SOW_Q146170.PDF

Thank you for your interest in using JAX® Services. These Services are provided by The Jackson Laboratory to support biomedical discovery in the academic, biotechnology and pharmaceutical research communities.

Statement of Work for NIH - NIAAA

Issue Date:

Prepared By:

Quote Number:

Contact Information:

Regional Representative:

Mailing Address:

Our Mission:

About Us:

We discover precise genomic solutions for disease and empower the global biomedical community in our shared quest to improve human health.

JAX® Mice and Research Services are provided as a service to the biomedical community, and in support of the mission of The Jackson Laboratory. For over eighty years, Jackson scientists have been conducting mouse-based biomedical research. As a result, we have accumulated a tremendous wealth of information related to mouse husbandry, breeding, genetics, mutations, biology; mouse model creation methods, technology, techniques and processes; experimental designs and the use of the mouse for translational and genomic research into human diseases ("Mouse Development Information"). Providing JAX® Mice, and support and research technical services at the direction of our clients, enables The Jackson Laboratory to gain new knowledge that is used in our own research and in the development of new mouse models of human disease as well as other research tools.

The contents of this statement of work are confidential and should not be disclosed to any third parties.

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Shawn Hooper Phone: 425-309-3440 E-mail: shawn.hooper@jax.org

Hee-Yong Kim

NIH - NIAAA

Phone:

E-mail: hykim@nih.gov

Q146170

4/29/2022

Milo Careaga

Note: This statement of work expires: 5/29/2022

Copies To:

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

Q146170Quote Number:

mailto:hykim@nih.gov

PROJECT DETAILS & PRICE

Overview:

Gene to be modified: Gt(ROSA)26Sor (ENSMUST00000124246.4) Modification: JAX will insert pCAG-Lox-STOP-Lox-mouse Adgrf1 (ENSMUST00000047399.6)-IRES-tdTomato-bGHpolyA into the mouse ROSA26 locus.

MIJ Strain: C57BL/6J with dual att landing pads (Stock# 036152) Mate Founders to strain: C57BL/6J (Stock# 000664)

Details:

Phase 1: KI plasmid (19-21 weeks)

Milestone 1: Project Design/Reagent Prep (8-10 weeks) A Project Plan will be delivered to the client for approval; throughout the project, you will receive regular project updates. Upon client approval, JAX will proceed with plasmid donor synthesis. This phase-milestone is estimated to be complete 8-10 weeks after client acceptance of the Project Plan.

Milestone 2: Embryo Manipulation (4-5 weeks) Preparation of DNA donor template microinjection mixture and up to 2 embryo manipulations with Bxb1 editing reagents will be attempted to generate putative Founders animals. This phase-milestone is estimated to be 4-5 weeks.

Milestone 3: Founder Identification (4-6 weeks) Sampling of founder generation mice, DNA sequence analysis to validate molecular genome modifications in target gene (short-range PCR/sequence analysis to identify donor DNA integration events, TOPO cloning/sequence analysis (if necessary) to resolve mixed PCR amplicon products). A Founder Report summarizing the results from the CRISPR/Cas embryo manipulation process including DNA sequence analysis of PCR results from the target loci in all live born animals. This phase-milestone is estimated to be 4-6 weeks and clients will be invoiced when Founders are genotyped.

Phase 2: MGS Breeding Service N1 cohort (14-16 weeks)

We will breed founder animals to generate N1 mice with the desired mutation. Once N1 animals are genotyped, clients will receive the N1 Genotyping Report. At this time, animals can be shipped to you or we can provide additional services such as cryopreservation or additional breeding to other JAX strains. Upon delivery of your N1 Report, JAX will hold your mice 2 weeks* free of charge. Standard cage holding charges will be applied after the free holding period. (*4 weeks for international clients.)

This phase is estimated to be 14-16 weeks, and clients will be invoiced when the N1 animals are genotyped.

If JAX is unable to generate the model as agreed upon in the Project Design Plan you will not be

Statement of Work for NIH - NIAAA

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

2Page 8of

Phase 1: CRISPR Service

Weeks 1 - 21

Description Qty Unit Price Total Adjust Ext Total

CRISPR KI plasmid-M1: Design 1.00 $ 9,000.00 $ 0.00 $ 9,000.00

CRISPR KI plasmid-M2: Embryo Manipulation

1.00 $ 11,500.00 $ 0.00 $ 11,500.00

CRISPR KI plasmid-M3: Founder ID 1.00 $ 7,800.00 $ 0.00 $ 7,800.00

Total $ 28,300.00

Phase 2: CRISPR Breeding Service

Weeks 22 - 38

Description Qty Unit Price Total Adjust Ext Total

CRISPR Breeding Service 1.00 $ 4,200.00 $ 0.00 $ 4,200.00

Total $ 4,200.00 charged for the Project. In some cases, the desired genetic modification may result in unanticipated changes in viability, fertility, or morbidity, resulting in the inability to generate a model. JAX does not guarantee that the genetic modification will result in the predicted expression pattern or phenotype even if the modification is performed correctly. Please note that our delivery timelines are estimates only.

