Caribou Limited Use Label License

This purchase of a transgenic mouse model (“Model”) is subject to the following terms and conditions. The Model is sold to the purchaser (“Purchaser”) subject to a license agreement (“MRC License”) for the use of certain Class 2 Type II CRISPR-Cas9 intellectual property by and between Medical Research Council, as part ofUnited Kingdom Research and Innovation (“MRC”), and Caribou Biosciences, Inc. (“Caribou”).

The use of the Model is subject to this “Limited Use Label License: Research Use Only” license, which conveys to the Purchaser the limited, non-transferable right to use the Model only as expressly permitted by this Limited Use Label License.

The purchase of the Model conveys to the Purchaser a limited, non-transferable right to use the Model, solely as provided to the Purchaser, together with (i) progeny or derivatives of the Model generated by the Purchaser (including but not limited to cells), and (ii) cells, tissue, and other biological material extracted or derived from the Model or its corresponding progeny or derivatives (collectively, the Model, as provided, and (i) and (ii) are referred to as “Material”) only to perform internal research for the sole benefit of the Purchaser.

The Purchaser cannot sell or otherwise transfer Material to a third party or otherwise use the Material for any Excluded Use. Notwithstanding the foregoing, the Purchaser may transfer Material to a third party under a contractual obligation to perform research for the sole benefit of the Purchaser or to a third party that is a non-profit performing collaborative research with the Purchaser; provided, however, that any such Material is accompanied by this Limited Use Label License.

It is the Purchaser’s responsibility to use the Material in accordance with all applicable laws and regulations.

For information on obtaining additional rights, including commercial rights, please contact licensing@cariboubio.com or Caribou Biosciences, Inc., 2929 7th Street, Suite 105, Berkeley, CA 94710 USA, Attn: Licensing.

The Purchaser shall Indemnify the Caribou Indemnitees from and against any and all Losses resulting from Third-Party Claims arising out of or relating to a breach by the Purchaser of any provision of the Limited Use Label License or arising from the Purchaser’s use, care or permitted transfer of the Model and/or any Material.  Purchaser’s obligation to Indemnify the Caribou Indemnitees shall not apply to the extent that any such Losses arise from the negligence or intentional misconduct of any Caribou Indemnitee.

The Purchaser shall Indemnify Caribou’s Licensors’ Indemnitees against any and all losses, damages, costs, fees, and expenses resulting from any claims or suits brought by any Third Party arising out of any rights granted to the Purchaser in respect of the PCT/US2013/032589 patent family under the Limited Use Label License; except to the extent such losses, damages, costs, fees, and expenses result from the gross negligence or willful misconduct of a Caribou’s Licensors’ Indemnitee.

The Purchaser shall Indemnify (by counsel acceptable to HHMI) the HHMI Indemnitee from and against any liability, cost, expense, damage, deficiency, loss, or obligation of any kind or nature (including, without limitation, reasonable attorneys’ fees and other costs and expenses of defense) based upon, arising out of, or otherwise relating to any Third-Party claim based upon, arising out of, or otherwise relating to any rights granted to the Purchaser in respect of the PCT/US2013/032589 patent family under the Limited Use Label License. The previous sentence will not apply to any such claim that is determined with finality by a court of competent jurisdiction to result solely from the gross negligence or willful misconduct of a HHMI Indemnitee.

Caribou, Caribou’s Licensors and HHMI are not a party to this Limited Use Label Licence and has no liability to the Purchaser or any user of the Model or Material, but each of Caribou, Caribou’s Licensors and HHMI is an intended third-party beneficiary of this Limited Use Label License and certain of its provisions are for the benefit of Caribou, Caribou’s Licensors and/or HHMI and are enforceable by each such party in its own name.

Nothing in this Limited Use Label License shall be construed to confer any rights upon the Purchaser by implication, estoppel, or otherwise as to any technology or patent rights of Caribou or any other entity other than as expressly set out in this Limited Use Label Licence.

For the purposes of this Limited Use Label License the following definitions shall apply:

Caribou Indemnitees” means Caribou and its directors, officers, and employees.

Caribou’s Licensors” meansThe Regents of the University of California and the University of Vienna.

Caribou’s Licensors’ Indemnitees” means Caribou’s Licensors, the sponsors of the research that led to the PCT/US2013/032589 patent family, the inventors of the PCT/US2013/032589 patent family who assigned their rights to Caribou’s Licensors/HHMI, and their employers, and the officers, employees, and agents of any of the foregoing.

