WGS of Biobank iPSC lines

IMBA has generated an iPS CELL Biobank, which is anchored in the IMBA Stem Cell Core Facility (ISCCF). IMBA is willing to provide high-quality reference control panels of human induced pluripotent stem cell (iPSC) clones as a tool to the research community based on terms and conditions set forth in IMBA’s General Terms and Conditions for the Provision of iPS CELL Clones.

Material Transfer Agreement (genome edited iPSC clones) IMBA has generated an iPS CELL Biobank, which is anchored in the IMBA Stem Cell Core Facility (ISCCF). IMBA is willing to provide high-quality reference control panels of human induced pluripotent stem cell (iPSC) clones as a tool to the research community based on terms and conditions set forth in IMBA’s General Terms and Conditions for the Provision of iPS CELL Clones. 1) ORDER a. Order Date: b. Order Number: c. iPS CELL Lines and respective Clone(s): 2) RECIPIENT a. Institutional Contact: i. Name: ii. Address: iii. Legal Representative: iv. Title: v. Email: RECIPIENT is an ACADEMIC CUSTOMER : yes 0 no 0 If RECIPIENT is an ACADEMIC CUSTOMER1: b. Scientific Contact (RECIPIENT Scientist): i. Name: ii. Title: iii. Shipping Address: iv. Tel.: v. Email: c. Consignee: i. Name: ii. Tel.: iii. Email: 3) IMBA Institut fuer Molekulare Biotechnologie GmbH IMBA Stem Cell Core Facility (ISCCF) Dr. Bohr Gasse 3, 1030 Vienna, Austria Dr. Sofia Aligianni, Dr. Jennifer Volz Co-Heads, ISCCF Tel.: +43-1-79044-4880 Email: sofia.aligianni@imba.oeaw.ac.at jennifer.volz@imba.oeaw.ac.at RECIPIENT herewith represents and warrants that it agrees with the terms set forth in IMBA’s General Terms and Conditions for Provision of iPS CELL Clones. Date Signature on behalf of RECIPIENT by its duly authorized representative If RECIPIENT is an ACADEMIC CUSTOMER1: Read and acknowledged: Date Signature of RECIPIENT Scientist ANNEX A: Study Protocol IPSC Biobank ANNEX B: Cyto TuneTM Limited Use Label License ANNEX C: iPS Academia Japan User Notice ANNEX D: Sigma-Aldrich CRISPR Limited Label Use License Agreement ANNEX A: Study Protocol IPSC Biobank 1. TITLE (between 7-20 words) 2. LIST STUDY TEAM AND AFFILIATION Name Affiliation 3. CORRESPONDENCE Name Affiliation 4. EXPERIMENTAL PLAN a) Summary (between 150- 250 words) b) Rationale (between 300- 500 words) c) Objectives: Aims, Hypothesis (between 300- 500 words) d) Experimental Plan: Requested Cell Lines, Study Design, Methods, Statistical Part, Study Timeline, Ethical Considerations, Data Protection, Risks, up to 5 References (2000 words max) e) Applicant warrants that the experiments outlined above have been approved by its local ethics committee and all other relevant authorities:  YES  NO   IMBA’s General Terms and Conditions for Provision of (genome edited) iPS CELL Clones 1. Contract Terms These are the contract terms and conditions (“TERMS”) under which IMBA provides its (genome edited) iPS CELL Clones to RECIPIENT. These TERMS together with the MATERIAL TRANSFER AGREEMENT (including ANNEX A, B, C and D which are an integral part of the MATERIAL TRANSFER AGREEMENT) and the quotation create the contract (“CONTRACT”) between IMBA and RECIPIENT for the provision of (genome edited) iPS CELL Clones. The CONTRACT is only created when RECIPIENT accepts the TERMS, submits the signed MATERIAL TRANSFER AGREEMENT (including ANNEX A: Project Agreement and Ethical Approval) and the order has been accepted by IMBA. 2. Order, Delivery and Cancellation 2.1 Orders at ISCCF can only be placed through our web-based ordering system at https://www.imba.oeaw.ac.at/scientific-facilities/stem-cell-core-facility/webshop. The ISCCF order system automatically generates a MATERIAL TRANSFER AGREEMENT that needs to be signed off by RECIPIENT and uploaded to finalize the order. RECIPIENT will then receive an email by ISCCF that finally confirms your order. 2.2 Shipment of our (genome edited) iPS CELLS Clones usually takes up to 2 months from the ordering date. This delivery time is an approximate indication and is not guaranteed by IMBA. IMBA will try to meet the delivery dates specified in your order, depending on availability and any lead times that may apply. If speeding up or delaying the date of delivery would be helpful, please contact ipscellbiobank@imba.oeaw.ac.at to see if IMBA can reschedule your delivery. 2.3 The order can be cancelled free of charge within five (5) days of the order confirmation date. For cancellation of your order within this period please send an email to ipscellbiobank@imba.oeaw.ac.at . IMBA only accepts written cancellations. 2.4 A cancellation fee of 20 % of the total payment amount will be charged if the 5-day order period has passed. Once the (genome edited) iPS CELL Clones are ready for shipment no refund will be given. 3. Quality Control 3.1 IMBA wants RECIPIENT to receive the (genome edited) iPS CELL Clones in good condition. IMBA only sends out (genome edited) iPS CELL Clones that pass all internal quality control tests. 