

RNAs;
49.

under 35 U.S.C. 102(a) and/or 35 U.S.C. 102(e) based on prior art to UCs

Involved Claims, which is prior art to UCs Involved Claims, but does not render

Broads Involved Claims unpatentable, including each of:

a. Jinek, et al., A programmable dual-RNA-guided DNA endonuclease in

adaptive bacterial immunity. Science, 337, 816-821, (2012), and

Supplementary Papers, (published online June 28, 2012),

b. Cong, et al., Multiplex genome engineering using CRISPR/Cas systems.

10

Science, 339, 819-823, (2013), and Supplementary Papers (submitted Oct. 5,

11

2012, published online Jan. 3, 2013),

12

c. Mali, et al., RNA-guided human genome engineering via Cas9, Science, 339,

13

823-826 (2013), and Supplementary Papers (submitted Oct. 26, 2012,

14

published online Jan. 3, 2013),

15
16
17

d. U.S. Publication No. 2014/0342457 (Mali, et al.)(claiming priority to U.S.

Application No. 61/738,355) (Dec. 17, 2012),
e. Jinek, et al., pre-print publication of accepted manuscript, RNA programmed

18

genome editing in human cells, (published on Jan. 7, 2013 per

19

http://newscenter.berkeley.edu/2013/01/07/cheap-and-easy-technique-to-snip-

20

dna-could-revolutionize-gene-therapy),

21

f. Jiang, et al., RNA-guided editing of bacterial genomes using CRISPR-Cas9

22

systems, Nature Biotechnology, 31, 233-241 (2013), and Supplementary

23

Papers (submitted Nov. 20, 2012, published online Jan. 29, 2013), and

g. Jinek, et al., RNA programmed genome editing in human cells, eLife 2013;

2:e00471, 1-9 (2013), and Supplementary Papers (submitted to Elife on Dec.

15, 2012, published online Jan. 29, 2013);

50.

under 35 U.S.C. 103, for the subject matter of UCs Involved Claims, which is

prior art to UCs Involved Claims, but does not render Broads Involved Claims,

unpatentable, including each of the following in proper combination and/or with

one or more of the above 102 references, including:

a. Paddison et al., Short hairpin RNAs (shRNAs) induce sequence-specific

9
10

silencing in mammalian cells, Genes & Development 16, 948-58 (Jan. 31,
2002),

11

b. U.S. Publication 2006/0009402 (Zamore, et al.) (Jan. 12, 2006),

12

c. McIntyre and Fanning, Design and cloning strategies for constructing shRNA

13

expression vectors, BMC Biotechnology 6, 1-8 (2006), and Supplementary

14

Papers,

15

d. U.S. Publication 2010/0093617 (Barrangou, et al.) (April 15, 2010),

16

e. U.S. Publication 2011/0300538 (Barrangou, et al.) (Dec. 8, 2011),

17

f. U.S. Publication 2010/076057 (Sontheimer, et al.) (March 25, 2010),

18

g. Garneau, et al., The CRISPR/Cas bacterial immune system cleaves

19

bacteriophage and plasmid DNA, Nature, 468, 67-71 (Nov. 4, 2010),

20

h. Deltcheva, et al., CRISPR RNA maturation by trans-encoded small RNA and

21

host factor RNase III, Nature, 471(7340) (published online March 31, 2011),

i. Sapranauskas, et al., The Steptococcus thermophilus CRISPR/Cas system

provides immunity in Escherichia coli, Nucleic Acids Research, 39, 9275-

9282 (published online Aug. 3, 2011),

j. U.S. Publication 2015/0045546 (Siksnys, et al.)(as in U.S. Application

61/613,373) (March 20, 2012),

k. U.S. Publication 2015/0045546 (Siksnys, et al.)(as in U.S. Application

61/625,420) (April 17, 2012), and

l. Gasiunas, et al., PNAS Plus: Cas9-crRNA ribonucleoprotein complex

mediates specific DNA cleavage for adaptive immunity in bacteria,

10

Proceedings of the National Academy of Sciences, 109, E2579-E2586

11

(submitted May 21, 2012, published online Sept. 4, 2012).

12
13

IV.