Excluded Use” means any and all: (a) commercial activity including, but not limited to, any use in manufacturing and/or product or quality control; (b) preclinical or clinical testing or other activity directed toward the submission of data to the U.S. Food and Drug Administration, or any other regulatory agency in any country or jurisdiction where the active agent in such studies comprises the Material; (c) use to provide a service, information, or data for a third party; (d) use for human or animal therapeutic, diagnostic, or prophylactic purposes or as a product for therapeutics, diagnostics, or prophylaxis; (e) activity in an agricultural field trial or any activity directed toward the submission of data to the U.S. Department of Agriculture or any other agriculture regulatory agency; (f) high throughput screening drug discovery purposes (i.e., the screening of more than 10,000 experiments per day) as well as scale-up production activities for commercialization; (g) cell line or animal development for purposes of bioproduction of recombinant proteins; (h) modification of the human germline, including editing human embryo genomes or reproductive cells; and/or (i) stimulation of biased inheritance of a particular gene or trait or set of genes or traits (“gene drive”).

Indemnify” means to defend, hold harmless and indemnify.

Intellectual Property” means the patents relating to Class 2 Type II CRISPR-Cas9 compositions and methods licensed to MRC by Caribou under the MRC Licence. Details of the Intellectual Property can be found in Appendix A. For clarity, unless otherwise shown in Appendix A, Intellectual Property includes the PCT/US2013/032589 patent family.

Losses” means any and all losses, damages, costs, fees, liability, or expense (including reasonable legal expenses and attorneys’ fees).

HHMI” means the Howard Hughes Medical Institute, a non-profit medical research organisation with headquarters in Chevy Chase, MD, USA.

HHMI Indemnitees” means HHMI and its trustees, officers, employees, and agents.

Third Party” means any person or entity other than Caribou or MRC or the Purchaser.

Third-Party Claims” means any and all suits, claims, actions, and demands, in each case brought by a Third Party.

Appendix A – Intellectual Property Licensed to the MRC by Caribou under the MRC License

Compositions and Methods of Nucleic Acid-Targeting Nucleic Acids

Owner: Caribou Biosciences, Inc.

CountryApplication number
Patent number
Filing date
Grant date
Status
US14/416,338
9,260,752
01/22/2015
02/16/2016 (exp. 03/12/2034)
Granted
US14/751,055
9,410,198
06/25/2015
08/09/2016 (exp. 03/12/2034)
Granted
US 14/751,05806/25/2015Pending
US14/977,514
9,909,122
12/21/2015
03/06/2018 (exp. 03/12/2034)
Granted
US15/159,619
9,725,714
05/19/2016
08/08/2017 (exp. 03/12/2034)
Granted
US15/159,776
10,125,361
05/19/2016
11/13/2018 (exp. 06/15/2034)
Granted
US15/202,518
9,803,194
07/05/2016
10/31/2017 (exp. 03/12/2034)
Granted
US15/344,48711/04/2016Pending
US15/660,906
9,809,814
07/26/2017
11/07/2017 (exp. 03/12/2034)
Granted
US15/904,28502/23/2018Pending
AU201423579403/12/2014Abandoned
AU2015101418
2015101418
03/12/2014
10/29/2015 (exp. 03/12/2022)
Granted
BR112015022061-403/12/2014Pending
CA2,905,43203/12/2014Pending
CN201480028062.103/12/2014Pending
EP14771135.203/12/2014Pending
GB1517172.103/12/2014Pending
HK(GB)16100993.903/12/2014Pending
IL24156303/12/2014Pending
IN5749/CHENP/201503/12/2014Pending
JP2016-50135703/12/2014Abandoned
JP2017-25068003/12/2014Pending
KR2015-7028606
10-1780885
03/12/2014
09/15/2017 (exp. 03/12/2034)
Granted
MXMX/a/2015/01305703/12/2014Pending
NZ712727
712727
03/12/2014
08/29/2017 (exp. 03/12/2034)
Granted
NZ72555403/12/2014Pending
RU2015140276
2662932
03/12/2014
07/31/2018 (exp. 03/12/2034)
Grantet
RU201812228803/12/2014Pending
SG 11201507378U 11201507378U03/12/2014
06/18/2018 (exp. 03/12/2034)
Granted
ZA 2015/07006
2015/07006
03/12/2014
02/22/2017 (exp. 03/12/2034)
Granted
WOPCT/US2014/02382803/12/2014National phase
US61/781,59803/14/2013Expired
US61/818,38205/01/2013Expired
US61/818,38605/01/2013Expired
US61/822,00205/10/2013Expired
US61/832,69006/07/2013Expired
US61/845,71407/12/2013Expired
US61/858,76707/26/2013Expired
US61/859,66107/29/2013Expired
US61/865,74308/14/2013Expired
US61/883,80409/27/2013Expired
US61/899,71211/04/2013Expired
US61/900,31111/05/2013Expired
US61/902,72311/11/2013Expired
US61/903,23211/12/2013Expired
US61/906,21111/19/2013Expired
US61/906,33511/19/2013Expired
US61/907,21611/21/2013Expired
US61/907,77711/22/2013Expired
US14/206,31903/12/2014Abandoned

RNA Modification to Engineer Cas9 Activity

Owner: Caribou Biosciences, Inc.