Total estimated project time is 33 to 38 weeks.

Timelines are contingent on timely review and approval of the Project Design as described in the Project Plan and communications regarding the project. Delays in communication or delivery of reagents (if applicable) will likely result in additional cost.

DELIVERABLES

The client will receive a Project Plan, Founder Report, N1 Report and a minimum of 2 N1 animals.

The client will receive regular updates on the status of the project, including any substantive project changes and mice with germline transmission of the mutation as described in the Project Plan.

The client will also be provided with a consultation to discuss any additional services and options for your new model.

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

3Page 8of

Phase 3: Sperm Cryopreservation

Weeks 39 - 53

Description Qty Unit Price Total Adjust Ext Total

Sperm Cryopreservation 1.00 $ 875.00 $ -875.00 $ 0.00

Additional Year of Storage - 2023 1.00 $ 0.00 $ 0.00 $ 0.00

Total $ 0.00

SHIPPING

Unless specifically listed in this quotation, cost for shipping is not included in the above total. Shipping cost will vary by destination and will be added as an actual cost at time of shipment.

If importing mice into The Jackson Laboratory, we can assist with importation by having our vendor coordinate your shipment. For your convenience, our negotiated ship rates are:

• All US states: $328 per box

• International: Quoted

CUSTOMER OBLIGATIONS

All Project Design Plans must be approved by the customer prior to starting work on any project.

Untimely communication may result in timeline delays or additional holding expenses.

The contents of this Statement of Work are confidential.

Summary

Description Timeline Weeks

Totals

Phase 1: CRISPR Service 1 - 21 $ 28,300.00

Phase 2: CRISPR Breeding Service 22 - 38 $ 4,200.00

Phase 3: Sperm Cryopreservation 39 - 53

Total $ 32,500.00

Total applied adjustments reflected in the total above = $ -875.00

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

4Page 8of

PROJECT SPECIFICATIONS & IMPORTANT TECHNICAL NOTES

You will receive N1 animals with the mutation described in the Project Design Packet. The Jackson Laboratory does not guarantee the viability or fertility of mutant animals. The investigator will be notified should we encounter issues during the project that could undermine its success.

The project will be maintained in our barrier breeding facility. For a full description of our barrier levels, please see: http://www.jax.org/barrier-levels.

Metal ear tags will be used for individually identifying mice for your project if genotyping is a requirement. Should these metal ear tags interfere with your research, please notify us immediately and The Jackson Laboratory will make alternate arrangements to identify your mice.

Any embryos created from cryopreserved sperm will be heterozygotes of the genotype of the males if homozygous male mice are supplied or heterozygous and wild-type if heterozygous mice are provided.

Some transgenes or genetic mutations may have unanticipated adverse effects on embryonic and fetal development that may result in failure to recover a strain from cryopreserved sperm. This is true even of strains that have demonstrated acceptable fertilization rates through our QC to two-cell embryo production process. THEREFORE, THE JACKSON LABORATORY MAKES NO GUARANTEE THAT LIVE BORN MICE CAN BE RECOVERED. If you require the highest assurance possible that a strain can be recovered, it is strongly recommended that you request our optional Verification of Recoverability Service.

Once the sperm cryopreservation process has been completed, the straws of sperm will be maintained in liquid nitrogen storage in three separate tanks. Two of these storage tanks are located at The Jackson Laboratory in Bar Harbor, Maine and one tank is located off-site.

Customer mice provided to Jackson for performance of service work are and remain the customer’s exclusive property and all information provided by the customer relating to them is treated as confidential and proprietary.

We will provide an annual report, during each year of storage, to you indicating the inventoried number of straws of sperm for each strain cryopreserved.

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

Q146170Quote Number:

5Page 8of http://www.jax.org/barrier-levels

FEES & INVOICING

This cost estimate is based on several assumptions and is an approximation only. This plan does not include the cost of shipping and freight charges. If The Jackson Laboratory needs to create transportation arrangements for strains being shipped to The Jackson Laboratory, the additional freight costs associated with the shipment will be reflected on the invoice. Sales tax is not included in the estimate for goods and services, but will be applied at the time of invoice compliant with State, County and District Tax Codes as The Jackson Laboratory understands applicable to the shipping destination.