Motions To Designate Claims As Not Corresponding To Count 1

Motions under 37 C.F.R. 41.121(a)(1)(i) and 41.208(a)(2) to designate as not

14

corresponding to Count 1 the following Broad Involved Claims on the grounds that these claims,

15

exemplary features of which are listed below, are neither anticipated by nor rendered obvious

16

over Count 1:

17

51.

selected protein, Staphylococcus aureus Cas9, patents and claims,

18

a. claims 1-30 of the 406 patent (all involved claims) and

19

b. claims 1-30 of the 308 patent (all involved claims);

20

52.

engineered vectors for delivery of engineered RNA and system components for

21

transcription and use in eukaryotic cells, patents and claims,

22

a. claims 1-43 of the 233 patent (all involved claims),

23

b. claims 1-14 of the 359 patent,

10

c. claims 1-25 of the 945 patent,

d. claims 1-25 of the 965 patent,

e. claims 1-23 of the 406 patent,

f. claims 1-25 of the 445 patent,

g. claims 1-23 of the 356 patent,

h. claims 1-24 of the 308 patent,

i. claims 1-24 of the 814 patent,

j. claims 1-20 of the 839 patent, and

k. claims 1-21 of the 641 patent;

10

53.

improved system, for improved localization to nucleus of eukaryotic cell, having

11

two or more nuclear localization signals, patents and claims,

12

a. claims 1-30 of the 445 patent (all involved claims),

13

b. claims 1-30 of the 814 patent (all involved claims), and

14

c. claim 7 of the 233 patent;

15

54.

improved system for use in nucleus of eukaryotic cell, having one or more nuclear

16

localization signals, patents and claims,

17

a. claims 1-30 of the 308 patent (all involved claims),

18

b. claims 1-28 of the 839 patent (all involved claims),

19

c. claims 3, 10 and 17 of the 359 patent,

20

d. claims 3, 13, 20 and 27 of the 945 patent,

21

e. claims 3, 12, 19 and 28 of the 965 patent,

22

f. claims 3, 15 and 26 of the 406 patent, and

23

g. claims 3, 14 and 24 of the 616 patent;

11

55.

improved tracr for delivery and use in eukaryotic cells, patents and claims,

a. claims 1-28 of the 839 patent (all involved claims),

b. claims 1-43 of the 233 patent (all involved claims),

c. claims 1-28 of the 641 patent (all involved claims), and

d. claims 6-8 of the 616 patent; and

56.

improved guide, for use in complex for use in eukaryotic cells, with further
secondary structures, claims 1-30 of the 616 patent (all involved claims).

Broad respectfully submits that these motions be authorized separately or as a single motion with

additional pages. 37 C.F.R. 41.201.

10
11
12

V.

Motions Under 37 C.F.R. 41.121(a)(3)

57.

A miscellaneous motion:
a. to allow Broad to have access to the prosecution histories of UCs pending,

13

unpublished (two of which did become publicly available today, March 3,

14

2016) applications related to the 859 application, namely, (i) U.S. Patent

15

Application No. 14/942,782; (ii) U.S. Patent Application No. 14/685,516; (iii)

16

U.S. Patent Application No. 14/685,514; (iv) U.S. Patent Application No.

17

14/685,513; (v) U.S. Patent Application No. 14/685,504; and (vi) U.S. Patent

18

Application No. 14/685,502, to evaluate whether any of these applications

19

should be added to this interference,

20
21
22
23

b. to require UC to keep the Board and Broad timely apprised of the issuance of
any notice of allowance for any claim in these applications, and
c. to require UC to advise each Examiner in these and any other UC related
applications of the existence of this Interference.

24
12

1
2

VI.

Motion For Judgment Based on Priority

58.

A motion under 37 C.F.R. 41.208(a)(4) seeking judgment based on priority.

3
4

Dated: March 3, 2016

Respectfully submitted,

5
6
7
8
9
10
11
12
13

/Steven R. Trybus/
Steven R. Trybus
Reg. No. 32,760
Counsel for Broad
Jenner & Block LLP
353 North Clark Street
Chicago, IL 60654
Telephone: (312) 222-9350
Facsimile: (312) 527-0484
strybus@jenner.com

13

CERTIFICATE OF FILING AND SERVICE

I hereby certify that on the 3rd day of March, 2016, a true and complete copy of the
foregoing BROAD LIST OF PROPOSED MOTIONS is being filed by 5:00 pm EST via
the Interference Web Portal. Pursuant to agreement of the parties, service copies are being
sent by e-mail by 8:00 pm EST to counsel for Senior Party as follows:
todd.walters@bipc.com
erin.dunston@bipc.com
travis.bliss@bipc.com
BFairchild@goodwinprocter.com
CStephens@goodwinprocter.com

/Steven R. Trybus/
Steven R. Trybus
Reg. No. 32,760
Counsel for Broad
Jenner & Block LLP
353 North Clark Street
Chicago, IL 60654
Telephone: (312) 222-9350
Facsimile: (312) 527-0484
strybus@jenner.com