CountryApplication number
Patent number
Filing date
Grant date
Status
US15/390,58412/26/2016Pending
WOPCT/US2015/03754606/24/2015Expired
US62/017,11306/25/2014Expired
US62/065,51510/17/2014Expired
US62/088,27712/05/2014Expired
US14/791,19507/02/2015Abandoned

Methods for Increasing Cas9-Mediated Engineering Efficiency

Owner: Caribou Biosciences, Inc.

CountryApplication number
Patent number
Filing date
Grant date
Status
US14/836,753
9,970,030
08/26/2015
05/15/2018 (exp. 08/26/2035)
Granted
US15/887,89302/02/2018Pending
AU2015308910
2015308910
08/26/2015
03/22/2018 (exp. 08/26/2035)
Granted
CA2,959,07008/26/2015Pending
EP15763698.6
3 186 376
08/26/2015
03/20/2019 (exp. 08/26/2035)
Granted
HK(EP)17113988.808/26/2015Pending
IL25070008/26/2015Pending
NZ728437
728437
08/26/2015
05/24/2018 (exp. 08/26/2035)
Granted
SG11201701245008/26/2015Pending
ZA2017/00724
2017/00724
08/26/2015
04/25/2018 (exp. 08/26/2035)
Granted
WOPCT/US2015/047046 08/26/2015 National phase
US62/042,35808/27/2014Expired
US62/047,49509/08/2014Expired

Methods and Compositions for RNA-Directed Target DNA Modification and for RNA-Directed Modulation of Transcription

(Owned by The Regents of the University of California, the University of Vienna, and Emmanuelle Charpentier)

Exclusively licensed to Caribou Biosciences, Inc. by The Regents of the University of California and University of Vienna