3.2 Even though IMBA´s (genome edited) iPS CELL Clones pass this stringent quality control, IMBA cannot offer a guarantee that they may work for your specific experiment or that they are appropriate for your specific requirements, as the (genome edited) iPS CELL Clones supplied to customers are handled in your laboratories and facilities outside IMBA´s supervision. 3.3 RECIPIENT can return (genome edited) iPS CELL Clones that are damaged or defective on delivery (except for loss and damage due to shipment), if RECIPIENT contacts us via email ipscellbiobank@imba.oeaw.ac.at within fourteen (14) working days from the day RECIPIENT receives the (genome edited) iPS CELL Clones. If RECIPIENT does not contact us within this 14-day period, the shipment will be deemed accepted. 4. Shipment 4.1 IMBA only provides (genome edited) iPS CELL Clones for shipment via your account through the commercial carriers FedEx or DHL. RECIPIENT will be responsible for transportation, the payment of transportation costs, applicable taxes and custom duties. 4.2 Orders are delivered and concluded when the commercial carrier takes over the (genome edited) iPS CELL Clones at the IMBA facility. At this point RECIPIENT becomes responsible for risk of loss and damage. 4.3 IMBA takes no responsibility for the condition of the (genome edited) iPS CELL Clones due to the shipment via FedEx or DHL. If any (genome edited) iPS CELL Clones are lost or damaged while it is being transported, IMBA will try to help RECIPIENT deal with the issue with the carrier. 4.4 IMBA does not clear (genome edited) iPS CELL Clones for import into your country. Doing so is RECIPIENT´s responsibility and IMBA requests a valid permit to avoid conflicts with RECIPIENT´s transportation carrier. If the order is ready to ship, but no valid permit is present, RECIPIENT will be informed via email. If IMBA does not receive all the necessary documents within two weeks, IMBA has the right to discard the order and only pending items will be refunded. 4.5 Should the shipment be refused or discarded by customs (or by import regulation agency) due to an invalid import permit, IMBA will not replace the order or shipping costs. 5. Pricing 5.1 All prices for (genome edited) iPS CELL Clones are published on the iPSC Biobank webshop website.These prices may be changed at any time without prior notice. 5.2 IMBA’s published prices do not include any taxes (including VAT), duties, levies or other government fees that may apply to your order. If they apply, it will be RECIPIENT’s responsibility to pay them. In any case, should a situation occur that requires IMBA to prepay them, IMBA will add them to RECIPIENT’s invoice. 6. Invoice and Payment 6.1 Invoices will be automatically generated after order confirmation and sent to RECIPIENT as a pdf document to RECIPIENT’s email address. 6.2 All payments shall be made in advance using VISA or Master Card. RECIPIENT may contact ISCCF for alternative routes of payment which will imply additional handling fees for manual invoicing. 6.3 If RECIPIENT`s payment is not approved by the credit card company, RECIPIENT´s order will be cancelled. If RECIPIENT´s payment is overdue, IMBA may charge RECIPIENT a late-payment charge, from the due date until paid, at the rate of one percent (1%) per month. 7. Product Use and User Restrictions 7.1 RECIPIENT agrees to use the iPS CELL Clones in full compliance with this agreement, the existing ethical approval (ANNEX A), all applicable laws, governmental regulations, guidelines, and ethical rules such as, for example, those relating to research involving the use of animals and recombinant DNA. Any new or additional use of the cells provided under this agreement that does not fall under the project description in ANNEX A is prohibited. , RECIPIENT is responsible for compliance with all regulations and guidelines applicable to the use, handling, disposal (including without limitation those governing disposal of hazardous materials) and storage of the iPS CELL Clones. RECIPIENT will obtain all permits, licenses or other approvals required by governmental authorities in connection with the receipt, handling, use, disposal and storage of iPS CELL Clones. RECIPIENT will take all necessary steps to ensure securest storage of iPS CELL Clones. RECIPIENT or RECIPIENT Scientist will inform IMBA without delay of any errors in data that they become aware of during the course of their study. 