***JAX® Services pricing is reviewed annually. At least a thirty (30) day notice will be given on any adjustments.

Payment for services and products rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

ANIMAL HEALTH POLICY

Mice received into The Jackson Laboratory importation facility will be maintained in individually ventilated cages. Due to health status restrictions, once mice are received into our importation facility, they cannot be shipped out of the facility.

In the unlikely event that a biological contamination is confirmed in a JAX® Breeding room, you and your veterinarian will be notified within 48 hours. Please see the following link, http://www.jax.org/agents-monitored for the list of organisms that are excluded from JAX® breeding rooms.

The Jackson Laboratory recommends verification of recovery for strains on the following genetic backgrounds: C57BL/6, FVB/NJ, C3H/HeJ and DBA/2; for hybrid combinations of these strains; and for B6;129 hybrids. For strains on all other genetic backgrounds, verification of recoverability is required and will be included in this price statement of work.

If you request the Verification Recoverability Service for a specific strain of mice when requesting the Sperm Cryopreservation service, then The Jackson Laboratory will attempt to recover live born mice from straws of cryopreserved sperm when we conduct our QC to two-cell process. The Jackson Laboratory will report to you the number of live mice born and the number of embryos transferred. We cannot guarantee that live born mice can be recovered. Note: Genotyping of recovered mice is not included as part of this service. Also, any live born pups born will be euthanized within days of their birth as part of our standard protocol. If you want live born mice to be sent to you, a separate statement of work will be provided for this additional request.

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

Q146170Quote Number:

6Page 8of http://www.jax.org/agents-monitored http://www.jax.org/agents-monitored

CANCELLATION POLICY

Projects cancelled prior to completion as described in this statement of work will incur the following costs:

• All project costs incurred up to the time of the cancellation and associated with project termination.

TERMS AND CONDITIONS

GENERAL

This statement of work is governed by the JAX General Terms and Conditions ("Terms and Conditions") specified on The Jackson Laboratory web site (https://www.jax.org/about-us/legal-information/terms-and-conditions-of-product-use) which are incorporated by reference. These Terms and Conditions have been developed in accordance with The Jackson Laboratory's non-profit mission to improve the quality of human life through discoveries arising from our own genetic research and by enabling the research and education of others. These Terms and Conditions apply to ALL JAX® Services project work conducted by The Jackson Laboratory. Acceptance of this statement of work shall be deemed as agreement to these Terms and Conditions. Furthermore, customers who accept this statement of work represent to the best of their knowledge and belief they have the right to obtain the requested services.

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

Q146170Quote Number:

7Page 8of https://www.jax.org/about-us/legal-information/terms-and-conditions-of-product-use https://www.jax.org/about-us/legal-information/terms-and-conditions-of-product-use

TO ACCEPT THIS STATEMENT OF WORK

By ordering a mouse strain to be created by Jackson using CRISPR/Cas9 technology, you hereby agree to be bound by terms and conditions of the limited use licenses set forth at http://www.jax.org/broadinstitute and https://www.jax.org/cariboubioscience . You also acknowledge and agree that certain Jackson mice or other biological materials may be subject to additional requirements and restrictions, including but not limited to a separate license or other third party approvals, and you hereby agree to comply with these additional requirements and restrictions. Information on additional requirements and restrictions for specific mouse strains can be found on the Mouse Strain Data Sheet for the particular strain at issue and can be searched here: http://www.jax.org/mouse-search. The requirements and restrictions referenced herein are limited to those of which Jackson has knowledge. It is your responsibility to obtain any licenses or third party approvals necessary for the provision of these technical services and/or related deliverables.

FOR MODEL CREATION SERVICES:

Please Sign Where Indicated Below

Send a copy of this fully executed form, along with a purchase order or payment as indicated in the Statement of Work, referencing the Quotation Number and complete billing and shipping information to: JAXServices@jax.org

Client Organization: _________________________________________________________

Client Name (please print): ___________________________________________________

Title: ____________________________________________________________________

Signature: ________________________________________________________________

Date: ____________________________________________________________________

The Jackson Laboratory Designee: Stephen J. Linnell, MBA

Title: Senior Contracts Manager

Signature: ________________________________________________________________

Date: ____________________________________________________________________

The Jackson Laboratory 610 Main Street Bar Harbor, ME 04609

Tel: 1-800-422-6423

(207) 288-6294

E-mail: jaxservices@jax.org

Q146170Quote Number:

8Page 8of http://www.jax.org/broadinstitute https://www.jax.org/cariboubioscience http://www.jax.org/mouse-search mailto:JAXServices@jax.org