CountryApplicationnumber
Patent number
Filing date
Grant date
Status
US13/842,85903/15/2013Allowed
US14/685,502
10,000,772
04/13/2015
06/19/2018 (exp. 03/15/2033)
Granted
US14/685,50404/13/2015Allowed
US14/942,782
10,227,661
11/16/2015
03/12/2019 (exp. 03/15/2033)
Granted
US15/138,604
10,113,167
04/26/2016
10/30/2018 (exp. 03/15/2033)
Granted
US15/435,23302/16/2017Pending
US15/803,42411/03/2017Pending
US15/915,02003/07/2018Pending
US15/925,54403/19/2018Pending
US15/947,68004/06/2018Pending
US15/947,70004/06/2018Pending
US15/947,71804/06/2018Pending
US15/959,71504/23/2018Pending
US15/959,73504/23/2018Pending
US15/959,76204/23/2018Pending
US15/959,78204/23/2018Pending
US15/959,80204/23/2018Pending
US15/965,59804/27/2018Pending
US15/965,60304/27/2018Pending
US15/981,80705/16/2018Pending
US15/981,80805/16/2018Pending
US15/981,80905/16/2018Pending
US16/033,00207/11/2018Pending
US16/033,00507/11/2018Pending
US16/033,01607/11/2018Pending
US16/136,15909/19/2018Pending
US16/136,16509/19/2018Pending
US16/136,16809/19/2018Pending
US16/136,17509/19/2018Pending
US16/201,83611/27/2018Pending
US16/201,84811/27/2018Pending
US16/201,85311/27/2018Pending
US16/201,85511/27/2018Pending
US16/201,86211/27/2018Pending
US16/201,86511/27/2018Pending
US16/276,34302/14/2019Pending
US16/276,34802/14/2019Pending
US16/276,35202/14/2019Pending
US16/276,35602/14/2019Pending
US16/276,36102/14/2019Pending
US16/276,36502/14/2019Pending
US16/276,36802/14/2019Pending
US16/276,37402/14/2019Pending
US16/277,09002/15/2019Pending
AEP1296/1403/15/2013Pending
AU2013266968
2013266968
03/15/2013
12/07/2017 (exp. 03/15/2033)
Granted
AU201722506003/15/2013Pending
BR1120140299441-003/15/2013Pending
CA2,872,24103/15/2013Pending
CL2014-0320803/15/2013Pending
CN201380038920.6
104854241
03/15/2013
07/14/2017 (exp. 03/15/2033)
Granted
CN201710585690.503/15/2013Pending
CO14-25953103/15/2013Pending
CR2014-053803/15/2013Pending
DE202013012240
202013012240
03/15/2013
02/02/2016 (exp. 03/31/2023)
Granted
DE202013012241
202013012241
03/15/2013
01/18/2016 (exp. 03/31/2023)
Granted
DE202013012242
202013012242
03/15/2013
02/02/2016 (exp. 03/31/2023)
Granted
DZ14078003/15/2013Pending
EA20140131903/15/2013Pending
EC2014-2870403/15/2013Pending
EG1887/201403/15/2013Pending
EP13793997.1
2800811
03/15/2013
05/10/2017 (exp. 03/15/2033)
Granted
EP17163434.8
3241902
03/15/2013
02/28/2018 (exp. 03/15/2033)
Granted
EP18152360.603/15/2013Allowed
GB1420270.9
GB2518764
03/15/2013
03/02/2016 (exp. 03/15/2033)
Granted
GB1601071.2
GB2537000
03/15/2013
03/08/2017 (exp. 03/15/2033)
Granted
GE201301367403/15/2013Pending
HK(GB)15106335.4
1207107
03/15/2013
08/25/2017 (exp. 03/15/2033)
Granted
HK(CN) 15112610.8
1211978
03/15/2013
05/04/2018 (exp.  03/15/2033)
Granted
HK(GB)17103002.1
1230233
03/15/2013
06/01/2018 (exp. 03/15/2033)
Granted
IDP0020140778303/15/2013Pending
IL23546103/15/2013Allowed
IL26156303/15/2013Pending
IL26156503/15/2013Pending
IL26156603/15/2013Pending
IL26156703/15/2013Pending
IL26156803/15/2013Pending
IL26156903/15/2013Pending
IL26157003/15/2013Pending
IN2995/KOLNP/201403/15/2013Pending
JP2015-514015
6343605
03/15/2013
05/25/2018 (exp. 03/15/2033)
Granted
JP2018-09736903/15/2013Pending
KE2014/00217803/15/2013Pending
KR2014-703609603/15/2013Abandoned
KR2017-703406903/15/2013Pending
LY4958/201403/15/2013Pending
MA3766303/15/2013Pending
MXMX/a/2014/014477
349744
03/15/2013
08/10/2017 (exp. 03/15/2033)
Granted
MXMX/a/2017/01030903/15/2013Pending
MY201400310203/15/2013Pending
MY201870028503/15/2013Pending
NZ70132603/15/2013Pending
NZ714353
714353
03/15/2013
08/29/2017 (exp. 03/15/2033)
Granted
NZ72802403/15/2013Pending
NZ73066703/15/2013Pending
OM2014/0026803/15/2013Pending
PA90441-0103/15/2013Pending
PE002211-201403/15/2013Pending
PH1-2014-50257403/15/2013Pending
QA201411/0040003/15/2013Pending
SG1120 l 407702X
11201407702X
03/15/2013
03/20/2017 (exp. 03/15/2033)
Granted
SG10201701800Y
10201701800Y
03/15/2013
11/21/2018
Granted
SG10201809817U03/15/2013Pending
SY201412015603/15/2013Pending
TH140100706303/15/2013Pending
TN2014/0493
24223
03/15/2013
06/03/2016 (exp. 03/15/2033)
Granted
VAA201413835
118014
03/15/2013
11/12/2018
Granted
VAa20180854903/15/2013Pending
UZ2014055903/15/2013Pending
VN1-201400433503/15/2013Pending
XK2017/00002203/15/2013Pending
ZA2014/07881
2014/07881
03/15/2013
01/31/2018 (exp. 03/15/2033)
Granted
ZA2017/0072003/15/2013Pending
WOPCT/US2013/03258903/15/2013National phase
US61/652,08605/25/2012Expired
US61/716,25610/19/2012Expired
US61/757,64001/28/2013Expired
US61/765,57602/15/2013Expired
US14/403,47511/24/2014Abandoned
US14/685,51304/13/2015Abandoned
US14/685,51404/13/2015Abandoned
US14/685,51604/13/2015Abandoned
US15/090,51104/04/2016Abandoned

RNA-Directed DNA Cleavage by the Cas9-crRNA Complex

(Owned by Vilnius University and exclusively licensed to Pioneer Hi-Bred International, Inc.) Licensed to Caribou by Pioneer Hi-Bred International, Inc.  (now Corteva Agriscience)