7.2 RECIPIENT agrees to use the (genome edited) iPS CELL Clones for internal research purposes only in RECIPIENT’s laboratories located in the country specified at page 1. Use of the (genome edited) iPS CELL Clones shall expressly exclude: (a) the use of cell-based potency, safety, or efficacy assays for any clinical manufacturing activity; (b) any bioproduction involving any form of clinical trials or production of biologics-based therapeutic drugs including protein-based therapeutics; (c) any in vivo and ex vivo human clinical use, including without limitation, any administration into humans or any diagnostic or prognostic use; (d) any in vivo veterinary or livestock use, or non-research agricultural use; (e) the manufacture, distribution, importation, exportation, transportation, sale, offer for sale, marketing, promotion or other exploitation or use of, or as, a testing service, batch/lot/product release assays in each case for manufacturing therapeutics or therapeutic candidates, or therapeutic or diagnostic for humans or animals; (f) creation of any animal models or use of derivatives therefrom; (g) use in human germ line editing; (h) use in gene drive applications; (i) use in production of illicit drugs; or (j) use in tobacco. 7.3 RECIPIENT acknowledges that the genome edited iPS CELL Clones were made using certain patent rights (CRISPR-BASED GENOME MODIFICATION AND REGULATION) obtained by IMBA under a Limited Use Label License from Sigma-Aldrich Co.LLC, the terms of which are set out at ANNEX D. RECIPIENT agrees to accept and follow the user restrictions as specified in ANNEX D (“Sigma-Aldrich CRISPR Limited Label Use License Agreement”). 7.4 The (genome edited) iPS CELL Clones will not be used (i) for any administration or application to humans, or (ii) for humans or animals for therapeutic, diagnostic or prophylactic purposes, the use including, but not limited to, clinical applications, cell therapy, transplantation and regenerative medicine. 7.5 IMBA retains ownership of the iPS CELL Clones, including all iPS CELL Clones genetically modified by IMBA which retain the ability to self-replicate, and including all intellectual property rights therein. No exclusive rights to the (genome edited) iPS CELL CLONES or their data are offered and/or granted under this agreement. 7.6 RECIPIENT acknowledges that the iPS CELL Clones were made using a CytoTuneTM iPS Reprogramming Kit obtained by IMBA under a Limited Use Label License from Life Technologies Corporation, the terms of which are set out at ANNEX B and which prohibit use of the iPS CELL Clones for commercial applications. RECIPIENT agrees that it will not use or permit the use of the iPS CELL Clones for any such commercial application and will comply with the terms set out at ANNEX B as they apply to the iPS CELL Clones supplied under this AGREEMENT. Without prejudice to the generality of the foregoing, RECIPIENT understands that some uses of the iPS CELL Clones may require a license from Life Technologies Corporation or its licensor, DNAVEC Corporation. IMBA accepts no liability in relation thereto. Any queries relating to the scope of ANNEX B and any requirement for a separate license should be directed to Life Technologies and/or DNAVEC. Further, generating induced Pluripotent Stem Cells (iPSC) requires using the “Yamanaka factors” to induce reprograming into iPSC. These were discovered by Prof Shinya Yamanaka's team at Kyoto University. These factors and related methods are the subject of patents or patent applications held by Kyoto University. These rights cannot be commercialized without a license obtained from iPS Academia Japan, Inc. (http://www.ips-cell.net/e/index.php). 7.7 FOR-PROFIT USERS must accept and follow the user restrictions as specified in ANNEX C (“User Notice”). 7.8 RECIPIENT shall indemnify and hold IMBA harmless against any breach of these provisions by RECIPIENT, whether or not such breach was culpably committed (including the full costs of representation by an attorney of IMBA’s choice, all fees incurred, etc.). 8. Personal Data, Data Protection and Data Processing 8.1 The (genome edited) iPS CELL Clones will be provided by IMBA to the RECIPIENT without any identity information (personal data as defined in Art 4 Subsection 1 GDPR) of the individuals / donors. IMBA represents and warrants that it has complied with all legal requirements and obtained all patient consents necessary for the use of the (genome edited) iPS CELL Clones. 8.2 RECIPIENT must adhere to the applicable national data protection regulations and the EU General Data Protection Regulation (GDPR) when handling (genome edited) iPS CELL Clones and data related to and arising from the usage of (genome edited) iPS CELL Clones. 8.3 RECIPIENT will not make any attempt, neither alone or in conjunction with any other information, to identify the original donors of the (genome edited) iPS CELL Clones or data. RECIPIENT agrees not to use the requested datasets, either alone or in concert with any other information, to identify or contact individual participants from whom data and/or samples were collected. RECIPIENT also agrees not to generate information (e.g., facial images or comparable representations) that could allow the identities of research participants to be readily ascertained. 8.4 (Genome edited) iPS CELL Clones and/or data generated from (genome edited) iPS CELL Clones may be subject to informed consent from donors and donors may withdraw their consent. If such consent is withdrawn, RECIPIENT agrees to immediately destroy any (genome edited) iPS CELL Clones upon IMBA's requests due to withdrawal of informed consent or other regulatory issues. RECIPIENT shall provide IMBA with a confirmation of disposal stating that the iPS CELL Clones were destroyed without any undue delay, but at the latest ten (10) calendar days after IMBA’s request. 8.5 If genetic data and/or biomaterial derived from (genome edited) iPS CELL Clones are being distributed to third parties, a service agreement or MDTA (if research collaboration) at least as stringent as this agreement needs to be in place which ensures adherence to applicable national data protection regulations and the EU General Data Protection Regulation (GDPR)by the third party. 9. Publications The RECIPIENT shall have the right to publish its findings and results from the research with the iPS CELL Clones, provided that IMBA and ISCCF are acknowledged as the source of the iPS CELL Clones. Findings and results may only be published in such a form that does not permit any conclusions to be drawn about the respective donors. 10. Limitations of Liability 10.1 Any (genome edited) iPS CELL Clones delivered pursuant to this CONTRACT are understood to be experimental in nature and may have hazardous properties such as containing viruses, latent viral genomes, and other infectious agents. RECIPIENT expressly agrees to treat (genome edited) iPS CELL Clones as if they are not free of contamination and to ensure that they are handled by trained personnel under laboratory conditions that afford adequate biohazard containment. RECIPIENT assumes full responsibility for safe handling of (genome edited) iPS CELL Clones. 10.2 IMBA DOES NOT GUARANTEE OR MAKE ANY REPRESENTATION OR WARRANTY WHATSOEVER, WHETHER EXPRESSED OR IMPLIED, INCLUDING WITHOUT LIMITATION WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE (GENOME EDITED) IPS CELL CLONES WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY RIGHTS. ANY APPLICABLE STATUTORY GUARANTEES OR WARRANTIES ARE HEREBY EXPRESSLY EXCLUDED. 10.3 Any use of the (genome edited) iPS CELL Clones by RECIPIENT shall be at the sole risk and responsibility of RECIPIENT. RECIPIENT hereby agrees to indemnify IMBA against any demands, claims, suits, or actions against IMBA arising out of or in connection with RECIPIENT’s use of (genome edited) iPS CELL Clones, except for those caused by IMBA’s willful misconduct or gross negligence. Any liability of IMBA for negligence of any kind, loss of profit, and indirect damages shall be excluded in any case. 10.4 Our maximum aggregate liability arising out of or in connection with the CONTRACT is limited to the amount paid to us for the (genome edited) iPS CELL Clones. However, these provisions do not limit our liability for death or personal injury caused by gross negligence, fraud, misrepresentation, or any other liability that cannot be excluded by law. 10.5 Delivery dates and times are estimates only and IMBA will not be liable (in CONTRACT, delict, tort or otherwise) for any losses, expenses, claims or damages caused by a late delivery. 11. RECIPIENT`s Warranties: 11.1 RECIPIENT is responsible for compliance with all relevant statutes, legislation, regulations, and guidelines applicable to the use, handling, disposal (including without limitation those governing disposal of hazardous materials) and storage of the (genome edited) iPS CELL Clones and Personal Data including adherence to all relevant requirements of the GDPR. RECIPIENT will obtain all permits, licenses or other approvals required by governmental authorities in connection with the receipt, handling, use, disposal and storage of the (genome edited) iPS CELL Clones and Personal Data. RECIPIENT will take all necessary steps to ensure securest storage of the (genome edited) iPS CELL Clones and Personal Data. RECIPIENT warrants that the experiments outlined in ANNEX A have been approved by its local ethics committee and all other relevant authorities. RECIPIENT warrants to comply with all requirements of the ethic approval, including any requirements in the original patient consent, even if the ethic approval restricts the project description listed in ANNEX A. 11.3 RECIPIENT warrants not to make any attempt, neither alone or in conjunction with any other information, to identify the original donors of the (genome edited) iPS CELL Clones and Personal Data. 11.4 In case donors of (genome edited) iPS CELL Clones and Personal Data withdraw consent of use, IMBA will notify RECIPIENT of such (genome edited) iPS CELL Clones and/or Personal Data and RECIPIENT warrants to destroy respective (genome edited) iPS CELL Clones and Personal Data immediately and verifiably. 