CountryApplication number
Patent number
Filing date
Grant date
Status
US14/385,241
9,637,739
09/15/2014
05/02/2017 (exp.  03/15/2033)
Granted
US14/743,76406/18/2015Pending
US15/834,57812/07/2017Pending
US16/148,78310/01/2018Pending
BR112014023353-503/20/2013Pending
CA2,867,84903/20/2013Pending
CN201380023255.303/20/2013Pending
EA201491728
029544
03/20/2013
04/30/2018 (exp.  03/20/2033)
Granted
EP13715080.103/20/2013Pending
HK(EP) 15107124.703/20/2013Pending
IN7846/DELNP/201403/20/2013Pending
JP2015-501880
6423338
03/20/2013
11/14/2018 (exp. 03/20/2033)
Granted
JP2018-19657403/20/2013Pending
MXMX/a/2014/011279 03/20/2013Pending
ZA2014/06897
2014/06897
03/20/2013
12/23/2015 (exp.  03/20/2033)
Granted
WOPCT/US2013/033106 03/20/2013National phase
WOPCTILT2013/00000603/15/2013National phase
US61/625,42004/17/2012Expired
US61/613,37303/20/2012Expired
US14/385,85709/17/2014Abandoned
US14/683,44304/10/2015Abandoned

Broad Limited Licence

This purchase of a transgenic mouse model (“Product”) is subject to the following terms and conditions. The Product is sold subject to a license agreement (“MRC Licence”) for the use of certain CRISPR-Cas9 intellectual property (“Intellectual Property”) by and between Medical Research Council, as part ofUnited Kingdom Research and Innovation (“MRC”), and The Broad Institute, Inc. (“Broad”).

The term “Limited License” means a license granted by MRC to a Third Party that is the final purchaser or transferee of the Product (a “Limited Licensee”) conveying to such Limited Licensee the non-transferable right to use Product(s) purchased from MRC, and any Products made by or on behalf of Limited Licensee that are progeny, modifications, improvements or derivatives of the Products purchased from MRC (“MRC Products”), solely for research (including research-related activities) conducted by such Limited Licensee or by a Third Party contract organization (“CRO”) solely on behalf of such Limited Licensee in accordance with all of the following requirements.  The Limited License shall be in written form and specify that (i) the Limited Licensee shall not use Products and MRC Products to perform services for the benefit of any other person or entity or sell or otherwise transfer Products or MRC Products (including without limitation any material that contains a Product or MRC Product in whole or in part) to any other person or entity except (1) as otherwise permitted under license to Limited Licensee from Broad or as otherwise permitted by Broad for non-profit use as provided at https://www.broadinstitute.org/partnerships/office-strategic-alliances-and-partnering/information-about-licensing-crispr-genome-edi or (2) to a CRO (whether directly or by instructing the MRC to transfer the Product to the Limited Licensee’s CRO) to the extent such CRO: (A) uses the Products or MRC Products solely for providing the service of: (aa) generating information or data on behalf of a Limited Licensee; or (bb) holding, re-deriving, or breeding of Products or MRC Products on behalf of a Limited Licensee (including returning the progeny thereof to the Limited Licensee), and (B) does not otherwise make use of the Patent Rights in providing such services to such Limited Licensee; (ii) the Limited Licensee shall use Products or MRC Products and components of the Products or MRC Products only for its internal research within the Field, which may include internal research within the Field in connection with product research, but not for the production, manufacture or exploitation of any product or Product or any Commercial Purposes; (iii) the Limited Licensee shall use Products or MRC Products in compliance with all applicable laws and regulations, including without limitation applicable human health and animal welfare laws and regulations; (iv) Institutions shall provide no warranties of any kind to the Limited Licensee (statutory or implied) concerning the Intellectual Property or Products or MRC Products, including without limitation, as to product quality, condition, description, merchantability, fitness for a particular purpose, noninfringement of intellectual property rights or the absence of latent or other defects, and all such warranties are hereby expressly disclaimed; (v) Institutions shall expressly disclaim any warranty regarding results obtained through the use of the Products or MRC Products, including without limitation any claim of inaccurate, invalid or incomplete results; (vi) Institutions and their directors, trustees, officers, employees, agents, faculty, affiliated investigators, and students, shall have no liability to the Limited Licensee, including, without limitation, for any loss of use or profits, business interruption or any consequential, incidental, special or other indirect damages of any kind, regardless of how caused and regardless of whether an action in contract, tort, strict product liability or otherwise; (vii) the Limited Licensee shall indemnify, defend and hold harmless the Indemnitees and HHMI Indemnitees against any liability, damage, loss, or expense (including without limitation reasonable attorneys’ fees and expenses) incurred by or imposed upon any of the Indemnitees or HHMI Indemnitees, as applicable, in connection with any claims, suits, investigations, actions, demands or judgments arising out of or related to the exercise of any rights granted to the Limited Licensee under the Limited License or any breach of the Limited License by such Limited Licensee, provided that, to the extent the foregoing is not permitted by law, the Limited Licensee agrees, to the extent permitted by law, that it, and not the Indemnitees or HHMI Indemnitees, as applicable, shall be responsible for any liability, damage, loss or expense arising out of or related to the exercise of any rights granted to the Limited Licensee under the Limited License or any breach of the Limited License by Limited Licensee; and (viii) the Product or MRC Products and its use may be the subject of one or more issued patents or pending patent applications owned by one or more Institutions and the purchase of the Product or MRC Products does not convey a license under any claims in the foregoing patents or patent applications directed to the Product or MRC Products or use, production or commercialization thereof, except as expressly set forth in the Limited License.  Nothing in this Limited License shall be construed to confer any rights upon Limited Licensee by implication, estoppel, or otherwise as to any technology or patent rights of Broad or any other entity other than the Intellectual Property.  In addition, nothing in this Limited License shall be construed to confer upon Limited Licensee or any Third Party any rights under or to the Intellectual Property outside of the Field. The Institutions and HHMI are not a party to this Limited Licence and has no liability to the Limited Licensee or any user of the Product or MRC Products (including without limitation any material that contains a Product or MRC Products in whole or in part), but each of the Institutions and HHMI is an intended third-party beneficiary of this Limited License and certain of its provisions are for the benefit of HHMI and/or the Institutions and are enforceable by each such party in its own name.