12 Entire Contract 12.1 The CONTRACT represents the entire agreement between RECIPIENT and IMBA regarding the (genome edited) iPS CELL Clones IMBA provides to RECIPIENT under it and supersedes and replaces any previous agreements between the parties (whether written or oral). Any additional and/or different terms and conditions that RECIPIENT may provide to IMBA, are material alternations and IMBA rejects them. IMBA’s offer to provide (genome edited) iPS CELL Clones is expressly limited to the TERMS of the CONTRACT. The CONTRACT cannot be amended or modified unless IMBA agrees in writing. 12.2 IMBA reserves the right to change these TERMS at any time. Any changes made to these TERMS will not apply to the CONTRACT between the parties for any order IMBA receives before the changes are made. 13 Miscellaneous 13.1 IMBA will not be responsible or liable for failing to perform its obligations under the CONTRACT to the extent caused by circumstances beyond our reasonable control. 13.2 IMBA’s failure to exercise any rights under the CONTRACT is not a waiver of IMBA’s rights to damages for RECIPIENT´s breach of CONTRACT and is not a waiver of any subsequent breach. If any provision or part of the CONTRACT is found by any court of competent jurisdiction to be invalid or unenforceable, such invalidity or unenforceability will not affect the other provisions of the CONTRACT. No person other than RECIPIENT or IMBA will have any rights under the CONTRACT. Headings are for convenience only and shall not be used in the interpretation of these TERMS. 13.3 RECIPIENT agrees to keep confidential any non-public technical information, commercial information (including prices, without limitation) or instructions (including any gene sequences, oligo types or sequences) received from IMBA as a result of discussions, negotiations and other communications between the parties in relation to products or services from the ISCCF. 13.4 This CONTRACT does not limit IMBA’s right to distribute (genome edited) iPS CELL Clones to others, use (genome edited) iPS CELL Clones for its own purpose or publish documents relating to (genome edited) iPS CELL Clones. 13.5 This CONTRACT and any disputes or claims arising out of or in connection with it are governed by the laws of Austria, excluding its rules of conflict, and excluding the UN Convention on the International Sale of Goods. The Vienna Commercial Court (Handelsgericht Wien) shall have exclusive jurisdiction for all disputes arising out of or in connection with this agreement. ANNEX B: Cyto Tune™ Limited Use Label License: Notice to Purchaser: This product is authorized for reprogramming methods that involve or pertain to the preparation of iPS cells or related cells. The purchase of this product conveys to the purchaser the limited, non-transferable right to use the purchased amount of product for internal use and for educational purposes. No right to resell this product or any of its components, or iPS cells or related cells generated by use of the product, or derivatives thereof (hereafter “the Materials”) is conveyed expressly, by implication, or by estoppels. For clarity, purchasers have the right to use third party service providers for generating iPS cells and derivatives for the benefit of such purchasers. Purchasers can deposit the Materials with not-for-profit repositories (“Repositories”) and transfer cells to non-for-profit research entities (not affiliated with a for-profit organization) for their internal research. Such recipient Repositories and not-for-profit research entities are allowed to distribute the Materials not-for financial gain to other users for their internal research. If the Materials are transferred to other users in accordance with the terms of this label license accompanying the product (hereafter “Label License”), the transferring party should notify recipients of such Materials of these terms by transferring a copy of the Label License to the recipients. To obtain commercial rights for the sale of the Materials or for a fee-for-service generation the Materials other than as allowed in paragraph 1 above, purchasers are requested to contact DNAVEC Corporation at cytotune@dnavec-corp.com. For all other commercial applications relating to the use of the Materials, purchasers might be required to contact iPS Academia Japan. Customers may contact iPS Academia Japan either directly at license@ips-ac.co.jp or through DNAVEC Corporation.   ANNEX C: iPS Academia Japan User Notice Definitions: 1. IMBA: Institut fuer Molekulare Biotechnologie GmbH. 2. iPS-AJ: iPS Academia Japan, Inc. 3. Product: iPS cells which IMBA provides and are claimed in the patents and patent applications mentioned below. 