For the purposes of this Limited License, the following definitions shall apply:

Commercial Purposes” means (a) the practice, performance or provision of any method, process or service, or (b) the manufacture, production, sale, use, distribution, disposition or importing of any product, in each case (a) or (b) for consideration of any kind, for the purpose of sale or commercial exploitation, or on any other commercial basis.

Field” means use as a research tool for research purposes; provided, however, that notwithstanding the foregoing, the Field shall expressly exclude: (a) any human or clinical use, including, without limitation, any administration into humans or any diagnostic or prognostic use; (b) any human germline modification, including modifying the DNA of human embryos or human reproductive cells; (c) any in vivo veterinary or livestock use; (d) the development, manufacture, distribution, importation, exportation, transportation, sale, offer for sale, marketing, promotion or other exploitation or use of the Patent Rights or a Product for or as a testing service, therapeutic or diagnostic for humans or animals; (e) products that provide nutritional benefits and are regulated by a regulatory authority as a drug or biologic pursuant to Section 505 of the Federal Food, Drug, and Cosmetic Act of 1938, as amended, Section 351 of the Public Health Service Act of 1944, as amended, or any successor laws, or equivalent laws or regulations in jurisdictions outside the United States; (f) any agricultural use, including but not limited to the use or application in the cultivation, growth, manufacture, exportation, or production of any tobacco product; and (g) any use or application relating to gene drive.

HHMI” means the Howard Hughes Medical Institute, a non-profit medical research organisation with headquarters in Chevy Chase, MD, USA.

HHMI Indemnitees” means HHMI and its trustees, officers, employees, and agents.

Indemnitees” means each of the Institutions, their affiliates, and their current and former trustees, directors, officers, faculty, affiliated investigators, students, employees, and agents and their respective successors, heirs and assigns.

Institutions” means: (a) The Broad Institute, Inc., a non-profit Massachusetts corporation, with a principal office at 415 Main Street, Cambridge, MA 02142, USA; (b) Massachusetts Institute of Technology, a not-for-profit Massachusetts corporation with a principal place of business at 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA; (c) the President and Fellows of Harvard College, an educational and charitable corporation existing under the laws of the Commonwealth of Massachusetts, having a place of business at Smith Campus Center, Suite 727E, 1350 Massachusetts Avenue, Cambridge, Massachusetts 02138, USA; (d) University of Iowa Research Foundation, a not-for-profit corporation existing under the laws of the State of Iowa, having a place of business at 112 N. Capitol Street, 6 Gilmore Hall, Iowa City, IA 52242, USA; (e) the University of Tokyo, a national university corporation existing under the laws of Japan, having an office at 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; (f) The Rockefeller University, a not-for-profit New York corporation with a principal place of business at 1230 York Avenue, New York, NY 10065, USA; (g) New York University, a not-for-profit corporation existing under the laws of New York with a principal place of business at 70 Washington Square South, New York, NY 10012, USA; (h) New York Genome Center, a not-for-profit corporation existing under the laws of Delaware and with a principal place of business at 101 Avenue of the Americas, New York, New York 10013, USA; and (i) Whitehead Institute of Biomedical Research, a Delaware corporation with a principal place of business at 455 Main Street, Cambridge MA 02142, USA.

Intellectual Property” means the patents and materials relating to genome editing technology, including but not limited to CRISPR, developed by Dr. Feng Zhang and colleagues and licensed to MRC by Broad under the MRC Licence.  Details of the Intellectual Property can be found here www.har.mrc.ac.uk/crispr-limited-use-license/.

Appendix A – Intellectual Property licensed to MRC by Broad under the MRC License

BROAD TECHIDAPPLICANTSEXEMPLARY FAMILY SERIAL NOPATENT TITLE
BI-2011/008Broad, MIT, Harvard and RockefellerPCT/US2013/074611 CRISPR-CAS Component Systems, Methods and Compositions for Sequence Manipulation
BI-2011/008ABroad and MITPCT/US2013/074743CRISPR-CAS Systems and Methods for Altering Expressions of Gene Products
BI-2011/0088Broad, MIT and HarvardUS 14/259,420CRISPR-cAS Systems, Methods and Compositions For Sequence Manipulation In Eukaryotes
BI-2011/020Broad, MIT and Harvard PCT/US2013/051418Inducible DNA Binding Proteins and Genome Perturbation Tools and Applications Thereof
BI-2012/084ABroad and MITPCT/US2013/074825Methods, Systems and Apparatus for Identifying Target Seuqences for CAS Enzymes or CRISPR-CAS Systems for Target Sequences and Conveying Results Thereof
BI-2012/084BBroad, MIT and HarvardPCT/US2013/074812 Methods, Models, Systems and Apparatus for Identifying Target Sequences for CAS Enzymes or CRISPR-CAS Systems for Target Sequences and Conveying Results Thereof
BI-2013/003Broad, MIT and HarvardPCT/US2013/074667Delivery, Engineering and Optimization of Systems Methods and Compositions for Manipulation and Applications
BI-2013/003DBroad, MIT and HarvardPCT/US2014/041803Delivery, Engineering and Optimization of Systems Methods and Compositions for Manipulation and Applications
BI-2013/004EBroad, MIT and HarvardPCT/US2013/074691Engineering and Optimization of Improved Systems, Methods and Enzyme Compositions for Sequence Manipulation
BI-2013/004FBroad, MIT and HarvardPCT/US2013/074736Engineering and Optimization of Systems, Methods and Compositions for Sequence Manipulation with Functional Domains
BI-2013/004GBroad, MIT and HarvardPCT/US2013/074819Engineering of Systems, Methods and Optimized Guide Compositions for Sequence Manipulation
BI-2013/007Broad, MIT and HarvardUS 14/855,046Recombinant Virus And Preparations Thereof
BI-2013/066Broad, MIT and HarvardPCT/US2014/041B00 Delivery, Engineering and Optimization of Tandem Guide Systems, Methods and Compositions for Sequence Manipulation
BI-2013/073Broad and MITPCT/US2014/041806Functional Genomics Using CRISPR-Cas Systems, Compositions, Methods, Screens and Applications Thereof
BI-2013/085Broad, MIT and WhiteheadUS 15/141,348Functional Genomics Using CRISPR Cas Systems, Compositions, Methods, Screens and Applications Thereof
BI-2013/087JBroad, Editas*, Iowa and MITPCT/US2014/064663 CRISPR-Related Methods and Compositions with Governing gRNAS
BI-2013/087MBroad, Iowa and MITPCT/US2014/069902Compositions and Methods of Use of CRISPR-CAS Systems in Nucleotide Repeat Disorders
BI-2013/087VBroad, Iowa and MITPCT/US2014/069897 Compositions and Methods of Use of CRISPR-CAS Systems in Nucleotide Repeat Disorders
BI-2013/093Broad, MIT and TokyoUS 15/171,141CRISPR·CAS Systems, Crystal Structure and Uses Thereof
BI-2013/094Broad, MIT and RockefellerPCT/US2014/070135 Delivery, Use and Therapeutic Applications of the CRISPR-Cas Systems and Compositions for HBV and Viral Diseases and Disorders
BI-2013/098Broad and MITPCT/US2014/070068 CRISPR-CAS Systems and Methods for Altering Expression of Gene Products, Structural Information and Inducible Modular CAS Enzymes
BI-2013/099Broad, MIT and HarvardPCT/US2014/041804 DELIVERY AND USE OF THE CRISPR CAS SYSTEMS, VECTORS AND COMPOSITIONS FOR HEPATICITARGETING AND THERAPY