4. User: Person or entity who purchased Product from IMBA. 5. Pluripotent Cells: iPS cells provided by IMBA. 6. Progeny: Cells derived by User from the Pluripotent Cells which retain the ability to self-replicate, retain ability to differentiate into cell types from all three germ layers and remain in an undifferentiated state whether or not said cells are genetically modified and further including cell lines cloned from such cells so long as the cells retain the ability to self-replicate, retain ability to differentiate into cell types from all three germ layers and remain in an undifferentiated state. 7. Modification: Cells which are created by User through the use of the Pluripotent Cells or Progeny, but which (i) do not differentiate into cell types from all three germ layers and (ii) are in a partially or terminally differentiated state. 8. Materials: Pluripotent Cells, Progeny and Modification. 9. Commercial Use: Any activity by a User including at least one of the following activities: (i) use of the Pluripotent Cells or Progeny, for manufacture of related products distributed and/or sold to a third party including but not limited to culture media and equipment; (ii) use of the Pluripotent Cells, Progeny or Modifications to provide a service, information or data to a third party for financial gain; (iii) use of the Pluripotent Cells, Progeny or Modifications for screening small molecular compounds, large molecular compounds, antibodies, proteins, peptides and so on as potential pharmaceutical compounds. For the avoidance of misunderstanding, target discovery, target validation or assay development are excluded. Moreover, use of the Pluripotent Cells, Progeny or Modifications for screening by not-for-profit organizations solely for academic, educational and not-for-profit purposes is not considered as Commercial Use, but industry sponsored screening conducted by not-for-profit organizations is considered as Commercial Use; (iv) sale, lease, distribution or transfer of Pluripotent Cells, Progeny or Modifications to third parties for financial gain; or (v) sale, lease, distribution or transfer of Pluripotent Cells or Progeny to for-profit organizations not for financial gain. Note: “financial gain” here means any financial benefit or gain earned by User which consideration or revenue of a transaction exceeds its cost of operating the transaction.   User Restrictions: 1. The Product and its use are subject to one or more of EP Patent Nos. 1970446, 2462225, 2853592 and other corresponding patents and patent applications which iPS-AJ have been granted license rights with a sub-licensable right. 2. The purchase of the Product conveys to User a limited, non-exclusive and non-transferable right (without the right to sell, repackage, or further sub-license) under the patents set out in Section 1 above to use the purchased amount of the Product and the derivatives of the Product for User’s internal research (whether User is a not-for-profit or for-profit organization). No other right is granted to User whether expressly, by implication, by estoppel or otherwise. In particular, the purchase of the Product does not include nor carry any right or license to use, develop or otherwise exploit the Product commercially, and no rights are conveyed to User to use the Product for any other purpose. 3. User may use Materials for its internal research in its laboratories located in the country and area specified, but Commercial Use of Materials by User shall be restricted and be required with appropriate license from iPS-AJ. For clarity, in the case that User is a not-for-profit organization, including academia, governmental body and other not-for-profit organization, internal research use of Materials by User for academic, educational or other non-commercial purposes, or transfer of Materials to not-for-profit organizations for non-commercial purposes is not restricted. 4. User agrees to use Materials in compliance with all applicable statutes and regulations, but not to use Materials for any administration or application to humans. Moreover, User agrees not to use Materials for humans or animals for therapeutic, diagnostic or prophylactic purposes, the use including, but not limited to, clinical applications, cell therapy, transplantation and regenerative medicine without an appropriate license. 5. For information on taking a license to the patent rights for purposes other than those permitted above, please directly contact with License Division, iPS-AJ. Contact Details: iPS Academia Japan, Inc. 207 International Science Innovation Building East Wing, Kyoto University 36-1 Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan E-mail: license@ips-ac.co.jp Fax: +81-75-761-3577 ANNEX D: Sigma-Aldrich CRISPR Limited Label Use License Agreement This delivered biological material and/or data (“Service”or Product) and its use are the subject to the patent applications and issued patents that entered their respective National Stage from PCT International Pub. No. WO 2014/089290, controlled by Sigma-Aldrich Co., LLC (“SIGMA”). BEFORE USING THIS SERVICE or PRODUCT, PLEASE READ THE TERMS AND CONDITIONS SET FORTH IN THIS LICENSE AGREEMENT. YOUR USE OF THIS SERVICE SHALL CONSTITUTE ACKNOWLEDGMENT AND ACCEPTANCE OF THESE TERMS AND CONDITIONS. The purchase of this Service or Product conveys to you (the “Buyer”) the non-transferable (except as otherwise set forth in this label License Agreement) right to use the purchased Service or Product for Licensed Research Use (as defined below) subject to the conditions set out in this License Agreement. If you wish to use this Service or Product for any purpose other than Licensed Research Use, you must first obtain an appropriate license (see information set out below). This Service or Product may not be used for any purpose other than Licensed Research Use. Your right to use this Service or Product for Licensed Research Use is subject to the following conditions and restrictions: 1. “Licensed Research Use” means any use for research purposes, with the following exceptions: (i) Buyer may not sell or otherwise transfer the Service or Product (including without limitation any material that contains the Service or Product in whole or part or any Related Material to any other third party (except that you may transfer the Service or Product, including without limitation any material that contains the Service or Product in whole or in part, or any Related Material to a bona fide collaborator or to a service or Product provider, to perform services solely on your behalf), or use the Service or Product or any Related Material to perform services for the benefit of any other person or entity; (ii) Buyer may use only the purchased amount of the Service or Product and components of the Service or Product, and shall use any Related Material, only for their internal research within the Field, and not for any Commercial Purposes; (iii) Buyer shall use the Service or Product and any Related Material in compliance with all applicable laws and regulations, including without limitation applicable human health and animal welfare laws and regulations; (iv) SIGMA shall provide no warranties of any kind to the Buyer (statutory or implied) concerning the Patent Rights, the Service or product or any Related Materials, 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) SIGMA shall expressly disclaim any warranty regarding results obtained through the use of the Service or Product or any Related Materials, including without limitation any claim of inaccurate, invalid or incomplete results; (vi) SIGMA, and their directors, officers, employees and agents, shall have no liability to the Buyer, 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 Buyer shall indemnify, defend, and hold harmless SIGMA and their current and former directors, officers, employees and agents, and their respective successors, heirs and assigns (the “Indemnities”) against any liability, damage, loss, or expense (including without limitation reasonable attorneys’ fees and expenses) incurred by or imposed upon any of the Indemnitees 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 Buyer hereunder or any breach of this License Agreement by such Buyer; and (viii) the Service or Product and its use may be the subject of one or more issued patents and/or pending patent applications owned by SIGMA and the purchase of the Service or Product does not convey a license under any claims in the foregoing patents or patent applications directed to the production or commercialization of the Service. 2. For purposes of Section 1 above, the following definitions shall apply: “Commercial Purposes” means (a) the practice, performance or provision of any method, process or service, or (b) the manufacture, sale, use, distribution, disposition or importing of any product, in each case (a) or (b) for consideration, e.g., a fee, 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) the use of cell-based potency, safety, or efficacy assays for any clinical manufacturing activity; (b) any bioproduction involving any form of clinical trials or production of biologics-based therapeutic drugs including protein-based therapeutics; (c) any in vivo and ex vivo human clinical use, including without limitation, any administration into humans or any diagnostic or prognostic use; (d) any in vivo veterinary or livestock use, or non-research agricultural use; (e) the manufacture, distribution, importation, exportation, transportation, sale, offer for sale, marketing, promotion or other exploitation or use of, or as, a testing service, batch/lot/product release assays for manufacturing therapeutics or therapeutic candidates, or therapeutic or diagnostic for humans or animals; or (f) creation of any animal models or use of derivatives therefrom. 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