BI-2013/101Broad and MITPCT/US2014/070127 Delivery, Use and Therapeutic Applications of the CRISPR-Cas Systems and Compositions for Genomic Editing
BI-2013/103Broad and MITPCT/US2014/041808Delivery, Engineering and Optimization of Systems, Methods and Compositions for Targeting and Modeling Diseases and Disorders of Post Mitotic Cells
BI-2013/105Broad, MIT and HarvardPCT/US2014/041809Delivery, Use and therapeutic Applications of the CRISPR-Cas systems and Compositions for Targeting Disorders and Diseases Using Viral Components
BI-2013/107Broad and MITPCT/US2014/070057 Delivery, Use and Therapeutic Applications of the CRISPR-CAS Systems and Compositions for Targeting Disorders and Diseases Using NanoParticle Components
BI-2013/112Broad and MITPCT/US2013/074800 Functional Genomics Using CRISPR CAS Systems, Compositions, Methods, Knock Out Libraries and Applications Thereof
BI-2013/113Broad, MIT and HarvardPCT/US2014/070152Engineering Of Systems, Methods And Optimized Guide Compositions with New Architectures For Sequence Manipulation
BI-2014/005Broad, MIT, Harvard and TokyoPCT/US2014/070175 Systems, Methods and Compositions for Sequence Manipulation with Optimized Functional CRISPR-CAS Systems
BI-2014/061Broad, MIT and HarvardPCT/US2015/045504Genome Editing Using CAS9 Nickases
BI-2014/069Broad and MITUS 15/467,888Delivery, Use and Therapeutic Applications of the CRISPR-CAS Systems and Compositions for Modeling Competition of Multiple Cancer Mutations in Vivo
BI-2014/071Broad and MITUS 15/349,603Delivery, Engineering and Optimization of Systems, Methods and Compositions for Sequence Manipulation and Therapeutic Applications
BI-2014/072Broad and MITUS 15/467,949Use and Production of CHD8+/- Transgenic Animals with Behavioral Phenotypes Characteristic of Autism Spectrum Disorder
BI-2014/084Broad, MIT and HarvardUS 15/469,081Functional Screening with Optimized Functional CRISPR-Cas Systems
BI-2014/097Broad, MIT and HarvardPCT/US2015/067177 CRISPR Having or Associated with Destabilization Domains
BI-2014/100Broad, MIT and HarvardPCT/US2015/065385 Protected Guide RNAs (PGRNAs)
BI-2014/101Broad, MIT and HarvardUS 15/632,067RNA Targeting System
BI-2014/103Broad and MITPCT/US2015/067138 Unbiased Identification of Double-Stranded Breaks and Genomic Rearrangement by Genome-Wide Insert Capture Sequencing
BI-2014/106Broad and MITPCT/US2015/065393 Dead Guides for CRISPR Transcription Factors
BI-2014/107Broad and MITUS 15/619,735Escorted and functional Guides for CRISPR CAS Systems
BI-2014/108Broad and MITUS 5/619,737Delivery, Use and Therapeutic Applications of CRISPR Systems and Compositions for Genome Editing as to Hematopoletlc Stem Cells (HSCs)
BI-2014/113Broad and MITUS 15/640,103CRISPR MEDIATED IN VIVO MODELING AND GENETIC SCREENING OF TUMOR GROWTH AND METASTASIS
BI-2015/002Broad, MIT, Harvard and Tokyo PCT/US2016/038252 Engineering and Optimization of Systems, Methods, Enzymes and Guide Scaffolds of CAS9 Orthologs and Variants for Sequence Manipulation
BI-2015/052Broad and MITPCT/US2016/038034 CRISPR Enzyme Mutations Reducing Off-Target Effects
BI-2015/053MITPCT/US2016/038205 CRISPR Mediated Recording of Cellular Events
10086Broad and MITPCT/US2017/047458 Novel CRISPR Enzymes and Systems
10114Broad and MITPCT/US2017/053795Systematic Screening and Mapping of Regulatory Elements in Non-Coding Genomic Regions, Methods, Compositions, and Applications Thereof
10125Broad and MITUS 62/502,064
US 62/564,102
Methods for Identification and Modification of LNCRNA Associated with Target Genotypes and Phenotypes
10209Broad, Harvard, MIT, New York University and NY Genome Center62/529,573Methods for Designing Guides Sequences for Guided Nucleases

* Broad does not purport to grant any rights in the asterix’d applicant’s interest in these applications.